What do we know about vaccines and therapeutics?

Table of Contents

1 Effectiveness of drugs being developed and tried to treat COVID-19 patients.

1.0.0.1 Highlights

1.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Wang et al Science in the fight against the novel coronavirus disease
Chin Med J (Engl)
II. Randomized Controlled Trial

They performed a metagenomic analysis of respiratory tract specimens obtained from five patients suffering from the pneumonia in question and identified the virus now known as 2019-nCoV as the causative agent.
Clinical trials are also underway to validate the effectiveness of various other licensed drugs against COVID-19.

As specific therapies targeting 2019-nCoV are lacking, it may be useful to repurpose drugs already licensed for marketing or clinical trials to treat COVID-19 patients in an emergency response; researchers are actively working to identify such drugs.
2020 Wu et al The outbreak of COVID-19: An overview
Journal of the Chinese Medical Association : JCMA
IV. Prevalence Study

Of the 59 suspected cases, 41 patients were confirmed by nextgeneration sequencing or real-time reverse transcription-polymerase chain reaction (RT-PCR).
Antiviral drugs: lopinavir/ritonavir and ribavirin had been tried to treat SARS disease with apparent favorable clinical response.
2020 Wu et al Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP)
J Chin Med Assoc
IV. Prevalence Study

Of the 59 suspected cases, 41 patients were confirmed by nextgeneration sequencing or real-time reverse transcription-polymerase chain reaction (RT-PCR).
Antiviral drugs: lopinavir/ritonavir and ribavirin had been tried to treat SARS disease with apparent favorable clinical response.
2020 Wu et al Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
Acta Pharmaceutica Sinica B
IV. Other The advantages of these therapies are that their metabolic characteristics, dosages used, potential efficacy and side effects are clear as they have been approved for treating viral infections.

For the development of medicines treating SARS-CoV-2, the fastest way is to find potential molecules from the marketed drugs.
2020 Lung Cancer Study Group et al Expert recommendations on the management of patients with advanced non-small cell lung cancer during epidemic of COVID-19 (Trial version)
Zhonghua Jie He He Hu Xi Za Zhi
IV. Other Treatment strategies should be made according to different types of advanced NSCLC patients and efficacy and toxicity of drugs.
2020 YANG et al Current status and progress of 2019 novel coronavirus pneumonia
Chinese Critical Care Medicine
IV. Other Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed.
2020 Xu et al Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV
Viruses
IV. Prevalence Study

Among the 8,866 patients who have been confirmed with COVID-19, nearly half of the patients have been aged 50 years or older (47.7%) .
As effective drugs for SARS, hormones and interferons can also be used to treat COVID-19 .
2020-02-04 Gao et al Machine intelligence design of 2019-nCoV drugs
biorxiv
IV. Other The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.

Finally, the effectiveness of some anti-HIV/AIDS drugs for treating 2019-nCoV is analyzed.
2020-02-04 Long et al The Role of Augmented Intelligence (AI) in Detecting and Preventing the Spread of Novel Coronavirus
J Med Syst
IV. Other AI may be applied to treatment records in order to more quickly home in on the most effective treatment regimens as different approaches are attempted and documented.
2020-02-05 Zhou et al Network-based Drug Repurposing for Human Coronavirus
medrxiv
IV. Other However, all network-predicted repurposable drugs and drug combinations must be validated in preclinical models and randomized clinical trials before being used in patients.
2020-02-20 Arya et al Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs
chemrxiv.org
IV. Other Currently, there are no approved drugs to treat the infection.
2020-02-26 Rothan et al The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak
Journal of Autoimmunity
IV. Other The treatment that have so far been attempted showed that 75 patients were administrated existing antiviral drugs.
2020-02-27 Park et al Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2
biorxiv
IV. Other Currently, researchers put their best efforts to identify effective drugs for COVID-19.
2020-02-27 Fan et al Clinical Features of COVID-19 Related Liver Damage
medrxiv
IV. Other Antiviral therapy can be tried with interferon, lopinavir/litonavir, abidol and dnrunavir.
2020-03-03 Kim et al Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2
biorxiv
IV. Other There is no existing vaccine or proven drug for this disease, but various treatment options, for example utilizing medicines effective in other viral ailments, are being attempted.
2020-03-06 Chen et al Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study
medrxiv
III-3. Time Series Analysis

291 patients with laboratory-confirmed SARS-CoV-2 infection were included in this study.
However, the safety and efficacy of antiviral therapies used in COVID-19 patients need further studied.
2020-03-06 Xu et al Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study
medrxiv
IV. Prevalence Study

Demographic, Epidemiologic, and Baseline Characteristics of the Patients A total of 45 critically ill patients were identified with SARS-CoV-2 infections, the first case included was confirmed on January 14, 2020, and the last one was confirmed on February 20, 2020.
Although antiviral drugs, including osehamivir and ribavirin had been applied to our patients, to date no effective antiviral to treat COVID-19 has been identified.
2020-03-07 Kang et al Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
biorxiv
IV. Other Many ongoing studies are developed to treat COVID-19 232 author/funder.
2020-03-08 Tang et al AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2
biorxiv
IV. Other These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.
2020-03-12 Ge et al A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
biorxiv
IV. Other Those existing drugs with potent antiviral efficacy can be directly applied to treat COVID-19 in a short time, as their safety has been verified in principle in clinical trials.
2020-03-14 MacKenzie et al The hunt for covid-19 drugs
New Scientist
IV. Other Many drugs and vaccines are now being developed and tested
2020-03-14 Ju et al Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase
biorxiv
IV. Other 2b) , was developed by Gilead to treat Ebola virus infections, though not successfully, and is currently in clinical trials for treating COVID-19.
2020-03-15 Zhou et al Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2
Int J Biol Sci
IV. Prevalence Study Currently, several strategies are used in the clinic or under development, such as viral-targeting therapeutics and host-targeting agents (such as interferons, glucocorticoids) for the treatment of COVID-19.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other Direct clinical trials can be conducted among the patients infected with COVID-19 since these drugs are being used for treating other diseases and have well-established safety profiles, making the further evaluation of these drugs much easier.
2020-03-19 Chen et al Clinical progression of patients with COVID-19 in Shanghai, China
Journal of Infection
IV. Prevalence Study

As of Feb 6, 2020, a total of 249 patients were enrolled in this study.
Antiviral drugs (e.g., lopinavir/ritonavir, arbidol) were tried in a small proportion of patients.
2020-03-19 Arshad Ali et al The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat
Journal of Infection and Public Health
III-3. Time Series Analysis

In 2002, a pandemic of SARS occurred endangering the lives of 8098 individuals with a mortality of 774 patients .
Randomized controlled trials are being conducted to evaluate the potential of a combination of lopinavir and ritonavir which showed promising effect against MERS-CoV to treat infected 2019-nCoV patients .
2020-03-19 Driggin et al Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic
Journal of the American College of Cardiology
IV. Prevalence Study

A meta-analysis of six studies inclusive of 1,527 patients with COVID-19 examined the prevalence of CVD and reported the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes to be 17.1%, 16.4%, and 9.7%, respectively .
To date, no approved preventative vaccines or approved therapies are available for COVID-19, although several are being actively studied .
2020-03-20 Favalli et al COVID-19 infection and rheumatoid arthritis: Faraway, so close!
Autoimmunity Reviews
III-3. Time Series Analysis

A population-based study by Doran and colleagues compared two matched groups of 609 patients with or without RA showing that RA patients had a significantly higher risk of serious (RR 1.53, 95% CI 1.41-1.65) and hospitalized (RR 1.88, 95% CI 1.71-2.07) infections .
The need to urgently identify an effective approach to manage COVID-19 led to the strategy of testing the efficacy of the existing antiviral drugs commonly used for other viral infections.
2020-03-20 song et al Advance of Novel Coronavirus Registration Clinical Trial
medrxiv
IV. Prevalence Study Drugs such as lopinavir / ritonavir, interferon, abidol, and chloroquine phosphate can be tried, but their effectiveness needs to be confirmed in clinical studies.In the registration trial, the main treatment was drug therapy, accounting for 68.97%.
2020-03-21 Rismanbaf et al Potential Treatments for COVID-19; a Narrative Literature Review
Arch Acad Emerg Med
III-3. Time Series Analysis

Also, according to Jian-ya et al., treatment of 51 COVID-19 patients with traditional Chinese medicine, interferon, Lopinavir, Ritonavir and short-term (3 to 5 days) corticosteroids was successful and resulted in recovery and discharge of 50 patients .
Apparently, in addition to the drugs currently prescribed to treat COVID-19, Arbidol hydrochloride, interferon, and Thalidomide plus Methylprednisolone can also be used due to their effects reported in clinical studies.
2020-03-23 Duan et al The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study
medrxiv
II. Randomized Controlled Trial

The neutralizing antibody titers of five patients increased and four patients remained atthe same level after CP transfusion.SARS-CoV-2 RNA, assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), was positive in seven patients and negative in three cases before CP transfusion.
All patients received antiviral treatment despite the uncertainty of the efficacy of drugs used.
2020-03-23 Rios et al Effectiveness and safety of antiviral or antibody treatments for coronavirus
medrxiv
III-2. Matched Case Control

The four cases reports/series 29,45,46,48 that included immunosuppressed patients with MERS (5 patients) and unspecified coronavirus (2 patients) reported 3 deaths all in patients with hematological malignancies treated with foscarnet (n=1) and oseltamivir (n=2).
Overall the results of the included studies proved inconclusive on the effectiveness of antiviral drugs in treating coronavirus infections and prevent any particular treatments from being recommended for use.
2020-03-24 Yu et al Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study
The Lancet Infectious Diseases
IV. Other Although remdesivir and other antiviral drugs have been used in the clinical treatment of patients with COVID-19, no data of their safety and efficacy as COVID-19 treatments have been published.
2020-03-25 Marmor et al COVID-19 and Chloroquine/Hydroxychloroquine: is there Ophthalmological Concern?
American Journal of Ophthalmology
IV. Other (HCQ) are generic antiviral agents that have shown effectiveness against SARS virus, and in this time of pandemic, physicians are trying any plausible approach to therapy.
2020-03-26 Singh et al Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries
Diabetes & Metabolic Syndrome: Clinical Research & Reviews
IV. Other Abstract Background and aims No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried.

No drugs are currently approved for Coronavirus Disease-2019 (COVID- 19) , although some have been tried.

Reports gathered so far have suggested that a number of drugs could be potential candidates for the treatment of COVID-19, although the clinical effectiveness of these drugs have not yet been fully evaluated.
2020-03-26 ul Qamar et al Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants †
Journal of Pharmaceutical Analysis
IV. Other Recent 167 drug repurposing studies proposed few drugs that target SARS-CoV-2 3CL pro and suggested that 168 they could be used to treat COVID-19.
2020-03-27 Wang et al Elevated serum IgM levels indicate poor outcome in patients with coronavirus disease 2019 pneumonia: A retrospective case-control study
medrxiv
IV. Prevalence Study

Further, a paired case-control study was conducted where each deceased case was matched to three mild-moderate patients of similar age.
Effective strategies to treat this disease are urgently needed, but no drugs have been proven to be effective for the treatment of COVID-19 pneumonia 4 .
2020-03-30 Fan et al Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study
medrxiv
IV. Other No effective antiviral drugs that treat COVID-19 have been identified to date, and opinions on whether antiviral drugs should even be used to treat COVID-19 differ.
2020-03-30 Beck et al Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model
Computational and Structural Biotechnology Journal
IV. Other Although much intensive effort is being made worldwide to develop drugs or vaccines for SARS-CoV-2, patients currently suffering from COVID-19 cannot expect benefits from them due to the slow development process of novel drugs or vaccines.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model So far, the most common therapies tried in patients with CoVs are ribavirin, lopinavir/ritonavir, IFN, or their combinations .

In addition to the drug regimens used in patients, numerous drugs developed for the treatment of infection with CoVs were thoroughly discussed in the literature .
2020-03-31 Milewska et al HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV
biorxiv
IV. Other 76 Currently, there are no vaccines or drugs with proven efficacy to treat coronavirus 77 infection, and treatment is limited to supportive care.
2020-03-31 Ling et al Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2)
Journal of Integrative Medicine
IV. Other It was recommended that potential vaccines and antiviral medicines should be developed.
2020-03-31 Wang et al COVID-19 in Hemodialysis Patients: A Report of 5 Cases
American Journal of Kidney Diseases
IV. Other There are no antiviral drugs of proven efficacy or applicable vaccines.
2020-04-01 Xu et al Traditional Chinese Medicine treatment of COVID-19
Complementary Therapies in Clinical Practice
IV. Other These two prescriptions can be used to treat patients with mild infection of COVID-19.

2 Clinical and bench trials to investigate less common viral inhibitors against COVID-19 such as naproxen, clarithromycin, and minocyclinethat that may exert effects on viral replication.

2.0.0.1 Highlights

2.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Andersen et al Discovery and development of safe-in-man broad-spectrum antiviral agents
International Journal of Infectious Diseases
IV. Other Moreover, structure-activity relationship analysis of BSAAs suggest that some agents, such as doxycycline, artesunate, omeprazole, nitazoxanide, suramin, azithromycin, minocycline and chloroquine, could have novel antibacterial, antiprotozoal, antifungal or anthelmintic activities (Figure 4 ).
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
The efficacy of niclosamide as an inhibitor of virus replication was proven in several assays.
2020-02-03 Lin et al Molecular Modeling Evaluation of the Binding Effect of Ritonavir, Lopinavir and Darunavir to Severe Acute Respiratory Syndrome Coronavirus 2 Proteases
biorxiv
IV. Other It is suggested that the therapeutic effect of ritonavir and lopinavir on COVID-19 may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.

In conclusion, the therapeutic effect of ritonavir and lopinavir on COVID-19 and other coronavirus disease may be mainly due to their inhibitory effect on CEP_C30, while ritonavir may have stronger efficacy; the inhibitory effect of darunavir on SARS-CoV-2 and its potential therapeutic effect may be mainly due to its inhibitory effect on PLVP.
2020-02-04 Wang et al Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Cell Res
IV. Other Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo.
2020-02-10 Arabi et al Critical care management of adults with community-acquired severe respiratory viral infection
Intensive Care Med
II. Randomized Controlled Trial

The importance of timing of oseltamivir treatment has been demonstrated in an observational study of 1950 patients admitted to ICUs with influenza A(H1N1) pdm09, which showed a trend toward improved survival for those treated earliest .
In an open-label RCT of hospitalized patients with influenza (n = 107), early combination therapy with clarithromycin, naproxen, and oseltamivir was associated with reduced mortality and hospital length of stay compared to oseltamivir monotherapy .

A study of clarithromycin combined with the cyclooxygenase inhibitor flufenamic acid in hospitalized patients with influenza is underway (NCT03238612).

Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs.

As summarized below, those that have progressed to clinical study include macrolides, corticosteroids, cyclo-oxygenase2 inhibitors, mTOR inhibitors like sirolimus, statins, and high-dose vitamin C. However, until further evidence becomes available, these agents should not be used for managing severe RVIs unless there is another indication or as part of a clinical trial.
2020-02-11 Tang et al An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov)
Infect Dis Model
IV. Other Anti-retroviral drugs belonging to the class of protease inhibitors, including Lopinavir and Ritonavir, usually utilized for the treatment of HIV/AIDS patients, seem to exert anti-viral effects against coronaviruses.
2020-02-27 Fan et al Clinical Features of COVID-19 Related Liver Damage
medrxiv
IV. Other In this study, the drugs used by patients before admission are mainly antibacterial drugs (including moxifloxacin, cephalosporins), antiviral drugs (abidol, oseltamivir, acyclovir), and antipyretic drugs with acetaminophen.

The medications of COVID-19 patients before admission included antibiotics (Levofloxacin, Azithromycin, Cephalosporin), antiviral drugs (Arbidol, Oseltamivir, Acyclovir)and conventional febrifuge (Ibuprofen).
2020-03-02 Ko et al Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
biorxiv
IV. Other Especially the cardiotonic drugs ouabain, digitoxin, or digoxin with a TI greater than 100 in monotherapy or combined with remdesivir, a drug that is currently in clinical trials for the treatment of COVID-19, or with other therapeutics, might lead to drug synergism.
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
The anti-viral drug remdesivir (Gilead®) is in clinical trials to treat COVID-19 in Wuhan .

The antiviral efficiency of five FAD-approved drugs and two well-known broadspectrum antiviral drugs have been studied and it has been found that remdesivir and chloroquine effectively inhibit SARS-CoV-2 in vitro .
2020-03-06 Zhang et al Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China
medrxiv
III-2. Cross Sectional Control

The study population included a total of 221 admitted patients with confirmed COVID-19 infection in Zhongnan Hospital of Wuhan University, between January 2, 2019 and and 62 (28.1%), respectively.
30 Now a couple of clinical trials focus on the efficacy of remdesivir, as well as other therapeutic strategies, such as immunoglobulins, Vitamin C infusion, mesenchymal stem cell treatment, arbidol hydrochloride plus interferon atomization, ritonavir combined with oseltamivir, lopinavir plus ritonavir and arbidol hydroxychloroquine and methylprednisolone.
2020-03-11 Zhou et al Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
The Lancet
III-2. Retrospective Cohort

Before Jan 11, 2020, SARS-CoV-2 RNA detection results were not available in the electronic medical records, from which data for this study were obtained retrospectively; therefore, this study includes 29 of the 41 patients originally reported on.
Ran domised clinical trials for lopinavir/ ritonavir (ChiCTR2000029308) and intravenous remdesivir (NCT04257656, NCT04252664) in treatment of COVID-19 are currently in progress.
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other These compounds appeared to exhibit good enzyme-inhibiting activity (pIC 50 ≈ 7 Ritonavir is a pharmacokinetic profile enhancer that may potentiate the effects of other protease inhibitors due to its ability to attenuate the degradation of those drugs by the liver enzyme CYP3A4 and thus is used in combination with antivirial Lopinavir.
2020-03-12 Matsuyama et al The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
biorxiv
IV. Other Ciclesonide and mometasone suppressed viral replication with a similar efficacy to lopinavir (Fig.
2020-03-13 Baron et al Teicoplanin: an alternative drug for the treatment of COVID-19?
International Journal of Antimicrobial Agents
IV. Other Chloroquine, remdesivir, lopinavir, ribavirin and ritonavir have shown efficacy to inhibit coronavirus in vitro.

