Primary studies included in this systematic review

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Wu et al

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Primary study

Unclassified

Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach.

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Journal Journal of translational medicine
Year 2020
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis Broad syntheses (1 reference)

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BACKGROUND: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. METHODS: Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. RESULTS: Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. CONCLUSIONS: The anti-polymerase drugs predicted here-CID123624208 and CID11687749-may be considered for in vitro and in vivo clinical trials.

Publication Thread

LOTUS China (Lopinavir Trial for Suppression of SARS-Cov-2 in China)

This thread includes 5 references

Publication Thread

Chen ZW et al

This thread includes 3 references

Publication Thread

Duan et al

This thread includes 2 references

Primary study

Unclassified

Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019.

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Journal Pharmacotherapy
Year 2020
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis Broad syntheses (1 reference)

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The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit (ICU) admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacological management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immune modulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Primary study

Unclassified

Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China

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Journal medRxiv
Year 2020
Links DOI medRxiv

This article is included in 22 Systematic reviews Systematic reviews (22 references) 2 Broad syntheses Broad syntheses (2 references)

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BackgroundSevere patients with 2019 novel coronavirus (2019-nCoV) pneumonia progressed rapidly to acute respiratory failure. We aimed to evaluate the definite efficacy and safety of corticosteroid in the treatment of severe COVID-19 pneumonia. MethodsForty-six hospitalized patients with severe COVID-19 pneumonia hospitalized at Wuhan Union Hospital from January 20 to February 25, 2020, were retrospectively reviewed. The patients were divided into two groups based on whether they received corticosteroid treatment. The clinical symptoms and chest computed tomography(CT) results were compared. ResultsA total of 26 patients received intravenous administration of methylprednisolone with a dosage of 1-2mg/kg/d for 5-7 days, while the remaining patients not. There was no significant difference in age, sex, comorbidities, clinical or laboratory parameters between the two groups on admission. The average number of days for body temperature back to the normal range was significantly shorter in patients with administration of methylprednisolone when compared to those without administration of methylprednisolone (2.06{+/-}0.28 vs. 5.29{+/-}0.70, P=0.010). The patients with administration of methylprednisolone had a faster improvement of SpO2, while patients without administration of methylprednisolone had a significantly longer interval of using supplemental oxygen therapy (8.2days[IQR 7.0-10.3] vs. 13.5days(IQR 10.3-16); P<0.001). In terms of chest CT, the absorption degree of the focus was significantly better in patients with administration of methylprednisolone. ConclusionOur data indicate that in patients with severe COVID-19 pneumonia, early, low-dose and short-term application of corticosteroid was associated with a faster improvement of clinical symptoms and absorption of lung focus.

Primary study

Unclassified

Short-Term Dexamethasone in Sars-CoV-2 Patients.

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Journal Rhode Island medical journal (2013)
Year 2020
Links Pubmed

This article is included in 1 Systematic review Systematic reviews (1 reference) 1 Broad synthesis Broad syntheses (1 reference)

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BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. METHODS: We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. RESULTS: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. CONCLUSIONS: A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.

Primary study

Unclassified

Novel coronavirus treatment with ribavirin: Groundwork for evaluation concerning COVID-19.

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Authors Khalili JS , Zhu H , Mak A , Yan Y , Zhu Y
Journal Journal of medical virology
Year 2020
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis Broad syntheses (1 reference)

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Confronting the challenge of the outbreak of COVID-19 should sharpen our focus on global drug access as a key issue in anti-viral therapy testing. The testing and adoption of effective therapies for novel coronaviruses is hampered by the challenge of conducting controlled studies during a state of emergency. The access to direct anti-viral drugs such as ribavirin that have an existing inventory and reliable supply chain may be a priority consideration for therapies developed for the 2019-nCoV infection outbreaks and any strain variants that may emerge. Based on the direct anti-viral activity of ribavirin against 2019-nCoV in vitro and evidence for potency enhancement strategies developed during the prior SARS and MERS outbreaks, ribavirin may significantly impact our ability to end the lingering outbreaks in China and slow outbreaks in other countries. The apparent COVID-19 pandemic provides an opportunity to follow dosage guidelines for treatment with ribavirin, test new therapeutic concepts, and conduct controlled testing to apply the scientific rigor required to address the controversy around this mainstay of anti-viral therapy. This article is protected by copyright. All rights reserved.

Primary study

Unclassified

Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience.

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Journal Antiviral therapy
Year 2018
Links Pubmed DOI

This article is included in 5 Systematic reviews Systematic reviews (5 references) 1 Broad synthesis Broad syntheses (1 reference)

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BACKGROUND: The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS: Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS: Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.