In this context, other drugs also showed significant efficacy against SARS-Cov-2 in vitro, including remdesivir, lopinavir, ribavirin and ritonavir ( ) .
2020-03-13 Berra et al Protocol for a randomized controlled trial testing inhaled nitric oxide therapy in spontaneously breathing patients with COVID-19
medrxiv
II. Randomized Controlled Trial

Based on results reported in Table 2 , the same step could then be repeated increasing sample size from 340 to 500 patients, from 500 patients to 760 and from 760 patients to 1260.
At the present time, there are no proven etiological treatments for COVID-19 but some ongoing clinical trials are testing the effects of anti-viral drugs (NCT04252664 on ClinicalTrials.gov).
2020-03-14 Ju et al Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase
biorxiv
IV. Other Anti-viral drug design based on this principle may lead to potent viral polymerase inhibitors with fewer side effects.
2020-03-15 Zheng et al SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat
Int J Biol Sci
IV. Other To search for an antiviral drug effective in treating SARS-CoV-2 infection, Wang and colleagues evaluated seven drugs, namely, ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, remdesivir (GS-5734) and favipiravir (T-750) against the infection of SARS-CoV-2 on Vero E6 cells in vitro .
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other Furthermore, RNA synthesis inhibitors (like 3TC, TDF), remdesivir, neuraminidase inhibitors, peptide (EK1), anti-inflammatory drugs, abidol, Chinese traditional medicine, such as Lianhuaqingwen and ShuFengJieDu Capsules, could be the promising COVID-19 treatments.

2 Recently, the in vitro antiviral efficacy of approved drugs such as ribavirin, penciclovir, nitazoxanide, nafamostat, and chloroquine was compared with that of the two broad-spectrum antiviral drugs remdesivir and favipiravir for COVID-19.

75 The same two protease inhibitors lopinavir and ritonavir, when combined with ribavirin, were found to be associated with favorable clinical responses in SARS patients indicating therapeutic efficacy.

63 The study also pointed out that the three nucleoside analogs such as ribavirin, penciclovir, and favipiravir may not have significant in vivo antiviral effects against COVID-19 since higher concentrations were required to reduce the viral infection in vitro.
2020-03-19 Arshad Ali et al The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat
Journal of Infection and Public Health
III-3. Time Series Analysis

In 2002, a pandemic of SARS occurred endangering the lives of 8098 individuals with a mortality of 774 patients .
Randomized controlled trials are being conducted to evaluate the potential of a combination of lopinavir and ritonavir which showed promising effect against MERS-CoV to treat infected 2019-nCoV patients .
2020-03-20 Jeon et al Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
biorxiv
IV. Other Among the 48 drugs that were evaluated in our study, 24 drugs showed potential antiviral activities against SARS-CoV-2 with IC 50 values in between 0.1 and 10 µM; Tilorone, Cyclosporine, Loperamide, Mefloquine, Amodiaquine, Proscillaridin, Digitoxin, Digoxin, Hexachlorophene, Hydroxyprogesterone caproate, Salinomycin, Ouabain, Cepharanthine, Ciclesonide, Oxyclozanide, Anidulafungin, Gilteritinib, Berbamine, Tetrandrine, Abemaciclib, Ivacaftor, Bazedoxifene, Niclosamide, and Eltrombopag.

In particular, the effect of favipiravir and atazanavir was compared to those of the reference drugs (chloroquine, lopinavir, remdesivir) because favipiravir is considered as a drug candidate for clinical trials and atazanavir was recently predicted as the most potent antiviral drug by AI-inference modeling 13 .
2020-03-20 Runfeng et al Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)
Pharmacological Research
IV. Other Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)
2020-03-20 GAUTRET et al Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial
medrxiv
IV. Other A recent paper reported an inhibitor effect of remdesivir (a new antiviral drug) and chloroquine (an old antimalarial drug) on the growth of SARS-CoV-2 in vitro, and an early clinical trial conducted in COVID-19 Chinese patients, showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance, when comparing to controls groups .
2020-03-20 Gautret et al Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
International Journal of Antimicrobial Agents
IV. Other A recent paper reported an inhibitor effect of remdesivir (a new antiviral drug) and chloroquine (an old antimalarial drug) on the growth of SARS-CoV-2 in vitro, and an early clinical trial conducted in COVID-19 Chinese patients, showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance, when comparing to controls groups .
2020-03-23 Shaman et al Initial Simulation of SARS-CoV2 Spread and Intervention Effects in the Continental US
medrxiv
IV. Other As a derivative of CQ, hydroxychloroquine (HCQ) has similar therapeutic effects and fewer adverse effects.
2020-03-29 Kang et al Recent Progress in understanding 2019 Novel Coronavirus associated with Human Respiratory Disease: Detection, Mechanism and Treatment
International Journal of Antimicrobial Agents
IV. Prevalence Study In vitro, chloroquine can enhance the effects of other antiviral drugs 34 .

In addition, combination therapies of interferon with other antiviral drugs have been used to treat SARS or MERS patients and show synergistic effects 60, 74 .
2020-03-29 Li et al Coronavirus disease 2019 (COVID-19): current status and future perspective
International Journal of Antimicrobial Agents
III-2. Retrospective Cohort

Analysis of the first 99 confirmed cases of SARS-CoV2 infection revealed that cytokine storm syndromes occurred in patients with severe COVID-19 and 17 (17%) had ARDS and, among them, 11 (11%) patients deteriorated within a short period of time and died of multiple organ failure .
This suggests that lopinavir-ritonavir may exert an antiviral effect by inhibiting the protein synthesis of the SARS-CoV2.
2020-03-30 Kapoor et al Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review
medrxiv
I. Systematic Review

Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review.
The immune-modulating activity of CQ may also synergistically enhance its antiviral effect in vivo.
2020-03-30 Chen et al Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
medrxiv
IV. Other As a derivative of CQ, hydroxychloroquine (HCQ) has similar therapeutic effects and fewer adverse effects.
2020-03-31 Wu et al SARS-CoV-2, COVID-19 and inherited arrhythmia syndromes
Heart Rhythm
IV. Prevalence Study

In the afore-mentioned study 93 of 138 hospitalized COVID-19 patients, arrhythmia (not further specified) was reported in 17% 6 of total patients and in 16 of 36 patients admitted to the ICU.
24 However, 149 both chloroquine and hydroxychloroquine are metabolised by CYP3A4, and COVID-19 150 treatment with (hydroxy)chloroquine can be combined with additional anti-viral treatments 9 such as ritonavir plus lopinavir (both potent CYP3A4 inhibiting drugs; their combination is 152 associated with QT-prolongation), azithromycin (besides a macrolide antibiotic also 153 investigated for its antiviral properties, with also (weak) CYP3A4 inhibition and associated 154 with QT-prolongation) 25,26 , or remdesivir (an investigational drug for which metabolism and 155 possible QT prolonging effects are not yet resolved).
2020-03-31 Sodhi et al Safety of Ibuprofen in Patients with COVID-19; Causal or Confounded?
Chest
IV. Other If acetaminophen alone cannot achieve its antipyretic effect, the current evidence is not sufficient to advise against coadministration of ibuprofen with acetaminophen, although risk of adding ibuprofen should still be assessed against its benefits.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model Despite the antiviral activity observed with in vitro studies, the clinical effect was not consistent , in that ribavirin does not prolong the survival of SARS-CoV patients , while lopinavir/ritonavir plus ribavirin seemed to improve clinical outcomes for SARS patients , but the improvement was not confirmed in MERS-CoV patients.
2020-03-31 Deretic et al Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells
biorxiv
IV. Other Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells
2020-03-31 Lai et al Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
International Journal of Antimicrobial Agents
IV. Other Several potential drug candidates, including lopinavir/ritonavir (Kaletra R ), nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (Arbidol R ), DNA synthesis inhibitors (such as tenofovir disoproxil and lamivudine), chloroquine and Chinese traditional medicines (such as ShuFeng JieDu or Lianhua Qingwen capsules), have been proposed .
2020-03-31 Li et al The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future
Microbes and Infection
IV. Prevalence Study

11 January 2020 41 patients have been diagnosed to have infection of the novel coronavirus, with 763 close contacts, 7 severe cases and the first death.
Other antiviral drugs, like FAD-approved drugs including ribavirin, penciclovir, nitrazine, nalfamusta, chloroquine, and the two broad-spectrum antiviral drugs redexivir (GS-5734) and favivir (T-705), are being evaluated by measuring the effects of these compounds on cytotoxicity, virus yield and infection rate of 2019-nCoV.
2020-05-31 Zhang et al The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China
Clinical Immunology
II. Randomized Controlled Trial

One study analyzed the lymphocyte subsets and cytokines in 123 patients, all patients had lymphcytopenia, The percentage of CD8 + T cell reduction were 28.43% and 61.9% in mild and severe group respectively, and the NK cell reduction were 34.31% and 47.62% respectively,in mild and severe groups.
Although CQ or HCQ are frequently used for the treatment of rheumatic diseases due to its immunomodulatory and anti-inflammatory effects, the benefit in treating COVID-19 may be mainly attributed to its anti-viral effects.
2020-06-30 Gupta et al Clinical considerations for patients with diabetes in times of COVID-19 epidemic
Diabetes & Metabolic Syndrome: Clinical Research & Reviews
IV. Other In the absence of a specific antiviral drug, anecdotal use of drugs like lopinavir, ritonavir, interferon-1b, RNA polymerase inhibitor remdesivir, and chloroquine has been reported.
2020-07-31 Shereen et al COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses
Journal of Advanced Research
IV. Prevalence Study

In 2001 the samples were isolated from the healthy persons of Hongkong and the molecular assessment showed 2.5% frequency rate of antibodies against SARS-coronavirus.
Nafamostat, Nitazoxanide, Ribavirin, Penciclovir, Favipiravir, Ritonavir, AAK1, Baricitinib, and Arbidol exhibited moderate results when tested against infection in patients and in-vitro clinical isolates .

However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery.

3 Methods evaluating potential complication of Antibody-Dependent Enhancement (ADE) in vaccine recipients.

3.0.0.1 Highlights

3.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Du et al Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
Frontiers in Microbiology
III-3. Time Series Analysis Moreover, immunization with a recombinant MERS-CoV NTD protein (rNTD) can induce neutralizing antibodies and cellmediated responses, protecting Ad-hDPP4-transduced mice against MERS-CoV challenge (Jiaming et al., 2017) .

In addition, MERS-CoV S1 protein adjuvanted with Advax and Sigma Adjuvant System induced low-titer neutralizing antibodies in dromedary camels with reduced and delayed viral shedding after MERS-CoV challenge, but high-titer neutralizing antibodies in alpacas with complete protection of viral shedding from viral infection, indicating that protection of MERS-CoV infection is positively correlated with serum neutralizing antibody titers (Adney et al., 2019) .

For example, while a MERS-CoV RBD subunit vaccine (S377-588 protein fused with Fc) alone induced detectable neutralizing antibody and T-cell responses in immunized mice, inclusion of an adjuvant enhanced its immunogenicity.
2020-02-14 Cui et al Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins
biorxiv
IV. Other An important target for vaccines and drugs is the surface (S) protein which has been evaluated in SARS-CoV and MERS-CoV with an idea that a neutralizing antibody targeting wS protein could provide passive immunity for 2019-nCoV .

Thus, wS remains the important target for vaccines and drugs previously evaluated in SARS and MERS while a neutralizing antibody targeting the wS protein could provide passive immunity .
2020-02-21 Wang et al A novel coronavirus outbreak of global health concern
The Lancet
IV. Prevalence Study

3 In The Lancet, Chaolin Huang and colleagues 7 report clinical features of the first 41 patients admitted to the designated hospital in Wuhan who were confirmed to be infected with 2019-nCoV by Jan 2, 2020.
Future animal model and clinical studies should focus on assessing the effectiveness and safety of promising antiviral drugs, monoclonal and polyclonal neutralising anti body products, and therapeutics directed against immunopathologic host responses.
2020-02-24 Rasmussen et al Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know
American Journal of Obstetrics and Gynecology
IV. Other Whether these gastrointestinal complications were related to 166 complications from SARS or its treatment or if they were secondary to preterm delivery is 167 unknown.
2020-02-27 Shang et al Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy
biorxiv
IV. Other VDR, ATG16L1 and NF-κB p65 were modified to investigate the alteration of AS’s effect on pro-inflammatory cytokines release, bacteria clearance and autophagy activities in sepsis-induced immunosuppression.Key ResultsAS significantly reduced the mortality of cecal ligation and puncture (CLP)-induced sepsis immunosuppression mice challenged with Pseudomonas Aeruginosa, and enhanced proinflammatory cytokines release and bacterial clearance to reverse sepsis-induced immunosuppression in vivo and in vitro.

Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy
2020-02-27 Herst et al An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design
biorxiv
IV. Other This suggests that a CTL vaccine may be more effective for prophylaxis against filovirus protection than an antibody vaccine if the anticipated route of EBOV exposure is via aerosol.
2020-03-07 Kang et al Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
biorxiv
IV. Other Because mutant viruses in the S protein is prone to escape the targeted therapeutic with 55 different host-cell receptor binding patterns 4 , as well as antibody-dependent enhancement 56 (ADE) effects of S protein antibodies are found in MERS coronavirus 5 , there are several limitations 57 on targeting S protein for antiviral approaches.
2020-03-10 Ibrahim et al COVID-19 spike-host cell receptor GRP78 binding site prediction
Journal of Infection
IV. Other Inhibition of protein synthesis and enhancement of the refolding is the end result of the enzymes' activation.
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other An engineered ectodomain immunogen (soluble S protein), in combination with the emulsion adjuvant, GSK2, induced high levels of anti-SARS-CoV IgG2a or IgG2b antibody responses and neutralizing antibody responses in animal models.
2020-03-13 Qiao et al What are the risks of COVID-19 infection in pregnant women?
The Lancet
IV. Other Previous studies have shown that SARS during pregnancy is associated with a high incidence of adverse maternal and neonatal complications, such as spontaneous miscarriage, preterm delivery, intrauterine growth restriction, application of endotracheal intu bation, admission to the intensive care unit, renal failure, and disseminated intravascular coagulopathy.
2020-03-14 Bao et al Reinfection could not occur in SARS-CoV-2 infected rhesus macaques
biorxiv
III-3. Time Series Analysis

229 The nasal/throat/anal swab samples and mainly tissue compartments collected from 230 infected monkeys were tested for SARS-CoV-2 RNA by quantitative real-time reverse 231 author/funder.
It has been reported that the high levels of neutralizing antibodies have a protective 107 effect on SARS-CoV infection, but the low neutralizing antibody are more susceptible 108 to enhance the SARS-CoV infection and trigger antibody-dependent enhancement 109 (ADE) effect 6 .

In this study, ADE were not found in infected monkeys that were subsequently exposed 113 to SARS-CoV-2.
2020-03-15 Yi et al COVID-19: what has been learned and to be learned about the novel coronavirus disease
Int J Biol Sci
IV. Prevalence Study

On February 11, 2020, a multi-center study on 8,866 patients including 4,021 confirmed COVID-19 patients presented a more updated illustration of the epidemic as follows ( UlBi-HX_rHPXa1qHA2bhdA).
However, the in vivo efficacy of these vaccine candidates in elderly individuals and lethal-challenge models and their protection against zoonotic virus infection have yet to be determined before a clinical study is initiated.
2020-03-16 Borenstein et al Ginkgolic acid inhibits fusion of enveloped viruses
Sci Rep
IV. Other In vivo experiments in an animal model are needed to assess the actual therapeutic antiviral effect and cytotoxicity of GA.
2020-03-17 Li et al Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation
biorxiv
IV. Other In addition to potent neutralizing antibody elicitation upon immunization, potential 315 antibody-dependent disease enhancement (ADE) is the major concern for an efficacious The copyright holder for this preprint (which was not peer-reviewed) is the .
2020-03-17 Lv et al Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections
biorxiv
III-3. Time Series Analysis

In this study, we examined the 69 antibody responses in 15 patients from Hong Kong who were infected by SARS-CoV-2, 70 and seven by SARS-CoV.
Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other A safety concern for passive immunization with antibodies is a possible antibody-dependent enhancement (ADE) of virus replication.
2020-03-19 Driggin et al Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic
Journal of the American College of Cardiology
IV. Prevalence Study

A meta-analysis of six studies inclusive of 1,527 patients with COVID-19 examined the prevalence of CVD and reported the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes to be 17.1%, 16.4%, and 9.7%, respectively .
Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism.
2020-03-20 Yang et al Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study
medrxiv
III-2. Retrospective Cohort

In a study of 52 critically ill patients in Wuhan, 32 (61.5%) patients died at 28 days and the mortality rate was 81.1% (30/37) in patients requiring mechanical ventilation.
32, 33 Second, it was reported that antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses might also be involved in COVID-19.

ADE can elicit sustained inflammation, lymphopenia, and/or cytokine storm, which makes it a possible explanation for the geographic limitation of severe cases.
2020-03-20 OKBA et al SARS-CoV-2 specific antibody responses in COVID-19 patients
medrxiv
III-3. Time Series Analysis

All three COVID-19 patients had reactive antibodies by both the IgG (6/10 serum samples) and IgA (7/10 serum samples) ELISAs (Figure 3) .
(F) Virus neutralizing antibodies were tested using the plaque reduction neutralization assay (PRNT).
2020-03-20 Nickbakhsh et al Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence
medrxiv
IV. Prevalence Study

Of 74,241 patient episodes of respiratory illness with sCoV subtyping, 8,912 patients experienced multiple episodes over the study timeframe.
Immunosenescence may exacerbate low levels of protective immunity in the elderly .
2020-03-20 Sominsky et al One size does not fit all – Patterns of vulnerability and resilience in the COVID-19 pandemic and why heterogeneity of disease matters
Brain, Behavior, and Immunity
IV. Prevalence Study In addition to children, pregnant women also represent a vulnerable population at risk for viral infections, with increased risk of complications in influenza, including the 2009 influenza H1N1 pandemic (Siston et al., 2010) , varicella virus, measles and the severe foetal consequences of Zika virus (reviewed in (Racicot and Mor, 2017) ).
2020-03-21 Ong et al COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning
biorxiv
IV. Prevalence Study However, passive transfer of anti-NS1 252 antibody or immunization with NS1 conferred protection 38 .
2020-03-23 Zhang et al COVID-19: Melatonin as a potential adjuvant treatment
Life Sciences
II. Randomized Controlled Trial

A recent meta-analysis of a total of 22 randomized controlled trials suggested that a supplementary use of melatonin is associated with a significant reduction of TNF-α and IL-6 level .
It was also reported that melatonin had benefits in patients with myocardial infarction, cardiomyopathy, hypertensive heart diseases and pulmonary hypertension, and probably functions via the TLR4/survivor activating factor enhancement pathway .
2020-03-23 Duan et al The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study
medrxiv
II. Randomized Controlled Trial

The neutralizing antibody titers of five patients increased and four patients remained atthe same level after CP transfusion.SARS-CoV-2 RNA, assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), was positive in seven patients and negative in three cases before CP transfusion.
Moreover, the corticosteroid treatment for COVID-19 lung injury remains controversial, due to delayed clearance of viral infection and complications .
2020-03-25 Ren et al EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS OF HEART TRANSPLANT RECIPIENTS DURING THE 2019 CORONAVIRUS OUTBREAK IN WUHAN, CHINA: A DESCRIPTIVE SURVEY REPORT
The Journal of Heart and Lung Transplantation
IV. Prevalence Study

There are 63 men and 24 women, average age is 51±12 years, 80 (92.0%) of them lived together with relatives, the number of relatives ranged from 1 to 8.
21.3% recipients had pre-existing lymphopenia and 87.2% of recipients had therapeutic tacrolimus concentration (5-12ng/ml).
2020-03-26 Zhang et al A Multicentre Study of 2019 Novel Coronavirus Disease Outcomes of Cancer Patients in Wuhan, China
medrxiv
III-2. Retrospective Cohort

Among those 23 patients, 9 cases were receiving chemotherapy-based comprehensive therapies, 7 cases were during perioperative period, 3 cases were receiving supportive treatment, 2 cases were receiving radiotherapy combined with targeted therapy or with endocrinotherapy, and the rest 2 patients were receiving endocrinotherapy or immunotherapy.
proportion of all cancers; 10 cases lung cancer patients were ongoing anticancer treatment, and they may have high risks of nosocomial infection and low immunity to SARS-CoV viral particles.
2020-03-27 Giovannoni et al The COVID-19 pandemic and the use of MS Disease-Modifying Therapies
Multiple Sclerosis and Related Disorders
IV. Prevalence Study

Reassuringly, five patients on natalizumab infected with dengue virus cleared the virus without complications similar to those on fingolimod (Fragoso et al., 2016b) .
Reassuringly, five patients on natalizumab infected with dengue virus cleared the virus without complications similar to those on fingolimod (Fragoso et al., 2016b) .
2020-03-27 Zheng et al Risk-adapted Treatment Strategy For COVID-19 Patients
International Journal of Infectious Diseases
IV. Other However, critical influenza may also cause complications with high morbidity and mortality, such as pneumonia, myocarditis, central nervous system disease and death .
2020-03-29 Li et al Coronavirus disease 2019 (COVID-19): current status and future perspective
International Journal of Antimicrobial Agents
III-2. Retrospective Cohort

Analysis of the first 99 confirmed cases of SARS-CoV2 infection revealed that cytokine storm syndromes occurred in patients with severe COVID-19 and 17 (17%) had ARDS and, among them, 11 (11%) patients deteriorated within a short period of time and died of multiple organ failure .
Human NK cells lyse antibody-coated virus-infected cells via the process of antibody-dependent cellular cytotoxicity (ADCC) .
2020-03-29 Woolley et al Dilemma of Organ Donation in Transplantation and The COVID-19 Pandemic
The Journal of Heart and Lung Transplantation
III-2. Retrospective Cohort

One report of two cases of COVID-19 in heart transplant recipients in China suggested that the disease was manifest in a manner similar to that expected in the general population and did not progress into the hyperinflammation stage of the disease with recovery in both cases.
All potential recipients should also be tested for COVID-19 prior to transplantation.
2020-03-31 Tetro et al Is COVID-19 receiving ADE from other coronaviruses?
Microbes and Infection
IV. Other One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses.

Should ADE be proven to be a mechanism of pathogenesis, both treatment regimens and vaccine development will need to take this phenomenon into consideration to ensure it is mitigated and in the case of a vaccine, avoided altogether.

Individuals suffering the most may have been primed by one or more prior coronavirus exposures, and due to antigenic epitope heterogeneity, are experiencing the effects of antibody dependent enhancement (ADE).

Although prior SARS-CoV exposure or infection may play a role in ADE, it likely is not be the predominant priming virus.

ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model Most importantly, RBD-based vaccine could induce neutralizing antibody responses and protection against SARS-CoV infection in the immunized animals, while it did not elicit ADE or other harmful immune responses, unlike the virusinactivated vaccines or full-length S protein-based vaccines as discussed above.
2020-03-31 Tuech et al Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic
Journal of Visceral Surgery
IV. Prevalence Study

This prospective trial included 1421 patients, and mortality at 3 months was 6.3%.
After total gastrectomy, rates of major complications are lower, but still 10-15%, mostly respiratory and septic complications .
2020-03-31 Xu et al Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
can cause invasive disease in eculizumab recipients 1 , 3 , 4 and eculizumab recipients are at an estimated 20 0 0-fold increased risk of meningococcal disease (caused by Neisseria meningitidis ).
2020-03-31 Haixu et al Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
can cause invasive disease in eculizumab recipients 1 , 3 , 4 and eculizumab recipients are at an estimated 20 0 0-fold increased risk of meningococcal disease (caused by Neisseria meningitidis ).
2020-03-31 Tang et al Emergence of a novel coronavirus causing respiratory illness from Wuhan, China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
can cause invasive disease in eculizumab recipients 1 , 3 , 4 and eculizumab recipients are at an estimated 20 0 0-fold increased risk of meningococcal disease (caused by Neisseria meningitidis ).
2020-03-31 Wang et al Emergence of SARS-like coronavirus poses new challenge in China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
can cause invasive disease in eculizumab recipients 1 , 3 , 4 and eculizumab recipients are at an estimated 20 0 0-fold increased risk of meningococcal disease (caused by Neisseria meningitidis ).
2020-04-01 Xie et al Insight into 2019 novel coronavirus — an updated intrim review and lessons from SARS-CoV and MERS-CoV
International Journal of Infectious Diseases
IV. Prevalence Study The available observational studies and meta-analysis of corticosteroid treatment suggested impaired antibody response, increased mortality and secondary infection rates in influenza, increased viraemia and impaired virus clearance of SARS-CoV and MERS-CoV, and complications of corticosteroid therapy in survivors (Zumla et al., 2020) .
2020-06-30 Liu et al Why are pregnant women susceptible to COVID-19? An immunological viewpoint
Journal of Reproductive Immunology
IV. Prevalence Study

A total of eighteen pregnant women infected with NCP (mean age: 30 years) had one or two common clinical symptoms, such as fever, cough, cholecystitis, sore throat, and diarrhea.
ADE can cause sustained inflammation, lymphopenia, and cytokine storm, and one or all of which happened in the reported severe cases and deaths (Tetro, 2020) .

Moreover, there was significant discrepancy of serious cases and deaths happened between the areas within Hubei Province and the rest of the world, which may be possibly explained by antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to similar antigenic epitopes with other coronaviruses.

4 Exploration of use of best animal models and their predictive value for a human vaccine.

4.0.0.1 Highlights

4.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Ralph et al 2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness
Journal of Infection in Developing Countries
IV. Prevalence Study

On 8 January 2020, it was reported that a novel coronavirus had been sequenced from one patient and subsequently identified in some of the other patients with pneumonia , later reported as 15 of the 59 patients .
As vaccine candidates are identified, the requirement of animal models for vaccine development and evaluation will be essential.
2020 Wu et al The outbreak of COVID-19: An overview
Journal of the Chinese Medical Association : JCMA
IV. Prevalence Study

Of the 59 suspected cases, 41 patients were confirmed by nextgeneration sequencing or real-time reverse transcription-polymerase chain reaction (RT-PCR).
The spike protein may serve as a vaccine candidate, but the effect to human requires further evaluation.
2020 Wu et al Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP)
J Chin Med Assoc
IV. Prevalence Study

Of the 59 suspected cases, 41 patients were confirmed by nextgeneration sequencing or real-time reverse transcription-polymerase chain reaction (RT-PCR).
The spike protein may serve as a vaccine candidate, but the effect to human requires further evaluation.
2020 Du et al Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
Frontiers in Microbiology
III-3. Time Series Analysis Although a large number of SARS and MERS subunit vaccines have been developed with potent immunogenicity and/or protection in available animal models, virtually all remain in the preclinical stage.
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
The use of remdesivir may be a good candidate as an investigational treatment.

Based on the most recent MERS-CoV outbreak, there are already a number of vaccine candidates being developed but most are still in the preclinical testing stage.
2020 Al-Qaness et al Optimization Method for Forecasting Confirmed Cases of COVID-19 in China
J Clin Med
IV. Computer Model Apply the testing set to the best ANFIS model.
2020 Andersen et al Discovery and development of safe-in-man broad-spectrum antiviral agents
International Journal of Infectious Diseases
IV. Other On the other hand, these models allow researchers to predict the behavior of viruses in vivo and, therefore, to reduce animal use and in cases where animal models are unavailable to initiate clinical trials.
2020-01-28 Chan et al Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan
Emerg Microbes Infect
IV. Other Thus the broad spectrum antiviral peptides against S2 would be an important preventive and treatment modality for testing in animal models before clinical trials .
2020-02-18 Xiaoxuan et al Can Search Query Forecast successfully in China's 2019-nCov pneumonia?
medrxiv
IV. Computer Model From the above model fitting results, it can be seen that the prediction model based on filtering noise reduction has the best fitting effect among the three prediction model, followed by the prediction model based on search composite index.

This kind of study focuses on exploring effective epidemic predictive model for the purpose of early warning of epidemic.
2020-02-18 Zhou et al Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions
medrxiv
IV. Prevalence Study

The infection status of a total of 2,666 individuals that successfully evacuated from Wuhan between Jan. 29 and Feb. 2, 2020 were used in this study.
where M is the number of candidate models.

Both the SEIR and SEAIR models were fitted to the infection data, and SEIR model has better performance than the SEAIR model based on WAIC (Table 1) .
2020-02-25 Chong et al A Novel Method for the Estimation of a Dynamic Effective Reproduction Number (Dynamic-R) in the CoViD-19 Outbreak
medrxiv
IV. Other Third, the method is exceedingly complex, with constant debate on the best methods of curve fitting, and the best models to use to calculate the R value.
2020-02-28 Lillie et al Novel coronavirus disease (Covid-19): The first two patients in the UK with person to person transmission
Journal of Infection
IV. Other There was no clinical indication for the use of experimental antiviral therapies.
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
Development of animal models that faithfully mimic SARS-CoV-2 infection in humans is critical not only in providing a more refined understanding of the pathogenic mechanisms involved but also to serve as a screening model for potential chemotherapeutic agents and vaccines.
2020-03-03 Xu et al Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential
ACS Infect Dis
III-3. Time Series Analysis

The outbreak of SARS in southern China between November 2002 and July 2003 eventually resulted in 8098 confirmed cases and 774 deaths reported in 17 countries with a mortality rate of 9%, while MERS, first identified in Saudi Arabia in 2012, has caused a total of 2519 laboratory-confirmed cases including 866 associated deaths with a fatality rate of nearly 34% at the end of January 2020.
We envision that once its anti-SARS-CoV-2 activity is validated in animal models or human clinical trials, niclosamide and its optimized analogues may be developed as effective antiviral therapeutics with the potential to benefit numerous infected patients in this outbreak of COVID-19.
2020-03-04 Memish et al Middle East respiratory syndrome
The Lancet
II. Randomized Controlled Trial

A retrospective study of 136 patients with MERS found that macrolide therapy resulted in no reduction in mortality or faster MERS-CoV RNA clearance compared with those who were not treated with macrolides.
WHO target product profiles for MERS-CoV vaccines calls for the development of three types of MERS vaccines: a human vaccine for long-term protection of people at high exposure risk, such as health-care workers and those working with potentially infected camels; a human vaccine for reactive use in outbreak settings; and a dromedary camel vaccine to prevent zoonotic trans mission.
2020-03-04 Wu et al Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses
biorxiv
IV. Other For NJ analyses, JTT+G was selected as the best model.
2020-03-06 Kraemer et al The effect of human mobility and control measures on the COVID-19 epidemic in China
medrxiv
IV. Computer Model In 10 provinces, both testing and mobility improve the models prediction and in only one province testing is the most important factor improving model prediction (Fig.
2020-03-13 Singhal et al A Review of Coronavirus Disease-2019 (COVID-19)
Indian J Pediatr
IV. Prevalence Study

The median age was 8 y 11 mo and in 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China.
A candidate vaccine is under development.
2020-03-15 Yi et al COVID-19: what has been learned and to be learned about the novel coronavirus disease
Int J Biol Sci
IV. Prevalence Study

On February 11, 2020, a multi-center study on 8,866 patients including 4,021 confirmed COVID-19 patients presented a more updated illustration of the epidemic as follows ( UlBi-HX_rHPXa1qHA2bhdA).
Live-attenuated vaccines have been evaluated in animal models for SARS .
2020-03-16 Grifoni et al A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2
Cell Host & Microbe
IV. Other This analysis provides essential information for understanding human immune responses to this virus and for evaluating diagnostic and vaccine candidates.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other 56 Genetic engineering was used in the generation of 288-330 +/+ MERS-CoV mouse model, which is being used for the evaluation of novel MERS-CoV vaccines and drugs.

51 The first animal model used for developing a MERS-CoV vaccine was rhesus macaques.

43 47 These hamsters are a potential model for studying CoV pathology and pathogenesis and vaccine efficacy.
2020-03-18 Dehesh et al Forecasting of COVID-19 Confirmed Cases in Different Countries with ARIMA Models
medrxiv
IV. Computer Model The model which has the least AIC was selected as the best model.

The aim of this study is first to find the best predicting models for confirmed cases in countries with high number of confirmed cases in the world and second to predict confirmed cases with these models.
2020-03-18 Duan et al Advance of promising targets and agents against 2019-nCoV in China
Drug Discovery Today
IV. Other Drawing experience from effective screening strategies on antitumor drug development, the credible and large-scale screening system of the especially deadly coronaviruses must be set up at the molecular level and in animal models as soon as possible.
2020-03-20 Jeon et al Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
biorxiv
IV. Other These drugs will be tested in an appropriate animal model for their antiviral activities.
2020-03-20 Belhadi et al A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19
medrxiv
II. Randomized Controlled Trial

Phase IV trials were the most commonly reported study type (n=27, 23%).
30 In mouse infection models, remdesivir had therapeutic efficacy against SARS-CoV and MERS-CoV.
2020-03-23 Rios et al Effectiveness and safety of antiviral or antibody treatments for coronavirus
medrxiv
III-2. Matched Case Control

The four cases reports/series 29,45,46,48 that included immunosuppressed patients with MERS (5 patients) and unspecified coronavirus (2 patients) reported 3 deaths all in patients with hematological malignancies treated with foscarnet (n=1) and oseltamivir (n=2).
No animal or human trials investigating monoclonal antibodies for the treatment of COVID-19 were found in this rapid review.
2020-03-23 Zhang et al COVID-19: Melatonin as a potential adjuvant treatment
Life Sciences
II. Randomized Controlled Trial

A recent meta-analysis of a total of 22 randomized controlled trials suggested that a supplementary use of melatonin is associated with a significant reduction of TNF-α and IL-6 level .
Although the direct evidence of melatonin application in COVID-19 is unclear, both its use in experimental animal models and in studies on humans have continuously documented its efficacy and safety and its use by COVID-19 patients predictably would be highly beneficial.
2020-03-23 Koczkodaj et al 1,000,000 cases of COVID-19 outside of China: The date predicted by a simple heuristic
Global Epidemiology
IV. Computer Model The extrapolation is a mathematical estimation, predicting unknown future values based on existing values.
2020-03-23 Luo et al Prognostic value of C-reactive protein in patients with COVID-19
medrxiv
IV. Prevalence Study

Hence, 298 patients were finally enrolled in this study, including 141 cases of ordinary illness and 157 cases of severe or critical illness on admission.
With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%.
2020-03-25 Chua et al The role of CT in case ascertainment and management of COVID-19 pneumonia in the UK: insights from high-incidence regions
The Lancet Respiratory Medicine
IV. Prevalence Study

A similar CT sensitivity of 98% (vs 71% for rtRT-PCR; p<0·001) was found in a smaller study of 51 patients, in which just under a third (15 [29%] patients) tested negative on the initial rtRT-PCR.
In a cohort of just over 1000 cases, 3 CT was reported to have a diagnostic sensitivity of 97%, positive predictive value of 65%, and negative predictive value of 83%.
2020-03-25 Qiang et al Using the spike protein feature to predict infection risk and monitor the evolutionary dynamic of coronavirus
Infect Dis Poverty
IV. Prevalence Study

The features of the 507 human samples in our dataset were used to show the patterns with the multidimensional scaling method.
The 10-fold cross validation method was used to evaluate the predictive performance.
2020-03-26 Zhang et al Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis
Respir Res
IV. Other Secondly we applied different evaluation index: when assessing the relationship between candidates with the severity of 2019 novel coronavirus pneumonia, we used the highest or lowest level of candidates during hospitalization while the previous studies mainly used the fixed value of candidates on admission.
2020-03-27 Moghadami et al Modeling the Corona Virus Outbreak in IRAN
medrxiv
IV. Computer Model The predictive model will be tested against four regression model evaluations for robustness.
2020-03-27 Zhou et al A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China
medrxiv
III-2. Cross Sectional Control

Between January 1 and February 28, 2020, a total of 393 patients with COVID-19 were enrolled, but only 377 eligible participants were finally included in our analysis.
The negative predictive value of less than 5.32 for the N/LCRPD-dimer was 93.75%, while the positive predictive value was 46.03% in the test sets.

In general, the product of N/LCRPD-dimer is a new predictive value for the severity of COVID-19.

The predictive value of N/LCRPD-dimer was also confirmed in the internal validation stage.
2020-03-27 Ficetola et al Climate affects global patterns of COVID-19 early outbreak dynamics
medrxiv
III-3. Time Series Analysis

We define a local outbreak event when at least 50 positive cases were detected in a given country/region, and calculated the growth rate of confirmed Covid-19 cases between day 1 and day 5, when day 1 was the day at which the 50 cases 10 threshold was reached.
AIC trades-off explanatory power vs. number of predictors; parsimonious models explaining more variation have the lowest AIC values and are considered to be the "best models" .
2020-03-27 Wynants et al Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection
medrxiv
I. Systematic Review

Based on nine of the 15 studies that reported study dates, data were collected between 8 th December 2019 and 3 rd March 2020.
Diagnostic and prognostic models for COVID-19 are available and they all appear to show good to excellent discriminative performance.
2020-03-27 Shang et al CHEER: hierarCHical taxonomic classification for viral mEtagEnomic data via deep leaRning
biorxiv
IV. Prevalence Study When we use the best hit as the prediction the accuracy is only 64%.
2020-03-30 Liu et al Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2
medrxiv
IV. Other Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively.
2020-03-30 Jagadesh et al In search for the hotspots of Disease X: A biogeographic approach to mapping the predictive risk of WHO s Blueprint Priority Diseases
medrxiv
IV. Other Models were evaluated and a weighed mean was used to map the predictive risk of disease emergence.
2020-03-31 Chen et al Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2
biorxiv
IV. Prevalence Study The fact that SARS-CoV-2 replicates efficiently in the upper respiratory tract of ferrets makes them a candidate animal model for evaluating antiviral drugs or vaccine candidates against COVID-19.
2020-03-31 Lai et al Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
International Journal of Antimicrobial Agents
IV. Other The effective option of antiviral therapy and vaccination are currently under evaluation and development.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model Development of drugs is also hampered by various evaluation methods and animal models used for testing drug activity among different labs worldwide, which could postpone selection of the best drug for clinical trials.

5 Capabilities to discover a therapeutic (not vaccine) for the disease, and clinical effectiveness studies to discover therapeutics, to include antiviral agents.

5.0.0.1 Highlights

5.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Andersen et al Discovery and development of safe-in-man broad-spectrum antiviral agents
International Journal of Infectious Diseases
IV. Other Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases.
2020 Shanmugaraj et al Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19)
Asian Pacific Journal of Allergy and Immunology
IV. Other Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.
2020 Li et al Puzzle of highly pathogenic human coronaviruses (2019-nCoV)
Protein Cell
IV. Computer Model Thirty drug candidates, consisting of biologically active natural products and traditional Chinese medicine drugs, that have the potential to show therapeutic effects against 2019-nCoV, were chosen for testing for the clinical treatment of pneumonia in patients infected with 2019-nCoV.
2020 Wang et al Science in the fight against the novel coronavirus disease
Chin Med J (Engl)
II. Randomized Controlled Trial

They performed a metagenomic analysis of respiratory tract specimens obtained from five patients suffering from the pneumonia in question and identified the virus now known as 2019-nCoV as the causative agent.
As specific therapies targeting 2019-nCoV are lacking, it may be useful to repurpose drugs already licensed for marketing or clinical trials to treat COVID-19 patients in an emergency response; researchers are actively working to identify such drugs.
2020 Zhang et al In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus
Journal of Integrative Medicine
IV. Other While specific vaccines and antiviral agents are the most effective methods to prevent and treat viral infection, there are not yet effective treatments that target the 2019-nCoV.
2020-01-28 Xu et al Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation
biorxiv
IV. Other Studies for identifying the inhibitors of 2019-nCov M pro were quickly performed for discovering and developing drugs against the disease.
2020-02-11 Sarkar et al The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19
biorxiv
IV. Other Therefore, our present study should help the scientists to develop potential vaccines and therapeutics against the Wuhan Novel Coronavirus 2019.
2020-02-14 Wang et al What to do next to control the 2019-nCoV epidemic?
The Lancet
IV. Other 13 Many efforts, including several clinical trials, such as NCT04246242 and NCT04252664, are in progress to screen existing antiviral drugs to identify those that could be specific and efficient against 2019-nCoV.
2020-02-26 Rothan et al The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak
Journal of Autoimmunity
IV. Other Thus, these therapeutic agents can be considered to treat COVID-19 infection .

At present, there are no specific antiviral drugs or vaccine against COVID-19 infection for potential therapy of humans.
2020-02-26 Liao et al The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing
medrxiv
IV. Prevalence Study

At the individual levels, we also found the higher T cell clonality was consistently remained in the 3 mild patients as compared to the 3 severe patients ( Figure 4D ), supporting that highly expanded CD8 + T cell participated in resolving the SARS-CoV-2 infection.
Although researchers are racing against time to develop vaccines and test anti-viral drugs in clinical trials , there is no effective prophylactic and clinical treatment for COVID-19 yet.
2020-02-27 Jin et al Structure of Mpro from COVID-19 virus and discovery of its inhibitors
biorxiv
IV. Other Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.
2020-03-02 Ko et al Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
biorxiv
IV. Other Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
2020-03-02 Zhu et al The novel coronavirus outbreak in Wuhan, China
Glob Health Res Policy
IV. Prevalence Study Scientists all over the world need to understand COVID-19 and discover potentially effective antiviral treatments and vaccines; epidemiologists need to conduct intensive contact investigations; It is important to promote protection knowledge for the general public .
2020-03-03 Xu et al Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential
ACS Infect Dis
III-3. Time Series Analysis

The outbreak of SARS in southern China between November 2002 and July 2003 eventually resulted in 8098 confirmed cases and 774 deaths reported in 17 countries with a mortality rate of 9%, while MERS, first identified in Saudi Arabia in 2012, has caused a total of 2519 laboratory-confirmed cases including 866 associated deaths with a fatality rate of nearly 34% at the end of January 2020.
67 These findings, together with its broad antiviral properties, indicate that niclosamide, an inexpensive and well-tolerated old drug, may be repurposed with therapeutic potential applications to combat COVID-19.
2020-03-04 Memish et al Middle East respiratory syndrome
The Lancet
II. Randomized Controlled Trial

A retrospective study of 136 patients with MERS found that macrolide therapy resulted in no reduction in mortality or faster MERS-CoV RNA clearance compared with those who were not treated with macrolides.
68 Co-infection of MERS-CoV with other respiratory viruses (such as parainfluenza The pathogen: MERS-CoV Anti-viral therapeutics including host-directed therapies or immune-based therapies are in development.
2020-03-07 Zhao et al Appealing for Efficient, Well Organized Clinical Trials on COVID-19
medrxiv
IV. Other These trials are classified into 4 categories based on treatment modalities, including chemical drugs, biological therapies, traditional Chinese medicine treatments and other therapies.
2020-03-08 Rut et al Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design
biorxiv
IV. Other Currently, there is no effective antiviral treatment for COVID-19, therefore research efforts are focused on the rapid development of vaccines and antiviral drugs.

The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.
2020-03-12 Xiong et al Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2
biorxiv
IV. Other However, although great efforts have been made by the research community to discover therapeutic antiviral agents for coping with such emergencies, specific and effective drugs or vaccines with low toxicity have been rarely reported 2 .
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other Scientists and physicians worldwide have been conducting a major campaign to understand this new emergent disease and its epidemiology in an effort to uncover possible treatment regimens, discover effective therapeutic agents, and develop vaccines.

55 Additional collaboration in the areas of antiviral discovery processes and clinical trial performance will enhance patients' access to drug candidates with improved therapeutic potential and ideally reduce the amount of time required to bring these drugs to market.

More than 500 patents that disclose the use of four biologics classes such as therapeutic antibodies, cytokines, RNA therapies, and vaccines to treat and prevent SARS and MERS have been analyzed for this study.

Thus, for both diseases, more patents have been devoted to the development of therapeutic agents as opposed to diagnostic methods and vaccines.
2020-03-12 Yao et al A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus–A Possible Reference for Coronavirus Disease-19 Treatment Option
Journal of Medical Virology
I. Systematic Review There are no specific antiviral therapies for COVID-19.
2020-03-12 Ge et al A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
biorxiv
IV. Other Considering that the development of a new drug generally takes years, probably the best therapeutic shortcut is to apply the drug repositioning strategy (i.e., finding the new uses of old drugs) to identify the potential antiviral effects against SARS-CoV-2 of existing drugs that have been approved for clinical use or to enter clinical trials.
2020-03-13 Baron et al Teicoplanin: an alternative drug for the treatment of COVID-19?
International Journal of Antimicrobial Agents
IV. Other Drug repurposing is an effective way to quickly identify therapeutic drugs with a known safety profile to treat an emerging disease.
2020-03-16 Mehta et al COVID-19: consider cytokine storm syndromes and immunosuppression
The Lancet
IV. Other Current focus has been on the development of novel therapeutics, including antivirals and vaccines.
2020-03-16 Hemida et al The SARS-CoV-2 outbreak from a one health perspective
One Health
IV. Prevalence Study This sequence will have a significant impact on the development of novel diagnostic assays, antiviral drugs, and vaccines against the virus soon.
2020-03-17 Ortega et al Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target
EXCLI J
IV. Other The ongoing efforts toward discovering efficient drugs to prevent and treat SARS-CoV-2 infection should include the prior structural and pharmacological knowledge gained with the other coronavirus outbreaks.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other 65 These antibodies could be useful tools also in the development of vaccines, therapeutic drugs, and antiviral inhibitors.

Achievements in the development of vaccines and therapeutic agents for SARS-and MERS-CoV as well as recent ongoing progress for COVID-19 will facilitate the development of effective vaccines and therapeutics against this emerging virus.

3, 5, These valuable options can be exploited for their potency, efficacy, and safety along with expediting other ongoing research 2, 4, so as to discover valuable modalities for tackling the emerging COVID-19, but as yet there is no effective vaccine or therapeutic, for which intense efforts are ongoing.

There are no effective vaccines or specific antiviral drugs for COVID-19.

Hence, current efforts should be directed toward identifying and evaluating drugs and immunotherapeutics that have proven efficacy against viruses similar to COVID-19.
2020-03-18 Cai et al Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study
Engineering
III-1. Pseudo-Randomized Controlled Trial

For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms.
One efficient approach to discover effective drugs is to test whether the existing antiviral drugs are effective in treating other related viral infections.

Therefore, clinical studies are urgently needed to evaluate the efficacy and safety of this antiviral nucleoside for COVID-19 treatment.
2020-03-20 Belhadi et al A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19
medrxiv
II. Randomized Controlled Trial

Phase IV trials were the most commonly reported study type (n=27, 23%).
2 To encourage the development of clinical trials that test therapeutics against SARS-CoV-2, the WHO has suggested a number of candidate antiviral agents that have to be tested in clinical trials.

Our search strategy was designed to identify all the clinical trials using antiviral agents that were registered for COVID-19.
2020-03-20 Jeon et al Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
biorxiv
IV. Other In this study, we screened a panel of FDA-approved drugs to identify antiviral drug candidates for the treatment of COVID-19 and suggest the identified drug candidates may be considered for therapeutic development.
2020-03-25 Li et al FEP-based screening prompts drug repositioning against COVID-19
biorxiv
IV. Other There are no specific drugs or vaccines against COVID-19, thus effective antiviral agents are still urgently needed to combat this virus.
2020-03-28 Zhai et al The epidemiology, diagnosis and treatment of COVID-19
International Journal of Antimicrobial Agents
III-2. Matched Case Control

Another study later using the travel history and symptom onset of 88 confirmed cases had a similar mean incubation period, which was 6.4 days (95% CI: 5.6-7.7) .
The efficacy and safety of these antiviral agents for COVID-19 will be assessed by further clinical trials.

Current clinical trials are under investigation to demonstrate the efficacy of new antiviral drugs, convalescent plasma transfusion, and vaccines.
2020-03-29 Li et al Coronavirus disease 2019 (COVID-19): current status and future perspective
International Journal of Antimicrobial Agents
III-2. Retrospective Cohort

Analysis of the first 99 confirmed cases of SARS-CoV2 infection revealed that cytokine storm syndromes occurred in patients with severe COVID-19 and 17 (17%) had ARDS and, among them, 11 (11%) patients deteriorated within a short period of time and died of multiple organ failure .
4) Further evaluation of the efficacy of current antiviral drugs in clinical applications is needed.
2020-03-29 Kang et al Recent Progress in understanding 2019 Novel Coronavirus associated with Human Respiratory Disease: Detection, Mechanism and Treatment
International Journal of Antimicrobial Agents
IV. Prevalence Study In addition, combination therapies of interferon with other antiviral drugs have been used to treat SARS or MERS patients and show synergistic effects 60, 74 .
2020-03-30 Zhou et al Clinical features and outcomes of 197 adult discharged patients with COIVD-19 in Yichang, Hubei
medrxiv
IV. Prevalence Study

For the coagulation tests, Prothrombin time (PT) and activated partial thromboplastin time (APTT) were at the normal range in the majority of patients, while fib was above the normal range in the 78 (39.6%) patients, D-dimmer was above the normal range in the 99 (47.2%) patients.
At present, there was no vaccine and antiviral drugs against this disease.
2020-03-30 Fan et al Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study
medrxiv
IV. Other No effective antiviral drugs that treat COVID-19 have been identified to date, and opinions on whether antiviral drugs should even be used to treat COVID-19 differ.
2020-03-31 Li et al The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future
Microbes and Infection
IV. Prevalence Study

11 January 2020 41 patients have been diagnosed to have infection of the novel coronavirus, with 763 close contacts, 7 severe cases and the first death.
Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures.
2020-03-31 Wang et al COVID-19 in Hemodialysis Patients: A Report of 5 Cases
American Journal of Kidney Diseases
IV. Other There are no antiviral drugs of proven efficacy or applicable vaccines.
2020-07-31 Shereen et al COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses
Journal of Advanced Research
IV. Prevalence Study

In 2001 the samples were isolated from the healthy persons of Hongkong and the molecular assessment showed 2.5% frequency rate of antibodies against SARS-coronavirus.
However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery.

6 Alternative models to aid decision makers in determining how to prioritize and distribute scarce, newly proven therapeutics as production ramps up. This could include identifying approaches for expanding production capacity to ensure equitable and timely distribution to populations in need.

6.0.0.1 Highlights

6.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Shanmugaraj et al Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development
Pathogens
IV. Prevalence Study The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection.
2020 Minjin Wang et al A precision medicine approach to managing Wuhan Coronavirus pneumonia
Precision Clinical Medicine
IV. Prevalence Study

As of January 29, 2020, the virus had been diagnosed in more than 7,000 patients in China and 77 outside this country.
10 A precision medicine approach is crucial to quickly confirm the diagnosis with laboratory methods, control the spread of the virus, and better allocate hospital resources.
2020-02-02 Kucharski et al Early dynamics of transmission and control of COVID-19: a mathematical modelling study
medrxiv
IV. Prevalence Study Such analysis can inform predictions about potential future growth , help estimate risk to other countries , and guide the design of alternative interventions .
2020-02-04 Zhang et al Recent advances in the detection of respiratory virus infection in humans
Journal of Medical Virology
IV. Other It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.
2020-02-09 Cao et al Incorporating Human Movement Data to Improve Epidemiological Estimates for 2019-nCoV
medrxiv
IV. Prevalence Study This will allow developing early detection, isolation and quarantine strategies tailored to the very dynamic epidemiological situation, as well as identify potential problems in the implementation of local disease control policies and inform the design of any necessary adjustments.
2020-02-11 Zhu et al Spatially Explicit Modeling of 2019-nCoV Epidemic Trend based on Mobile Phone Data in Mainland China
medrxiv
IV. Computer Model Our predictions of three future scenarios, namely the current trend maintained, control efforts expanded, person-to-person contacts increased due to work resuming, provide information for decision makers to allocate resources for controlling the disease spread.
2020-02-18 Fu et al Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses
medrxiv
IV. Computer Model The estimated potential total number of confirmed cases and key dates for the SARS-CoV-2 outbreak may provide certain guidance for governments, organizations and citizens to optimize preparedness and response efforts.
2020-02-19 Zhang et al A Novel Coronavirus (COVID-19) Outbreak A Call for Action
Chest
IV. Prevalence Study

12 In the last 2 weeks of January 2020, thirteen children were diagnosed, fortunately with a mild clinical presentation.
The information produced by this research allows the medical and scientific communities to better understand the transmission of COVID-19, to develop rapid diagnostic tests and efficient epidemiologic control, and to facilitate the development of antiviral therapies and vaccines.
2020-02-20 Ling et al COVID-19: A critical care perspective informed by lessons learnt from other viral epidemics
Anaesthesia Critical Care & Pain Medicine
IV. Other ICU management teams have the responsibility to make these needs known to relevant authorities to ensure proper forward planning and adequate procurement.
2020-02-21 Heymann et al Data sharing and outbreaks: best practice exemplified
The Lancet
IV. Other Such rapidly shared scientific information can be used to provide real-time guidance for epidemiologists working to contain the outbreak, clinicians managing patients, and modellers helping to understand potential future directions and the possible effectiveness of various interventions.
2020-02-25 Song et al Deep learning Enables Accurate Diagnosis of Novel Coronavirus (COVID-19) with CT images
medrxiv
IV. Other Conclusions The established models can achieve a rapid and accurate identification of COVID-19 in human samples, thereby allowing identification of patients.
2020-03-02 Zhu et al The novel coronavirus outbreak in Wuhan, China
Glob Health Res Policy
IV. Prevalence Study Scientists all over the world need to understand COVID-19 and discover potentially effective antiviral treatments and vaccines; epidemiologists need to conduct intensive contact investigations; It is important to promote protection knowledge for the general public .
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
The use of detection kits can accelerate accurate diagnosis of patients, help to determine quarantine and isolation requirements, assist in determining the treatment of patients and save limited medical resources.
2020-03-06 Riou et al Adjusted age-specific case fatality ratio during the COVID-19 epidemic in Hubei, China, January and February 2020
medrxiv
IV. Prevalence Study

The model estimates that a total of 82,300 individuals (95%CrI: 73,000-91,800) were infected in Hubei between 1 January and 11 February 2020.
Clinicians need to know age-and sex-specific mortality among symptomatic patients seeking care to assess prognosis and, in severe situations, prioritize patients with the best expected outcomes.
2020-03-08 Rao et al Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis
medrxiv
IV. Prevalence Study

recently carried out a nationwide analysis of 1,590 patients with laboratory-confirmed COVID-19 and suggested that cancer patients might have a higher infection risk than those without 39 .
This analysis may help to prioritize resources for better prevention of the infection in those susceptible subjects.
2020-03-11 Kucharski et al Early dynamics of transmission and control of COVID-19: a mathematical modelling study
The Lancet Infectious Diseases
IV. Prevalence Study 4, 5 Such analysis can inform predictions about potential future growth, 6 help estimate risk to other countries, 7 and guide the design of alternative interventions.
2020-03-13 Verity et al Estimates of the severity of COVID-19 disease
medrxiv
IV. Prevalence Study

We used data from 169 recovered individuals with reported recovery dates and reported/imputed onset dates to estimate the onset to recovery distribution.
Assessing the severity of COVID-19 is critical to determine both the appropriateness of mitigation strategies and to enable planning for healthcare needs as epidemics unfold.
2020-03-14 Wang et al SARS-CoV-2 invades host cells via a novel route: CD147-spike protein
biorxiv
IV. Other Therefore, intensive researches are urgently needed to elucidate the invasive mechanisms of SARS-CoV-2, thereby providing a potential target for developing specific antiviral drugs.
2020-03-16 Jain et al Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection
medrxiv
I. Systematic Review

Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion.
To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID−19.

As the number of hospitalised COVID-19 cases continues to increase, hospitals will increasingly need to ration limited resources and improve clinical pathways to effectively prioritise patients with greatest clinical need.
2020-03-18 Fenga et al CoViD--19: An Automatic, Semiparametric Estimation Method for the Population Infected in Italy
medrxiv
III-3. Time Series Analysis

Obtained results show that, while official data at March the 12th report 12.839 cases in Italy, people infected wiyh the SARSCoV2 could be as high as 105.789.
4. from a uniform distribution in , generate T pseudorandom numbers and define the interval R t = (t/T ; t + 1/T ] for t = 0, 1, .
2020-03-19 Zhao et al A systematic approach is needed to contain COVID-19 globally
Science Bulletin
IV. Prevalence Study Secondly, governments of countries need to strive for a unified and equitable allocation of resources and to improve the efficiency of resource distribution through coordinated management.
2020-03-20 Nkengasong et al Looming threat of COVID-19 infection in Africa: act collectively, and fast
The Lancet
IV. Prevalence Study The study provides a valuable tool that can help countries in Africa prioritise and allocate resources as they prepare to respond to the potential introduction and spread of COVID-19.

Models that enable the continent to better allocate scarce resources to better prepare and respond to the COVID-19 epidemic are crucial.
2020-03-20 Zhou et al COVID-19: Challenges to GIS with Big Data
Geography and Sustainability
IV. Computer Model In this case, the key to epidemic prevention and control is knowing the spatiotemporal dynamics of the supply and demand for medical resources to optimize the allocation of materials.
2020-03-20 Zhu et al Reverse transcription loop-mediated isothermal amplification combined with nanoparticles-based biosensor for diagnosis of COVID-19
medrxiv
IV. Other Rapid and precise diagnostic methods are thus immediately needed for diagnosing COVID-19, providing timely treatment and facilitating infection control.
2020-03-20 Rossman et al A framework for identifying regional outbreak and spread of COVID-19 from one-minute population-wide surveys
medrxiv
IV. Prevalence Study

To this date, March 21st, 18pm, there have been 54,059 responses, including 50,572 (93.55%) adults and 3,488 (6.45%) children.
Such information can provide a valuable tool for decision makers to decide which areas need strengthening of social distancing measures and which areas can be relieved.
2020-03-20 Ahmadi et al Modeling and Forecasting Trend of COVID-19 Epidemic in Iran
medrxiv
IV. Computer Model their relationship to outcomes should be analyzed to evaluate the cost-effectiveness of various diagnostic therapeutic approaches.
2020-03-20 Guan et al Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT
Academic Radiology
IV. Prevalence Study

Among the three patients, the CT images still showed normal lungs in one patient, and GGO in the lower lobes in the other two patients (Fig 5) .
Identification of CT features of COVID-19 pneumonia provide timely diagnostic evidence of the disease enabling early diagnosis and treatment.
2020-03-23 Wang et al Effectiveness and cost-effectiveness of public health measures to control COVID-19: a modelling study
medrxiv
IV. Prevalence Study The purpose of this study was to assess the effectiveness and cost-effectiveness of different public health measures and provide the suggestions and assist decision and policy makers in making better decisions and resources allocations in the fight with COVID-19 outbreak.
2020-03-23 Coelho et al Assessing the potential impacts of COVID-19 in Brasil: Mobility, Morbidity and Impact to the Health System
medrxiv
IV. Prevalence Study The resulting maps should help authorities in their efforts to prioritize actions and if resource allocation to mitigate the effects of the pandemic.
2020-03-23 Stedman et al COVID-19: Modelling Local Transmission and Morbidity effects to provide an estimate of overall Relative Healthcare Resource Impact by General Practice Granularity
medrxiv
IV. Prevalence Study This model provides a method for predicting relative local levels of disease burden based on defined criteria and thereby providing a method for targeting limited (and perhaps soon to be scarce) care resources to optimise national, regional and local responses to the COVID-19 outbreak.
2020-03-27 Kim et al Modelling SARS-CoV-2 Dynamics: Implications for Therapy
medrxiv
IV. Computer Model Identification of SARS-CoV-2-specific virus 216 characteristics is needed to design optimal treatments and to ensure that limited 217 resources are deployed effectively.
2020-03-30 Ansari et al Deliberate release: Plague – A review
Journal of Biosafety and Biosecurity
IV. Other The next steps would be to create a viable vaccine, continue research on novel therapies, distribute rapid diagnostic tests, and raise the awareness of clinicians to the possibility of an attack.
2020-03-30 Huang et al Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis
medrxiv
IV. Prevalence Study

In this study, we retrospectively analyzed the clinical characteristics of 97 those patients who progressed to severe pneumonia later and found that five CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Therefore, the most crucial issue is 80 to identify these patients and prioritize their treatment strategy by applying 81 .
2020-03-30 Murray et al Forecasting COVID-19 impact on hospital bed-days, ICU-days, ventilator-days and deaths by US state in the next 4 months
medrxiv
IV. Computer Model These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity.
2020-03-30 Beltran-Pavez et al SARS-CoV-2 detection from nasopharyngeal swab samples without RNA extraction
biorxiv
IV. Other Since the current demand for those kits largely exceeds their offer, it is necessary to develop alternative strategies allowing a rapid detection of the virus.
2020-03-30 Lin et al Which Measures are Effective in Containing COVID-19? Empirical Research Based on Prevention and Control Cases in China
medrxiv
IV. Prevalence Study These models enable epidemiologists and health authorities to understand the transmission process, predict its impact on healthy populations, and assess the effectiveness of different mitigation and prevention strategies.
2020-03-30 Xie et al Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19
medrxiv
III-2. Retrospective Cohort

Second cohort of 151 patients admitted to Jinyintan hospital who were included in a previous study were reused for model validation.
Since early identification and effective treatment can reduce mortality and morbidity as well as relieve resource shortages, there is an urgent need for effective prediction models to identify patients who are most likely to develop respiratory failure and poor outcomes.
2020-03-31 Calton et al Telemedicine in the Time of Coronavirus
Journal of Pain and Symptom Management
IV. Other First, we must find creative ways to ensure that all patients have equitable access to this valuable resource.

Next steps include ensuring equitable access to affordable telemedicine technology for vulnerable populations through creative solutions and financing, and dedicated attention to telemedicine evaluation and quality improvement.
2020-03-31 Lai et al Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
International Journal of Antimicrobial Agents
IV. Other All effort s are being made to slow the spread of the illness in order to provide time to better prepare healthcare systems and the general public, to better characterise COVID-19 to guide public-health recommendations, and to develop timely diagnostics, therapeutics and vaccines .
2020-03-31 Adams et al Goals of Care in a Pandemic: Our Experience and Recommendations
Journal of Pain and Symptom Management
IV. Other Innovative strategies and tools must be developed to minimize disease exposure and reach as many patients as possible before they develop critical illness.
2020-03-31 FINEGAN et al International Committee of the Red Cross (ICRC): General Guidance for the Management of the Dead Related to COVID-19
Forensic Science International: Synergy
IV. Other The measures required for effectively assisting in the management of the large numbers of dead from COVID-19 may likely need an increase of the human and material resources available, including for building local capacity and supporting and/or carrying out the recovery and identification processes.
2020-04-01 Xie et al Insight into 2019 novel coronavirus — an updated intrim review and lessons from SARS-CoV and MERS-CoV
International Journal of Infectious Diseases
IV. Prevalence Study Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions.
2020-04-01 Esposito et al Why is chest CT important for early diagnosis of COVID-19? Prevalence matters
medrxiv
IV. Prevalence Study

23 provide a reliable estimation of CT specificity, since it is the only study assessing performance in distinguishing COVID-19 (219 patients) from other ascertained viral interstitial pneumonia (205 patients).
Thus, the ability to obtain an expedite and reliable diagnosis in patients with a clinical suspicion of COVID-19 is imperative, to swiftly identify patients to be directed towards appropriate quarantine or care measures.
2020-04-01 Sultan et al AGA Institute Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic
Gastroenterology
I. Systematic Review

58, 59 First, the systematic reviews by Offeddu et al included a meta-analysis of 3 observational studies that showed a benefit in using N95 respirators over standard masks in protecting health care workers from SARS (OR = 0.86; 95% CI: 0.
Performance measures should assess whether decision making is appropriate.
2020-04-01 Pourhomayoun et al Predicting Mortality Risk in Patients with COVID-19 Using Artificial Intelligence to Help Medical Decision-Making
medrxiv
IV. Prevalence Study

In this study, we used documented data of 117,000 patients world-wide with laboratory-confirmed COVID-19.
The purpose of this study is to create a predictive algorithm to help hospitals and medical facilities maximize the number of survivors by providing an accurate and reliable tool to help medical decision making and triage COVID-19 patients more effectively and accurately during the pandemic.
2020-04-01 Shayak et al Transmission Dynamics of COVID-19 and Impact on Public Health Policy
medrxiv
IV. Computer Model Extensive planning to allocate the resources for management of cases, measures like quarantine and social distancing and simultaneously building capacity for innovative approaches to arrange for testing kits should be executed in the initial stages of the epidemic.
2020-05-31 Liu et al CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity
European Journal of Radiology
IV. Prevalence Study

Methods The CT manifestations and clinical data of 73 patients with COVID-19 were retrospectively collected in 6 hospitals from Jan 21 to Feb 3, 2020.
CT imaging can demonstrate typical features making the diagnosis of COVID-19 quite likely, which can help to rapidly screen patients, and to stratify the patients' severity to quickly develop effective treatment strategies.

7 Efforts targeted at a universal coronavirus vaccine.

7.0.0.1 Highlights

7.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
The vaccines in development include viral vector-based vaccine, DNA vaccine, subunit vaccine, virus-like particles (VLPs)-based vaccine, inactivated whole-virus (IWV) vaccine and live attenuated vaccine.

The vaccine candidates will be developed by the DNA, recombinant and mRNA vaccine platforms from these organizations .

The US CDC shared the protocol on the real time RT-PCR assay for the detection of the 2019-nCoV with the primers and probes designed for the universal detection of SARS-like coronavirus and the specific detection of 2019-nCoV.
2020 Ralph et al 2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness
Journal of Infection in Developing Countries
IV. Prevalence Study

On 8 January 2020, it was reported that a novel coronavirus had been sequenced from one patient and subsequently identified in some of the other patients with pneumonia , later reported as 15 of the 59 patients .
Several vaccine platforms exist with the ability to induce protective responses: killed whole virus vaccines; split-virion vaccines; subunit vaccines; live-attenuated viral vaccines; viruslike particle vaccines; nanoparticle vaccines; and nucleic acid vaccines (DNA and RNA).

In regard to choosing a vaccine target and platform, the vaccine candidate must be immunogenic and immune targeting must lead to virus neutralization or potent cytotoxic responses.

As vaccine candidates are identified, the requirement of animal models for vaccine development and evaluation will be essential.

The envelope protein (E) is also an attractive vaccine target that has been proposed for leverage in the development of live-attenuated vaccines .
2020 Amodio et al Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions
Healthcare (Basel)
IV. Prevalence Study Various vaccine strategies against coronavirus, such as using inactivated viruses, live-attenuated viruses, viral vectorbased vaccines, subunit vaccines, and recombinant proteins are under evaluation.
2020 Shanmugaraj et al Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development
Pathogens
IV. Prevalence Study This protein could be used as a potential vaccine candidate as it is the major target for neutralizing antibodies .
2020 Wang et al Science in the fight against the novel coronavirus disease
Chin Med J (Engl)
II. Randomized Controlled Trial

They performed a metagenomic analysis of respiratory tract specimens obtained from five patients suffering from the pneumonia in question and identified the virus now known as 2019-nCoV as the causative agent.
The development of neutralizing antibodies is underway, and efforts are also being made to develop a vaccine.
2020 Shang et al The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines
WHO
IV. Other This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.
2020-01-30 Ramaiah et al Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development
biorxiv
IV. Prevalence Study These immunodominant epitopes can be incorporated in universal subunit CoV vaccine.
2020-02-04 Ahmed et al Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies
biorxiv
IV. Other Overall, as the identified set of epitopes map identically to SARS-CoV-2, they present potentially useful candidates for guiding experimental efforts towards developing universal vaccines against SARS-CoV-2.
2020-02-05 McCloskey et al SARS to novel coronavirus – old lessons and new lessons
Epidemiology and Infection
IV. Prevalence Study Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine development and a candidate vaccine was ready for initial laboratory testing.
2020-02-08 Malik et al Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments
Vet Q
IV. Prevalence Study Other effective measures include One health approach, implementation of effective prevention and control strategies, rapid communication and networking, and exploring advances in science and technology for developing rapid and confirmatory diagnostics, enhancing disease surveillance and monitoring, implementation of strict biosecurity measures, and timely efforts toward designing appropriate and effective vaccines and therapeutics (Cheng et al.

Among them, the S protein-based vaccines include full-length S protein vaccines, viral vector-based vaccine, DNA-based vaccine, recombinant S proteinbased and recombinant RBD protein-based vaccines.
2020-02-11 Sarkar et al The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19
biorxiv
IV. Other This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics.

Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2.
2020-02-11 Abdelmageed et al Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach
biorxiv
IV. Other Accordingly, these epitopes were strongly recommended as promising epitopes vaccine candidate against T cell.
2020-02-21 alam et al Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019
biorxiv
IV. Other Protein E was used as target for SARS antivirals 6 , and studies using SARS-CoV with lacking or mutated protein E as vaccine candidates showed promising results .
2020-02-24 El Zowalaty et al From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach
One Health
IV. Prevalence Study

However, it was recently reported that the Chinese Centers for Disease Control and Prevention isolated SARS-CoV-2 from 33 samples out of 585 environmental samples collected from Huanan Seafood Market .
In addition, there is yet no universal influenza vaccine available against all influenza virus subtypes and hence seasonal influenza vaccines have to be updated annually and vaccines for pandemic preparedness are a challenge .

In addition, there is yet no universal influenza vaccine available against all influenza virus subtypes and hence seasonal influenza vaccines have to be updated annually and that vaccines for pandemic preparedness are a challenge .
2020-02-25 Han et al Coronavirus 2019-nCoV: A brief perspective from the front line
Journal of Infection
II. Randomized Controlled Trial

24 The most common symptoms are fever (87.9%), fatigue (69.6%), dry cough (67.7%) and myalgia (34.8%), and these are accompanied with rhinobyon, rhinorrhoea, pharyngalgia and diarrhea in few patients 24 ( Table 1 ) of these patients were characterized by dyspnea and hypoxemia, which can rapidly progress to acute respiratory distress syndrome (ARDS), septic shock, metabolic acidosis, coagulation dysfunction, and even multiple organ dysfunction syndrome (MODS) in one week.
At present, there is no vaccine or specific drugs for the human coronavirus.
2020-02-27 Li et al Epitope-based peptide vaccine design and target site characterization against novel coronavirus disease caused by SARS-CoV-2
biorxiv
IV. Other Great efforts are being made for the discovery of antiviral drugs, but there are no licensed therapeutic or vaccine for the treatment of SARS-CoV-2 infection available in the market.
2020-03-02 Qamar et al Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches
biorxiv
IV. Other This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2.
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
However, the difficulties and challenges of developing an effective vaccine have been discussed earlier, and the key to a successful vaccine program is to vaccinate people before an outbreak occurs, not begin to develop the vaccine during the outbreak.
2020-03-04 Memish et al Middle East respiratory syndrome
The Lancet
II. Randomized Controlled Trial

A retrospective study of 136 patients with MERS found that macrolide therapy resulted in no reduction in mortality or faster MERS-CoV RNA clearance compared with those who were not treated with macrolides.
121 Multiple types of vaccine candidates are in development including inactivated whole virus, live attenuated virus, viral vectored vaccines, subunit vaccines, and DNA vaccines.
2020-03-05 Li et al Molecular immune pathogenesis and diagnosis of COVID-19
Journal of Pharmaceutical Analysis
IV. Prevalence Study

Virus genome sequencing of five patients with pneumonia hospitalized from December 18 to December 29, 2019, revealed the presence of a previously unknown β-CoV strain in all of them .
There are several vaccination strategies against SARS-CoV, MERS-CoV tested in animals, including a live-attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and proteins vaccines .
2020-03-08 Tang et al AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2
biorxiv
IV. Other All the above available information paved a way to design new targeted covalent inhibitors (TCI) 7 against SARS-CoV-2.
2020-03-09 Anderson et al How will country-based mitigation measures influence the course of the COVID-19 epidemic?
The Lancet
IV. Other Vaccine development is underway, but the key issues are not if a vaccine can be developed but where phase 3 trials will be done and who will manufacture vaccine at scale.
2020-03-12 Wang et al A human monoclonal antibody blocking SARS-CoV-2 infection
biorxiv
IV. Other Vaccines and targeted therapeutics for treatment of this disease are currently lacking.
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other Their COVID-19 candidate vaccines targeting the S protein of SARS-CoV-2 were developed using their recombinant nanoparticle vaccine technology along with their proprietary adjuvant Matrix-M.
2020-03-13 Singhal et al A Review of Coronavirus Disease-2019 (COVID-19)
Indian J Pediatr
IV. Prevalence Study

The median age was 8 y 11 mo and in 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China.
A candidate vaccine is under development.
2020-03-15 Zheng et al SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat
Int J Biol Sci
IV. Other In addition, great effort should be made on the development of vaccine and antiviral drugs.
2020-03-16 Grifoni et al A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2
Cell Host & Microbe
IV. Other These predictions can facilitate effective vaccine design against this virus of high priority.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other There are no effective vaccines or specific antiviral drugs for COVID-19.

Researchers are searching for effective and suitable vaccine candidates and therapeutics for controlling the deadly COVID-19.

37 NIAID-VRC scientists are developing a vaccine candidate expressing SARS-CoV-2 S protein in the mRNA vaccine platform technology.
2020-03-18 Kandel et al Health security capacities in the context of COVID-19 outbreak: an analysis of International Health Regulations annual report data from 182 countries
The Lancet
IV. Prevalence Study 6 No specific antiviral therapies are available, and efforts to dev elop antivirals and a vaccine continue.
2020-03-19 Arshad Ali et al The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat
Journal of Infection and Public Health
III-3. Time Series Analysis

In 2002, a pandemic of SARS occurred endangering the lives of 8098 individuals with a mortality of 774 patients .
The nucleic acid vaccine approach is being utilized by the National Institute of Allergy and Infectious Diseases Vaccine Research Center.
2020-03-20 Zhang et al Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19)
medrxiv
IV. Other In contrast, the S protein is the common target when designing vaccines 7 based on neutralizing antibodies.
2020-03-21 Ong et al COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning
biorxiv
IV. Prevalence Study RV has been successfully applied to vaccine 92 discovery for pathogens such as Group B meningococcus and led to the license Bexsero 93 vaccine 12 .
2020-03-28 Miller et al Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study
medrxiv
IV. Other We also wondered if the middle high and high-income countries that have current universal vaccination policies (28 countries) would show a relationship between the number of cases and the year that the universal vaccination started.
2020-03-28 Watanabe et al Site-specific analysis of the SARS-CoV-2 glycan shield
biorxiv
IV. Prevalence Study It is apparent that the viral spike will be targeted by the full assortment of vaccine strategies from nucleic-acid based approaches 10 , whereby the viral protein is expressed in vivo, to recombinant strategies whereby viral glycoproteins are delivered with appropriate adjuvants.
2020-03-31 Tagliamonte et al Re-insights into origin and adaptation of SARS-CoV-2
biorxiv
IV. Prevalence Study Understanding the molecular features that made SARS-CoV-2 a highly infectious virus is crucial for the development of targeted therapies and an effective vaccine.
2020-03-31 Ena et al A novel coronavirus emerges
Revista Clínica Española (English Edition)
IV. Other Currently, there are candidates for MERS-CoV vaccine and there is an initiation of 3 programs to develop vaccines against the 2019-nCoV.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model As the major vaccine target, the S protein has been evaluated in different types of vaccines against infection by CoVs .
2020-04-01 Jain et al Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes
biorxiv
IV. Other Almost all the platforms for vaccine development for SARS-CoV and MERS-CoV have been investigated including the lifeattenuated ones, recombinant viruses, sub-unit protein vaccines, DNA vaccines, Viral vectorbased vaccines, nanoparticle-based vaccines, etc.

Here we have designed a multiepitope-based vaccine for the SARS-CoV-2 using next generation vaccinology approach where the recently available genome and proteome of the SARS-CoV-2 were maneuvered and a potential vaccine candidate was conceived.
2020-07-31 Shereen et al COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses
Journal of Advanced Research
IV. Prevalence Study

In 2001 the samples were isolated from the healthy persons of Hongkong and the molecular assessment showed 2.5% frequency rate of antibodies against SARS-coronavirus.
There is no available vaccine against COVID-19, while previous vaccines or strategies used to develop a vaccine against SARS-CoV can be effective.

8 Efforts to develop animal models and standardize challenge studies

8.0.0.1 Highlights

8.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Andersen et al Discovery and development of safe-in-man broad-spectrum antiviral agents
International Journal of Infectious Diseases
IV. Other On the other hand, these models allow researchers to predict the behavior of viruses in vivo and, therefore, to reduce animal use and in cases where animal models are unavailable to initiate clinical trials.
2020 Gralinski et al Return of the Coronavirus: 2019-nCoV
Viruses
IV. Prevalence Study

The novel CoV (2019-nCoV) was isolated from a single patient and subsequently verified in 16 additional patients .
As such, MERS mouse models of disease required a great deal of time to develop and are limited in the types of manipulations that can be performed .
2020 Wang et al Science in the fight against the novel coronavirus disease
Chin Med J (Engl)
II. Randomized Controlled Trial

They performed a metagenomic analysis of respiratory tract specimens obtained from five patients suffering from the pneumonia in question and identified the virus now known as 2019-nCoV as the causative agent.
The development of neutralizing antibodies is underway, and efforts are also being made to develop a vaccine.
2020 Lim et al The Author's Response: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR
J Korean Med Sci
IV. Other In the meantime we need to make great efforts to develop antiviral agents to treat COVID-19 as well.
2020-02-04 Zhu et al Should, and how can, exercise be done during a coronavirus outbreak? An interview with Dr. Jeffrey A. Woods
J Sport Health Sci
IV. Other Woods: While there has been much progress in understanding the impact of exercise on our immune systems, there is still much we do not know and the challenge is that we have known about these questions for some time but limitations of human experimentation and a dearth of good animal models have hindered progress.
2020-02-13 Liu et al The reproductive number of COVID-19 is higher compared to SARS coronavirus
J Travel Med
IV. Other However, the studies using mathematical methods produce estimates that are, on average, higher.
2020-02-14 Cui et al Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins
biorxiv
IV. Other Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop.
2020-02-17 Ai et al Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China
medrxiv
IV. Prevalence Study

Twenty patients were finally laboratoryconfirmed with NCP, among whom 14 patients were positive for the first admission SARS-COV-2 RT-PCR, 3 patients turned to positive in the second test after the first negative result.
More studies are needed to further validate our findings.
2020-02-23 Zhu et al COVID-19 in Wuhan: Immediate Psychological Impact on 5062 Health Workers
medrxiv
IV. Prevalence Study

6568 individuals were surveyed and 5281 individuals completed the online questionnaire.
Further studies are needed to improve and validate these models.
2020-02-26 Rothan et al The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak
Journal of Autoimmunity
IV. Other Several groups of scientists are currently working hard to develop a nonhuman primate model to study COVID-19 infection to establish fast track novel therapeutics and for the testing of potential vaccines in addition to providing a better understanding of virus-host interactions.
2020-02-27 Park et al Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2
biorxiv
IV. Other Currently, researchers put their best efforts to identify effective drugs for COVID-19.
2020-02-28 Zumla et al Reducing mortality from 2019-nCoV: host-directed therapies should be an option
The Lancet
IV. Other 7, 8 Specific drugs to treat 2019-nCoV will take several years to develop and evaluate.
2020-02-29 Hao et al Infection Dynamics of Coronavirus Disease 2019 (Covid-19) Modeled with the Integration of the Eyring Rate Process Theory and Free Volume Concept
medrxiv
IV. Other However, our method is straightforward and can potentially be used to standardize R 0 calculation.
2020-03-01 Xiang et al Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold- Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19)
medrxiv
IV. Other METHODS: We collect two groups of cases diagnosed with COVID-19 for experiments.
2020-03-02 Zhu et al The novel coronavirus outbreak in Wuhan, China
Glob Health Res Policy
IV. Prevalence Study Scientists all over the world need to understand COVID-19 and discover potentially effective antiviral treatments and vaccines; epidemiologists need to conduct intensive contact investigations; It is important to promote protection knowledge for the general public .
2020-03-02 Banerjee et al Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
iScience
IV. Other Future studies will elucidate on the possibility of leveraging knowledge from studies in bats to develop therapeutic strategies or enhanced therapeutic molecules for alternate mammalian species, such as humans.

Future studies will elucidate on the possibility of 281 leveraging knowledge from studies in bats to develop therapeutic strategies or enhanced 282 therapeutic molecules for alternate mammalian species, such as humans.
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
Vaccine development can be a challenge.
2020-03-03 Song et al An epidemiological forecast model and software assessing interventions on COVID-19 epidemic in China
medrxiv
IV. Prevalence Study The proposed models should work much better for individual provinces, but we did not perform such analyses.
2020-03-05 Li et al Molecular immune pathogenesis and diagnosis of COVID-19
Journal of Pharmaceutical Analysis
IV. Prevalence Study

Virus genome sequencing of five patients with pneumonia hospitalized from December 18 to December 29, 2019, revealed the presence of a previously unknown β-CoV strain in all of them .
These studies are in progress, but it requires months to years to develop the vaccines for SARS-CoV-2.
2020-03-06 Chen et al Caution: The clinical characteristics of COVID-19 patients at admission are changing
medrxiv
IV. Other Patients were assigned into two groups according to their admission date to analyze the differences in patients' features at admission over time.
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other Scientists and physicians worldwide have been conducting a major campaign to understand this new emergent disease and its epidemiology in an effort to uncover possible treatment regimens, discover effective therapeutic agents, and develop vaccines.
2020-03-13 Lei et al Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).
medrxiv
II. Randomized Controlled Trial No adjustments will be made for multiple hypothesis evaluations of safety endpoints.
2020-03-13 Bhagavathula et al Novel Coronavirus (COVID-19) Knowledge and Perceptions: A Survey of Healthcare Workers
medrxiv
III-2. Cross Sectional Control

A total of 529 HCWs participated, 453 of whom completed the study questionnaire (85.6% response rate), including 234 (51.6%) men and 219 (48.3%) women; most of the participants were below 44 years of age (82.4%).
Refinements were made as required to facilitate better comprehension and to organize the questions before the final survey was distributed to the study population.
2020-03-15 Yang et al Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective
Int J Biol Sci
II. Randomized Controlled Trial

systematically reviewed eight randomized controlled trials, and concluded that, by combination with conventional medicine, TCM showed the beneficial effects such as decrease of mortality and relief of symptom, as well as control of fungal infections in patients with SARS.
Ranging from case reports, case series, controlled observational studies and randomized clinical trials, clinical studies aiming to examine the effect of TCM on SARS have been carried out and reported.
2020-03-16 Zhou et al Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
Cell Discov
IV. Other Several national and international research groups are working on the development of vaccines to prevent and treat the 2019-nCoV/SARS-CoV-2, but effective vaccines are not available yet.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other It may take months to even several years for researchers to develop, produce, standardize, evaluate, approve, and commercialize therapeutic agents for COVID-19.
2020-03-19 Qi et al Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
Biochemical and Biophysical Research Communications
IV. Prevalence Study

GSE136103, 4 samples from cirrhotic patients; Spleen and oesophagus, available from Human Cell Atlas, totally 11 cardiac death donors; Bone marrow, GEO Accession No.
Future studies should investigate these signaling pairs in the setting of CoVs infection in patients and animal models.
2020-03-20 song et al Advance of Novel Coronavirus Registration Clinical Trial
medrxiv
IV. Prevalence Study Humans" , and here are two suggestions: undertake experimental projects that match actual capabilities; design of experimental schemes An appropriate research method must be selected based on the nature of the problem to be solved.

As shown in Table 1 , 67.67% of the studies were intervention studies and 25.00% were observational studies.
2020-03-20 OKBA et al SARS-CoV-2 specific antibody responses in COVID-19 patients
medrxiv
III-3. Time Series Analysis

All three COVID-19 patients had reactive antibodies by both the IgG (6/10 serum samples) and IgA (7/10 serum samples) ELISAs (Figure 3) .
However, since various studies will be carried out in different labs, it is crucial to calibrate and standardize assays developed by different labs using well defined standard references as a part of diagnostic assay validation.
2020-03-20 Zhao et al Chinese Public Attention to COVID-19 Epidemic: Based on Social Media
medrxiv
IV. Prevalence Study To fight against COVID-19 and promote the prevention and control of the epidemic, researchers have recently made efforts in various aspects; their research involves epidemiological research 5, 6, 7 , diagnostic methods of the novel coronavirus 8, 9, 10, 11 , clinical characteristics of the disease 12, 13, 14, 15, 16 , characteristics of disease transmission 17, 18, 19 , development of candidate therapies 20, 21, 22 , the identification of animal hosts 23, 24, 25, 26 , etc.
2020-03-20 Belhadi et al A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19
medrxiv
II. Randomized Controlled Trial

Phase IV trials were the most commonly reported study type (n=27, 23%).
Our study underlines the need to register as much details as possible on clinical trials registries during outbreaks in order to inform the development of future trials.

These results might inform the adaptation of existing clinical trials and the development of additional trials.

This highlights the fact that researchers should strive to conduct clinical trials with the most promising candidates, according to in vitro and preclinical in vivo scientific data.
2020-03-20 Fefferman et al Fear, Access, and the Real-Time Estimation of Etiological Parameters for Outbreaks of Novel Pathogens
medrxiv
IV. Prevalence Study

For simplicity 134 sake, we will assume that correct diagnosis and treatment has no bearing on the duration 135 of illness/ recovery time, nor on the rates of transmission from infected to susceptible 136 individuals.
353 354 These models and insights may also be of critical use our collective ongoing efforts to 355 understand and predict the progression of COVID-19.
2020-03-24 Wigginton et al Environmental Engineers and Scientists Have Important Roles to Play in Stemming Outbreaks and Pandemics Caused by Enveloped Viruses
Environ Sci Technol
IV. Other Future studies on enveloped viruses should seek to carefully characterize and even standardize the conditions under which measurements are conducted.
2020-03-24 Davidson et al Characterisation of the transcriptome and proteome of SARS-CoV-2 using direct RNA sequencing and tandem mass spectrometry reveals evidence for a cell passage induced in-frame deletion in the spike glycoprotein that removes the furin-like cleavage site.
biorxiv
IV. Other This cell line is routinely used globally to propagate viruses from clinical samples as well as to generate stocks of virus for academic research, drug susceptibility testing and vaccine challenge studies.
2020-03-26 Al-Quteimat et al SARS-CoV-2 outbreak: How can pharmacists help?
Research in Social and Administrative Pharmacy
IV. Prevalence Study The ID pharmacist can coordinate with the microbiology laboratory for the interpretation of, and action involving, COVID-19 test results, monitor compliance with institutional guidelines, prepare and implement local treatment protocols, monitor and manage drug shortages and help in investigations of new drug applications and uses.
2020-03-27 Yelin et al Evaluation of COVID-19 RT-qPCR test in multi-sample pools
medrxiv
IV. Other We hope that this proof-of-concept will encourage others to develop mathematical and computational tools tailored for the pooling of SARS-CoV-2 tests.
2020-03-29 Srinivasan et al Individualized System for Augmenting Ventilator Efficacy (iSAVE): A Rapidly deployable system to expand ventilator capacity
biorxiv
IV. Other 4) First-in-human trials must be performed to replicate the results from benchtop and animal investigation.
2020-03-30 Dong et al Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling
medrxiv
IV. Computer Model Future work will attempt to develop an approach to detect and visualize the conceptual sub-domains.
2020-03-30 Britton et al Basic prediction methodology for covid-19: estimation and sensitivity considerations
medrxiv
IV. Prevalence Study Many papers use advanced models combined with extensive simulations to analyse and predict the outcome of the ongoing covid-19 pandemic (e.g.
2020-03-31 Wang et al Emergence of SARS-like coronavirus poses new challenge in China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.
2020-03-31 Xu et al Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.
2020-03-31 Tang et al Emergence of a novel coronavirus causing respiratory illness from Wuhan, China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.
2020-03-31 Haixu et al Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.
2020-04-15 Musazzi et al New regulatory strategies to manage medicines shortages in Europe
International Journal of Pharmaceutics
IV. Prevalence Study Considering such critical issues and the latest position papers of stakeholder associations (Various Associations, 2019a,b), the establishment of harmonized metrics to classify the impact of medicine shortage on the National Healthcare Systems is a mandatory step to enhance the cooperation among competent National Authorities of the European countries and to rationalize the efforts to mitigate them.
2020-06-30 Gupta et al Clinical considerations for patients with diabetes in times of COVID-19 epidemic
Diabetes & Metabolic Syndrome: Clinical Research & Reviews
IV. Other Efforts to develop a vaccine are underway, which will be a major tool to contain this epidemic .
2020-07-31 Shereen et al COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses
Journal of Advanced Research
IV. Prevalence Study

In 2001 the samples were isolated from the healthy persons of Hongkong and the molecular assessment showed 2.5% frequency rate of antibodies against SARS-coronavirus.
Recently, mice models and clinical isolates were used to develop any therapeutic strategy against SARS-CoV-2 induced COVID-19 .

9 Efforts to develop prophylaxis clinical studies and prioritize in healthcare workers

9.0.0.1 Highlights

9.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Lim et al The Author's Response: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR
J Korean Med Sci
IV. Other In the meantime we need to make great efforts to develop antiviral agents to treat COVID-19 as well.
2020 Shanmugaraj et al Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development
Pathogens
IV. Prevalence Study The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection.
2020 Schwartz et al Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections
Viruses
IV. Prevalence Study

A case-control study to determine the effects of SARS on pregnancy compared 10 pregnant and 40 non-pregnant women with the infection at the Princess Margaret Hospital in Hong Kong .
Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
Clinical trials have commenced in China to identify effective treatments for 2019-nCoV based on the treatment evidence from SARS and MERS.
2020 Wang et al Science in the fight against the novel coronavirus disease
Chin Med J (Engl)
II. Randomized Controlled Trial

They performed a metagenomic analysis of respiratory tract specimens obtained from five patients suffering from the pneumonia in question and identified the virus now known as 2019-nCoV as the causative agent.
As specific therapies targeting 2019-nCoV are lacking, it may be useful to repurpose drugs already licensed for marketing or clinical trials to treat COVID-19 patients in an emergency response; researchers are actively working to identify such drugs.
2020-02-10 Li et al A qualitative study of zoonotic risk factors among rural communities in southern China
Int Health
IV. Prevalence Study

We aimed to obtain a minimum sample size of 20 participants from each of the three provinces, for a total sample size of over 60 participants.
31 Existing local preliminary programmes and policies around human and animal health, community development and conservation are considered effective resources to begin or continue developing cost-effective strategies to mitigate zoonotic risks.
2020-02-14 Wang et al What to do next to control the 2019-nCoV epidemic?
The Lancet
IV. Other 13 Many efforts, including several clinical trials, such as NCT04246242 and NCT04252664, are in progress to screen existing antiviral drugs to identify those that could be specific and efficient against 2019-nCoV.
2020-02-19 Liu et al Online mental health services in China during the COVID-19 outbreak
The Lancet Psychiatry
IV. Other These findings are important in enabling health authorities to allocate health resources and develop appropriate treatments for medical staff who have mental health problems.
2020-02-19 Zhang et al A Novel Coronavirus (COVID-19) Outbreak A Call for Action
Chest
IV. Prevalence Study

12 In the last 2 weeks of January 2020, thirteen children were diagnosed, fortunately with a mild clinical presentation.
The information produced by this research allows the medical and scientific communities to better understand the transmission of COVID-19, to develop rapid diagnostic tests and efficient epidemiologic control, and to facilitate the development of antiviral therapies and vaccines.
2020-02-26 Rothan et al The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak
Journal of Autoimmunity
IV. Other Therefore, development of methods to identify the various modes of transmission such as feacal and urine samples are urgently warranted in order to develop strategies to inhibit and/or minimize transmission and to develop therapeutics to control the disease.
2020-02-27 Peng et al Outbreak of a new coronavirus: what anaesthetists should know
British Journal of Anaesthesia
IV. Prevalence Study

The median age of infected individuals is between 49 and 56 yr. 1 13 Children are rarely diagnosed with 2019-nCoV, a phenomenon that has not yet been explained.
Hospital infection prevention and control programmes aid with case identification through screening and testing, and they execute isolation infection prevention measures to ensure healthcare settings are safe from infection transmission.
2020-02-27 Park et al Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2
biorxiv
IV. Other Currently, researchers put their best efforts to identify effective drugs for COVID-19.
2020-02-28 Bao et al 2019-nCoV epidemic: address mental health care to empower society
The Lancet
IV. Prevalence Study Health-care workers are also at risk of getting infected, and they carry a large burden in the clinical treatment and public prevention efforts in Chinese hospitals and community settings.
2020-02-28 Zumla et al Reducing mortality from 2019-nCoV: host-directed therapies should be an option
The Lancet
IV. Other 7, 8 Specific drugs to treat 2019-nCoV will take several years to develop and evaluate.
2020-02-28 Jernigan et al Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020
MMWR. Morbidity and Mortality Weekly Report
IV. Other Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines.
2020-03-06 Riou et al Adjusted age-specific case fatality ratio during the COVID-19 epidemic in Hubei, China, January and February 2020
medrxiv
IV. Prevalence Study

The model estimates that a total of 82,300 individuals (95%CrI: 73,000-91,800) were infected in Hubei between 1 January and 11 February 2020.
Clinicians need to know age-and sex-specific mortality among symptomatic patients seeking care to assess prognosis and, in severe situations, prioritize patients with the best expected outcomes.
2020-03-07 Baker et al Preparing for a Surge of Coronavirus Cases
The Joint Commission Journal on Quality and Patient Safety
IV. Other  Organizations should implement a system for evaluation and management of exposed or ill health care workers and support staff that could expose patients, visitors, or other staff.
2020-03-08 Rao et al Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis
medrxiv
IV. Prevalence Study

recently carried out a nationwide analysis of 1,590 patients with laboratory-confirmed COVID-19 and suggested that cancer patients might have a higher infection risk than those without 39 .
This analysis may help to prioritize resources for better prevention of the infection in those susceptible subjects.
2020-03-11 Wong et al Preparing for a COVID-19 pandemic: a review of operating room outbreak response measures in a large tertiary hospital in Singapore
Canadian Journal of Anesthesia/Journal canadien d'anesthésie
IV. Other These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.
2020-03-12 Liu et al Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
ACS Cent Sci
IV. Other Scientists and physicians worldwide have been conducting a major campaign to understand this new emergent disease and its epidemiology in an effort to uncover possible treatment regimens, discover effective therapeutic agents, and develop vaccines.

Researchers have been racing to find possible treatments to save lives and produce vaccines for future prevention.
2020-03-13 Qiao et al What are the risks of COVID-19 infection in pregnant women?
The Lancet
IV. Other More evidence is needed to develop effective preventive and clinical strategies.
2020-03-17 Bedford et al COVID-19: towards controlling of a pandemic
The Lancet
IV. Other Comparative analysis of different quarantine strategies and contexts for their effectiveness and social acceptability Enhance and develop an ethical framework for outbreak response that includes better equity for access to interventions for all countries Promote the development of point-of-care diagnostic tests Determine the best ways to apply knowledge about infection prevention and control in health-care settings in resource-constrained countries (including identification of optimal personal protective equipment) and in the broader community, specifically to understand behaviour among different vulnerable groups Support standardised, best evidence-based approach for clinical management and better outcomes and implement randomised, controlled trials for therapeutics and vaccines as promising agents emerge Validation of existing serological tests, including those that have been developed by commercial entities, and establishment of biobanks and serum panels of well characterised COVID-19 sera to support such efforts Complete work on animal models for vaccine and therapeutic research and development include some identified by the global community and by the Research and Development Blueprint Scientific Advisory Group.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other It may take months to even several years for researchers to develop, produce, standardize, evaluate, approve, and commercialize therapeutic agents for COVID-19.
2020-03-18 Kandel et al Health security capacities in the context of COVID-19 outbreak: an analysis of International Health Regulations annual report data from 182 countries
The Lancet
IV. Prevalence Study 6 No specific antiviral therapies are available, and efforts to dev elop antivirals and a vaccine continue.
2020-03-20 Krengli et al Running a Radiation Oncology Department at the time of coronavirus: an Italian experience
Advances in Radiation Oncology
IV. Other Adopted preventive measures and recommendations are highlighted for patients, professionals and clinical operations to minimize the risk of infection while safely treating cancer patients.
2020-03-20 Zhao et al Chinese Public Attention to COVID-19 Epidemic: Based on Social Media
medrxiv
IV. Prevalence Study To fight against COVID-19 and promote the prevention and control of the epidemic, researchers have recently made efforts in various aspects; their research involves epidemiological research 5, 6, 7 , diagnostic methods of the novel coronavirus 8, 9, 10, 11 , clinical characteristics of the disease 12, 13, 14, 15, 16 , characteristics of disease transmission 17, 18, 19 , development of candidate therapies 20, 21, 22 , the identification of animal hosts 23, 24, 25, 26 , etc.
2020-03-20 Gautret et al Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
International Journal of Antimicrobial Agents
IV. Other Further works are also warranted to determine if these compounds could be useful as chemoprophylaxis to prevent the transmission of the virus, especially for healthcare workers.
2020-03-20 Solaimanzadeh et al Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19)
PMC
IV. Other Matching clinical dispositions can be considered in efforts to develop therapeutic interventions.
2020-03-23 Coelho et al Assessing the potential impacts of COVID-19 in Brasil: Mobility, Morbidity and Impact to the Health System
medrxiv
IV. Prevalence Study The resulting maps should help authorities in their efforts to prioritize actions and if resource allocation to mitigate the effects of the pandemic.
2020-03-24 Luo et al Management of pregnant women infected with COVID-19
The Lancet Infectious Diseases
IV. Other Further research is needed to assess the risk and to produce guidelines for delivery times and methods in patients with COVID-19.
2020-03-25 Prem et al The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study
The Lancet Public Health
IV. Prevalence Study

Each simulation started with 200 or 2000 infectious individuals I 0 , 15 with the rest of the population being in the susceptible state.
The measures put in place to reduce contacts in school and work are helping to control the COVID-19 outbreak by affording health-care systems time to expand and respond.
2020-03-27 Liu et al Mental health considerations for children quarantined because of COVID-19
The Lancet Child & Adolescent Health
IV. Other We propose that paediatric health-care workers should receive
2020-03-27 Wu et al Radiotherapy care during a major outbreak of COVID-19 in Wuhan
Advances in Radiation Oncology
IV. Other Instead, efforts were put in place to develop COVID-19 prevention workflow and standards, to disinfect treatment vaults, and to design and develop appropriate isolation zoning.
2020-03-30 Huang et al Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis
medrxiv
IV. Prevalence Study

In this study, we retrospectively analyzed the clinical characteristics of 97 those patients who progressed to severe pneumonia later and found that five CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Therefore, the most crucial issue is 80 to identify these patients and prioritize their treatment strategy by applying 81 .
2020-03-30 Ansari et al Deliberate release: Plague – A review
Journal of Biosafety and Biosecurity
IV. Other The next steps would be to create a viable vaccine, continue research on novel therapies, distribute rapid diagnostic tests, and raise the awareness of clinicians to the possibility of an attack.
2020-03-30 Xu et al Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study
medrxiv
III-2. Retrospective Cohort

In order to implement the out-of-sample prediction, 1,324 patients were randomly divided into training (1,059 cases) and validation samples (265 cases Table 2) .
Consequently, the right timing for the test will avoid repeated sampling, reduce exposure risk for outpatients and healthcare providers, and improve the efficiency of medical efforts to contain the epidemic.
2020-03-30 Xie et al Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19
medrxiv
III-2. Retrospective Cohort

Second cohort of 151 patients admitted to Jinyintan hospital who were included in a previous study were reused for model validation.
Since early identification and effective treatment can reduce mortality and morbidity as well as relieve resource shortages, there is an urgent need for effective prediction models to identify patients who are most likely to develop respiratory failure and poor outcomes.
2020-03-31 Lai et al Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
International Journal of Antimicrobial Agents
IV. Other All effort s are being made to slow the spread of the illness in order to provide time to better prepare healthcare systems and the general public, to better characterise COVID-19 to guide public-health recommendations, and to develop timely diagnostics, therapeutics and vaccines .
2020-03-31 Tang et al Emergence of a novel coronavirus causing respiratory illness from Wuhan, China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.

Validation of these potential associations in a larger sample, with systematic ascertainment of antibiotic exposure, could further elucidate the potential impact of prophylaxis on development of meningococcal disease among eculizumab recipients.
2020-03-31 Wang et al Emergence of SARS-like coronavirus poses new challenge in China
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.

Validation of these potential associations in a larger sample, with systematic ascertainment of antibiotic exposure, could further elucidate the potential impact of prophylaxis on development of meningococcal disease among eculizumab recipients.
2020-03-31 Xu et al Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.

Validation of these potential associations in a larger sample, with systematic ascertainment of antibiotic exposure, could further elucidate the potential impact of prophylaxis on development of meningococcal disease among eculizumab recipients.
2020-03-31 Haixu et al Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018
Journal of Infection
IV. Prevalence Study

The series included 47 patients, of whom 15 were taking antibiotic prophylaxis at the time of meningococcal disease onset and 32 were not ( Table 1 ).
Veterinary workers should also actively invest in epidemiological investigations to find the natural hosts of these viruses and develop corresponding detection methods.

Validation of these potential associations in a larger sample, with systematic ascertainment of antibiotic exposure, could further elucidate the potential impact of prophylaxis on development of meningococcal disease among eculizumab recipients.
2020-03-31 Li et al The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future
Microbes and Infection
IV. Prevalence Study

11 January 2020 41 patients have been diagnosed to have infection of the novel coronavirus, with 763 close contacts, 7 severe cases and the first death.
First of all, Chinese health authorities conducted an immediate investigation to characterize and control the disease, including isolation of suspected patients, monitoring of contact clinical status of patients, and developing diagnostic and treatment procedures .
2020-03-31 Poh et al Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein
biorxiv
IV. Other These results are essential to guide the design and evaluation of efficient and 131 specific serological assays, as well as help prioritize vaccine target designs during 132 this unprecedented crisis.
2020-04-01 Shayak et al Transmission Dynamics of COVID-19 and Impact on Public Health Policy
medrxiv
IV. Computer Model For impactful epidemic management, societies need to model their strategies, develop an advanced surveillance system for early detection of cases, facilitate implementation of preventive interventions, and enable effective coordination of healthcare professionals, public health authorities, policy makers and government.

10 Approaches to evaluate risk for enhanced disease after vaccination

10.0.0.1 Highlights

10.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Xinguang Chen et al First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model
Global Health Research and Policy
IV. Prevalence Study The clarification also enhanced our analytical approach by adding an exponential model to evaluate the detection rate and to bring more data assessing the responsiveness of the epidemic to the massive interventions.
2020 Du et al Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
Frontiers in Microbiology
III-3. Time Series Analysis Instead, DNA and nanoparticle vaccines maintain strong safety profile; however, the immunogenicity of these vaccines is usually lower than that of virus-or viral vector-based vaccines, often requiring optimization of sequences, components, or immunization routes, inclusion of appropriate adjuvants, or application of combinational immunization approaches (Zhang et al., 2014) .

Antigen dosage, immunization doses, and intervals may significantly affect the immunogenicity of MERS-CoV subunit vaccines.
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
Effective treatment options are essential to maximize the restoration of affected populations to good health following infections.

Studies that examined the mechanisms of diagnostic tests, drug therapy or vaccine efficacy against SARS, MERS and 2019-nCoV were excluded.
2020 Liu et al Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease
Chin Med J (Engl)
IV. Prevalence Study

In the present study, 78 patients with COVID-19 associated pneumonia included 39 males and 39 females.
Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.
2020-01-28 Chan et al Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan
Emerg Microbes Infect
IV. Other These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
2020-02-11 Sarkar et al The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19
biorxiv
IV. Other For this reason, if satisfactory results are achieved in various in vivo and in vitro tests and trials, these suggested vaccine constructs might be used effectively for vaccination to prevent the coronavirus infection and spreading.

Various computational studies of the suggested vaccine constructs revealed that these vaccines might confer good immunogenic response.
2020-02-11 Khan et al Novel coronavirus, poor quarantine, and the risk of pandemic
Journal of Hospital Infection
IV. Other In general, control of the spread of infection uses strategies such as increasing awareness, protective clothing, treatment, and perhaps most importantly vaccination .
2020-02-13 Clifford et al Interventions targeting air travellers early in the pandemic may delay local outbreaks of SARS-CoV-2
medrxiv
IV. Other Delaying local spread will also allow for crucial time to better understand the pathogen and to evaluate effective treatment and prevention measures.
2020-02-14 Wang et al What to do next to control the 2019-nCoV epidemic?
The Lancet
IV. Other 18 The Chinese Government has initiated at least 13 research programmes as an emergency measure to study the different aspects of the outbreak such as the diagnosis, treatment, and prevention of 2019-nCoVassociated disease.
2020-02-23 Zhu et al COVID-19 in Wuhan: Immediate Psychological Impact on 5062 Health Workers
medrxiv
IV. Prevalence Study

6568 individuals were surveyed and 5281 individuals completed the online questionnaire.
Further studies are needed to improve and validate these models.
2020-02-27 Peng et al Outbreak of a new coronavirus: what anaesthetists should know
British Journal of Anaesthesia
IV. Prevalence Study

The median age of infected individuals is between 49 and 56 yr. 1 13 Children are rarely diagnosed with 2019-nCoV, a phenomenon that has not yet been explained.
Hospital infection prevention and control programmes aid with case identification through screening and testing, and they execute isolation infection prevention measures to ensure healthcare settings are safe from infection transmission.
2020-03-03 Zhang et al Potential Interventions for Novel Coronavirus in China: A Systemic Review
Journal of Medical Virology
IV. Other We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers.
2020-03-04 Rao et al Cell-Membrane-Mimicking Nanodecoys against Infectious Diseases
ACS Nano
IV. Other 34 In viral and bacterial infection models, treatment with functionalized liposomes was demonstrated to improve subject survival as well as to reduce the overall infection.
2020-03-05 Johnson et al Potential scenarios for the progression of a COVID-19 epidemic in the European Union and the European Economic Area, March 2020
Euro Surveill
IV. Prevalence Study measles vaccination campaigns) may be affected.
2020-03-05 Li et al Molecular immune pathogenesis and diagnosis of COVID-19
Journal of Pharmaceutical Analysis
IV. Prevalence Study

Virus genome sequencing of five patients with pneumonia hospitalized from December 18 to December 29, 2019, revealed the presence of a previously unknown β-CoV strain in all of them .
There are several vaccination strategies against SARS-CoV, MERS-CoV tested in animals, including a live-attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and proteins vaccines .
2020-03-06 Lombardi et al Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a question needing an answer
Journal of Hospital Infection
IV. Other Moreover, no primary prophylaxis measures (vaccination) nor effective treatments are available.
2020-03-06 Aleta et al Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach
medrxiv
IV. Other This modeling effort is key, as it can contribute to maximize the effectiveness of any protection measures and gain time to develop new drugs or a vaccine to protect the population.
2020-03-08 Oliveiros et al Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases
medrxiv
III-3. Time Series Analysis

Figure 2 depicts the curves obtained for the provinces that at the first time point (23 td of January) had only one or two cases.
Models were evaluated using alpha=0.05.
2020-03-08 Rao et al Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis
medrxiv
IV. Prevalence Study

recently carried out a nationwide analysis of 1,590 patients with laboratory-confirmed COVID-19 and suggested that cancer patients might have a higher infection risk than those without 39 .
Also, it is likely that vaccines may be developed in the near future; in the lack of resources, susceptible groups may be prioritized to receive vaccination to maximize cost-effectiveness.
2020-03-11 Zhou et al Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
The Lancet
III-2. Retrospective Cohort

Before Jan 11, 2020, SARS-CoV-2 RNA detection results were not available in the electronic medical records, from which data for this study were obtained retrospectively; therefore, this study includes 29 of the 41 patients originally reported on.
The prolonged viral shedding provides the rationale for testing novel coronavirus antiviral interventions in efforts to improve outcomes.
2020-03-12 Choi et al Estimating the reproductive number and the outbreak size of Novel Coronavirus disease (COVID-19) using mathematical model in Republic of Korea
Epidemiology and Health
IV. Computer Model The purpose is to estimate and evaluate the effectiveness of preventive measures using mathematical modeling.
2020-03-16 Jain et al Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection
medrxiv
I. Systematic Review

Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion.
All studies evaluating individual symptoms and comorbidities in predicting severe infection (as measured by disease severity criteria, or ICU admission) were included.
2020-03-17 Zheng et al Deep Learning-based Detection for COVID-19 from Chest CT using Weak Label
medrxiv
IV. Other During the procedure of testing, data augmentation strategies were not applied.
2020-03-20 Ahmadi et al Modeling and Forecasting Trend of COVID-19 Epidemic in Iran
medrxiv
IV. Computer Model their relationship to outcomes should be analyzed to evaluate the cost-effectiveness of various diagnostic therapeutic approaches.
2020-03-20 Guan et al Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT
Academic Radiology
IV. Prevalence Study

Among the three patients, the CT images still showed normal lungs in one patient, and GGO in the lower lobes in the other two patients (Fig 5) .
Imaging was evaluated in terms of the following parameters.
2020-03-21 Ong et al COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning
biorxiv
IV. Prevalence Study Therefore, novel strategies are needed to enhance the efficacy and safety of COVID-19 88 vaccine development.
2020-03-23 Milne et al The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis
medrxiv
IV. Other Such models have been used previously to evaluate the effectiveness (and cost-effectiveness) of alternative infectious disease control and containment strategies, including social distancing, vaccination and antiviral drug treatment in an Australian setting.19
2020-03-23 Wen et al Epidemiological and clinical characteristics of COVID-19 in Shenzhen, the largest migrant city of China
medrxiv
IV. Prevalence Study

In total, there were 29 (7.0%) pediatric patients aged below 15 years, of whom 26 were identified by surveillance and 28 were cases from clusters.
Our results can be used to improve the prediction of transmission risk, design and implementation of intervention measures and strategies, and assessments of intervention effectiveness in similar settings.
2020-03-23 To et al Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study
The Lancet Infectious Diseases
III-3. Time Series Analysis

12 of 23 patients included in this study have been reported previously, 6 but their clinical information, viral load by single copy RNA-dependent RNA polymerasehelicase gene, antibody response, or viral genome analysis has not been reported before.
Reliable data for profiles of serial viral load and serum antibody responses are needed urgently to guide antiviral treatment, infection control, epidemiological measures, and vaccination.
2020-03-23 Chen et al SARS-CoV-2: virus dynamics and host response
The Lancet Infectious Diseases
IV. Other 3 Knowledge of virus dynamics and host response are essential for formulating strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19.
2020-03-25 Ji et al Novel decoy cellular vaccine strategy utilizing transgenic antigen-expressing cells as immune presenter and adjuvant in vaccine prototype against SARS-CoV-2 virus
Medicine in Drug Discovery
IV. Prevalence Study Abstract A novel approach modifying cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination) in the prevention of COVID-19 disease is currently being explored.
2020-03-26 Alschuler et al Integrative considerations during the COVID-19 pandemic
EXPLORE
IV. Prevalence Study

Allium sativum (garlic) 42 Quercetin 43 Astragalus membranaceus 44, 45 Mycelium mushroom extracts 46,47 as well as fruiting body extract of Agaricus blazeii 48 Mentha piperita (peppermint) 49 Andrographis paniculata 50 Green tea and green tea extracts 51, 52 Zinc 53 Vitamin A 54 [note: This study found that 25,000iu daily for 4 months in 84 women resulted in lower serum IL-1b and IL-1b/ IL-4 ratios in obese women.
There is a high level of interest in integrative strategies to augment public health measures to prevent COVID-19 infection and associated pneumonia.
2020-03-26 Gavillet et al Acute Leukemia in the Time of COVID-19
Leukemia Research
IV. Prevalence Study The benefit of vaccination against Streptococcus pneumonia, may be worth investigating in clinical trials.
2020-03-26 Tan et al Viral Kinetics and Antibody Responses in Patients with COVID-19
medrxiv
III-3. Time Series Analysis

A total of 1 260 samples from all 67 patients were collected, including 377 nasopharyngeal swab, 221 sputum, 220 stool, 231 urine and 211 plasma samples ( Table 2) .
However, the role of various antibodies relating to disease severity, immunologically directed treatment, and vaccination efficacy, deserves urgent investigation.
2020-03-27 Wei et al How should we implement radiotherapy for cancer patients in China during the endemic period of COVID-19?
Radiotherapy and Oncology
IV. Other To address this dilemma, we need to tailor cancer treatment plans to provide radiotherapy to the patients in greatest need and develop effective protective measures to prevent the spread of COVID-19 during the radiation implementation procedure.
2020-03-27 Yan et al Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in patients with SARS-CoV-2 infection
medrxiv
IV. Prevalence Study

Results: Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment.
Logistic regression analysis was employed to evaluate risk factors associated with prolonged viral shedding.
2020-03-28 Zhai et al The epidemiology, diagnosis and treatment of COVID-19
International Journal of Antimicrobial Agents
III-2. Matched Case Control

Another study later using the travel history and symptom onset of 88 confirmed cases had a similar mean incubation period, which was 6.4 days (95% CI: 5.6-7.7) .
These findings provide the basis for starting further studies on optimizing the design of vaccination strategies for this emerging infection.
2020-03-29 Alfano et al Non-invasive surveys of mammalian viruses using environmental DNA
biorxiv
IV. Other Three different approaches (A, B, C) were used to analyse the viral capture data:
2020-03-30 Xu et al Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study
medrxiv
III-2. Retrospective Cohort

In order to implement the out-of-sample prediction, 1,324 patients were randomly divided into training (1,059 cases) and validation samples (265 cases Table 2) .
A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive.
2020-03-30 Dy et al A COVID-19 Infection Risk Model for Frontline Health Care Workers
medrxiv
IV. Prevalence Study

A doctor doing brief rounds on 10 patients (where each patient is looked upon in at most 30 seconds) or the situation of having 5 patients per minute are equivalent to 10 encounters.
The formulated risk model (see Appendix: Methods) aims to examine the risk factors of virus transmission per day, quantify these risks, estimate the number of new infections, and suggest ways to minimize these risks.

There are several factors that determine the risk of infection:
2020-03-30 Ansari et al Deliberate release: Plague – A review
Journal of Biosafety and Biosecurity
IV. Other The WHO proposes two potential strategies for vaccination: a reactive vaccine to prevent plague during an outbreak and to interrupt the chains of transmission, and a prophylactic vaccine used primarily in endemic areas.
2020-03-30 Sinnott-Armstrong et al Evaluation of Group Testing for SARS-CoV-2 RNA
medrxiv
IV. Prevalence Study We show below that this strategy works to improve upon existing testing and evaluate the benefits across both simulated and real testing data.
2020-03-30 Fan et al Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study
medrxiv
IV. Other Prophylactic administration of common antibiotics may reduce the risk of co-infection.
2020-03-31 Yu et al Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China
Microbes and Infection
IV. Computer Model As the major vaccine target, the S protein has been evaluated in different types of vaccines against infection by CoVs .
2020-03-31 Lai et al Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
International Journal of Antimicrobial Agents
IV. Other The effective option of antiviral therapy and vaccination are currently under evaluation and development.
2020-03-31 Ling et al C-reactive protein levels in the early stage of COVID-19
Médecine et Maladies Infectieuses
IV. Other Clinical monitoring and appropriate treatment strategies were essential to improve case fatality.

11 Assays to evaluate vaccine immune response and process development for vaccines, alongside suitable animal models [in conjunction with therapeutics]

11.0.0.1 Highlights

11.0.0.2 Articles

Date Authors Title LOE(?) & Sample Matches
2020 Pang et al Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine
I. Systematic Review

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened, only four were eventually included in the review.
The systematic searches for diagnosis, therapeutic drugs and vaccines were carried out independently and the key words "drug", "therapy", "vaccine", "diagnosis", "point of care testing" and "rapid diagnostic test" were used in conjunction with the disease key words for the respective searches.

Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak.

Several vaccine candidates are in the pipeline.

Rapid diagnostics, vaccines and therapeutics are key pharmaceutical interventions to limit transmission of respiratory infectious diseases.

Studies that examined the mechanisms of diagnostic tests, drug therapy or vaccine efficacy against SARS, MERS and 2019-nCoV were excluded.

The vaccines in development include viral vector-based vaccine, DNA vaccine, subunit vaccine, virus-like particles (VLPs)-based vaccine, inactivated whole-virus (IWV) vaccine and live attenuated vaccine.
2020 Du et al Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
Frontiers in Microbiology
III-3. Time Series Analysis Taken together, the approaches and strategies in the development of subunit vaccines against SARS and MERS described in this review will provide important information for the rapid design and development of safe and effective subunit vaccines against 2019-nCoV infection.

Similar to DNA or VLP-based vaccines, subunit vaccines are generally safe without causing potential harmful immune responses, making them promising vaccine candidates.

In addition, structure and epitope-based vaccine design has become a promising strategy to improve the efficacy of subunit vaccines.
2020 Amodio et al Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions
Healthcare (Basel)
IV. Prevalence Study Various vaccine strategies against coronavirus, such as using inactivated viruses, live-attenuated viruses, viral vectorbased vaccines, subunit vaccines, and recombinant proteins are under evaluation.
2020 Ralph et al 2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness
Journal of Infection in Developing Countries
IV. Prevalence Study

On 8 January 2020, it was reported that a novel coronavirus had been sequenced from one patient and subsequently identified in some of the other patients with pneumonia , later reported as 15 of the 59 patients .
As vaccine candidates are identified, the requirement of animal models for vaccine development and evaluation will be essential.

Several vaccine platforms exist with the ability to induce protective responses: killed whole virus vaccines; split-virion vaccines; subunit vaccines; live-attenuated viral vaccines; viruslike particle vaccines; nanoparticle vaccines; and nucleic acid vaccines (DNA and RNA).
2020 Wang et al [Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures]
Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns
IV. Other While there is currently no vaccine or effective drugs.
2020 Schwartz et al Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections
Viruses
IV. Prevalence Study

A case-control study to determine the effects of SARS on pregnancy compared 10 pregnant and 40 non-pregnant women with the infection at the Princess Margaret Hospital in Hong Kong .
Safe testing of experimental vaccines in a pregnant population is difficult and, as a result, vaccines are not typically developed with pregnant women in mind.
2020 Zhang et al In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus
Journal of Integrative Medicine
IV. Other While specific vaccines and antiviral agents are the most effective methods to prevent and treat viral infection, there are not yet effective treatments that target the 2019-nCoV.
2020 Shanmugaraj et al Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development
Pathogens
IV. Prevalence Study An effective vaccine should be affordable, and also the production platform should produce suitable vaccine candidates rapidly at low cost, especially during a disease outbreak.
2020-02-11 Sarkar et al The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19
biorxiv
IV. Other Various computational studies of the suggested vaccine constructs revealed that these vaccines might confer good immunogenic response.

Therefore, our present study should help the scientists to develop potential vaccines and therapeutics against the Wuhan Novel Coronavirus 2019.
2020-02-23 Wang et al SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China
medrxiv
IV. Prevalence Study

This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients.
Currently, there are no specific treatments or vaccines for COVID-19.
2020-02-26 Liao et al The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing
medrxiv
IV. Prevalence Study

At the individual levels, we also found the higher T cell clonality was consistently remained in the 3 mild patients as compared to the 3 severe patients ( Figure 4D ), supporting that highly expanded CD8 + T cell participated in resolving the SARS-CoV-2 infection.
Although researchers are racing against time to develop vaccines and test anti-viral drugs in clinical trials , there is no effective prophylactic and clinical treatment for COVID-19 yet.
2020-02-26 Rothan et al The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak
Journal of Autoimmunity
IV. Other Several groups of scientists are currently working hard to develop a nonhuman primate model to study COVID-19 infection to establish fast track novel therapeutics and for the testing of potential vaccines in addition to providing a better understanding of virus-host interactions.

At present, there are no specific antiviral drugs or vaccine against COVID-19 infection for potential therapy of humans.
2020-02-27 Jin et al Structure of Mpro from COVID-19 virus and discovery of its inhibitors
biorxiv
IV. Other Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.
2020-02-29 Wilson et al What goes on board aircraft? Passengers include Aedes, Anopheles, 2019-nCoV, dengue, Salmonella, Zika, et al
Travel Medicine and Infectious Disease
IV. Other Diagnostics have been developed and work on therapeutics and vaccines is underway.
2020-03-03 Tan et al Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study
medrxiv
IV. Other Therefore, we suggested that LYM% should be used as an indicator for evaluating the effectiveness of clinical drugs or therapies.
2020-03-03 Yang et al The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China
Journal of Autoimmunity
IV. Prevalence Study

In Wang's study , of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
A strong public health surveillance system to guide the response to the outbreak is important in the face of a lack of effective therapeutics or vaccines.

Development of animal models that faithfully mimic SARS-CoV-2 infection in humans is critical not only in providing a more refined understanding of the pathogenic mechanisms involved but also to serve as a screening model for potential chemotherapeutic agents and vaccines.
2020-03-04 Memish et al Middle East respiratory syndrome
The Lancet
II. Randomized Controlled Trial

A retrospective study of 136 patients with MERS found that macrolide therapy resulted in no reduction in mortality or faster MERS-CoV RNA clearance compared with those who were not treated with macrolides.
121 Multiple types of vaccine candidates are in development including inactivated whole virus, live attenuated virus, viral vectored vaccines, subunit vaccines, and DNA vaccines.
2020-03-05 Li et al Molecular immune pathogenesis and diagnosis of COVID-19
Journal of Pharmaceutical Analysis
IV. Prevalence Study

Virus genome sequencing of five patients with pneumonia hospitalized from December 18 to December 29, 2019, revealed the presence of a previously unknown β-CoV strain in all of them .
There are several vaccination strategies against SARS-CoV, MERS-CoV tested in animals, including a live-attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and proteins vaccines .
2020-03-12 Wang et al A human monoclonal antibody blocking SARS-CoV-2 infection
biorxiv
IV. Other Vaccines and targeted therapeutics for treatment of this disease are currently lacking.
2020-03-13 Singhal et al A Review of Coronavirus Disease-2019 (COVID-19)
Indian J Pediatr
IV. Prevalence Study

The median age was 8 y 11 mo and in 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China.
A candidate vaccine is under development.
2020-03-15 Yi et al COVID-19: what has been learned and to be learned about the novel coronavirus disease
Int J Biol Sci
IV. Prevalence Study

On February 11, 2020, a multi-center study on 8,866 patients including 4,021 confirmed COVID-19 patients presented a more updated illustration of the epidemic as follows ( UlBi-HX_rHPXa1qHA2bhdA).
Live-attenuated vaccines have been evaluated in animal models for SARS .
2020-03-15 Zheng et al SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat
Int J Biol Sci
IV. Other In addition, great effort should be made on the development of vaccine and antiviral drugs.
2020-03-16 Mehta et al COVID-19: consider cytokine storm syndromes and immunosuppression
The Lancet
IV. Other Current focus has been on the development of novel therapeutics, including antivirals and vaccines.
2020-03-16 Hemida et al The SARS-CoV-2 outbreak from a one health perspective
One Health
IV. Prevalence Study This sequence will have a significant impact on the development of novel diagnostic assays, antiviral drugs, and vaccines against the virus soon.
2020-03-18 Dhama et al COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics
Hum Vaccin Immunother
IV. Other 65 These antibodies could be useful tools also in the development of vaccines, therapeutic drugs, and antiviral inhibitors.

There are no effective vaccines or specific antiviral drugs for COVID-19.
2020-03-18 Kandel et al Health security capacities in the context of COVID-19 outbreak: an analysis of International Health Regulations annual report data from 182 countries
The Lancet
IV. Prevalence Study 6 No specific antiviral therapies are available, and efforts to dev elop antivirals and a vaccine continue.
2020-03-20 Belhadi et al A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19
medrxiv
II. Randomized Controlled Trial

Phase IV trials were the most commonly reported study type (n=27, 23%).
2 To encourage the development of clinical trials that test therapeutics against SARS-CoV-2, the WHO has suggested a number of candidate antiviral agents that have to be tested in clinical trials.
2020-03-20 Jeon et al Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
biorxiv
IV. Other In this study, we screened a panel of FDA-approved drugs to identify antiviral drug candidates for the treatment of COVID-19 and suggest the identified drug candidates may be considered for therapeutic development.

Currently, there is no vaccines or therapeutics available and the patients with COVID-19 are being treated with supportive care.
2020-03-25 Li et al FEP-based screening prompts drug repositioning against COVID-19
biorxiv
IV. Other There are no specific drugs or vaccines against COVID-19, thus effective antiviral agents are still urgently needed to combat this virus.
2020-03-28 Zhai et al The epidemiology, diagnosis and treatment of COVID-19
International Journal of Antimicrobial Agents
III-2. Matched Case Control

Another study later using the travel history and symptom onset of 88 confirmed cases had a similar mean incubation period, which was 6.4 days (95% CI: 5.6-7.7) .
The development of vaccines and therapeutic antibodies against COVID-19 has important implications.
2020-03-30 Zhou et al Clinical features and outcomes of 197 adult discharged patients with COIVD-19 in Yichang, Hubei
medrxiv
IV. Prevalence Study

For the coagulation tests, Prothrombin time (PT) and activated partial thromboplastin time (APTT) were at the normal range in the majority of patients, while fib was above the normal range in the 78 (39.6%) patients, D-dimmer was above the normal range in the 99 (47.2%) patients.
At present, there was no vaccine and antiviral drugs against this disease.
2020-03-30 Dong et al Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling
medrxiv
IV. Computer Model The results also indicate that studies in diagnostics, therapeutics, vaccines, viral genomics, and pathogenesis are urgently needed to minimize the impact of the COVID-19 outbreak.
2020-03-31 Ena et al A novel coronavirus emerges
Revista Clínica Española (English Edition)
IV. Other Currently, there are candidates for MERS-CoV vaccine and there is an initiation of 3 programs to develop vaccines against the 2019-nCoV.
2020-03-31 Deretic et al Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells
biorxiv
IV. Other Currently, there are no approved therapeutics or vaccines for coronavirus diseases.
2020-03-31 Li et al The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future
Microbes and Infection
IV. Prevalence Study

11 January 2020 41 patients have been diagnosed to have infection of the novel coronavirus, with 763 close contacts, 7 severe cases and the first death.
The development of safe, stable vaccines is a huge challenge and vaccines would ideally be broadspectrum, so the research and development of new drugs is a very long process.
2020-04-01 Jain et al Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes
biorxiv
IV. Other Almost all the platforms for vaccine development for SARS-CoV and MERS-CoV have been investigated including the lifeattenuated ones, recombinant viruses, sub-unit protein vaccines, DNA vaccines, Viral vectorbased vaccines, nanoparticle-based vaccines, etc.
2020-07-31 Shereen et al COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses
Journal of Advanced Research
IV. Prevalence Study

In 2001 the samples were isolated from the healthy persons of Hongkong and the molecular assessment showed 2.5% frequency rate of antibodies against SARS-coronavirus.
There is no available vaccine against COVID-19, while previous vaccines or strategies used to develop a vaccine against SARS-CoV can be effective.
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Levels of Evidence in Epidemiology
LevelRating Criteria
IEvidence obtained from a systematic review or meta-analysis of all relevant randomized, controlled trials
IIEvidence obtained from at least one properly designed randomized, controlled trial
III-1Evidence obtained from well-designed pseudorandomized controlled trials (without proper randomization)
III-2Evidence obtained from comparative studies with concurrent controls and allocation not randomized (cohort studies), case-control studies, or interrupted time series with a control group
III-3Evidence obtained from comparative studies with historical control, 2 or more single-arm studies, or interrupted time series without a parallel control group
IVEvidence obtained from descriptive case series, either before testing or before and after testing