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Yousefifard M, Zali A, Mohamed Ali K, et al. Antiviral therapy in management of COVID-19: a systematic review on current evidence. Arch Acad Emerg Med. 2020 Apr 6;8(1):e45. eCollection 2020. (Systematic review)

Background: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19.

Method: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included.

Results: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV.

Conclusion: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.

Discipline Area Score
Pediatrics (General) 7 / 7
Anesthesiology 6 / 7
Hematology 6 / 7
Emergency Medicine 6 / 7
Pediatric Emergency Medicine 6 / 7
Nephrology 6 / 7
Oncology - General 5 / 7
Infectious Disease 5 / 7
Geriatrics 5 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Hospital Doctor/Hospitalists 5 / 7
Internal Medicine 5 / 7
Cardiology 5 / 7
Hemostasis and Thrombosis 5 / 7
Pediatric Hospital Medicine 4 / 7
Intensivist/Critical Care 4 / 7
Comments from MORE raters

Anesthesiology rater

This is a review of published literature regarding antiviral treatment in COVID-19. As such, it is highly relevant to any healthcare provider. Unfortunately, the information available for review is scant and likely out of date. A manuscript like this one will be much more valuable in a year. At best, this shows the therapies that have been attempted for COVID-19 and will remind clinicians that no proven therapies are yet in existence.

Anesthesiology rater

This analysis presents a review of anti-viral therapy for the corona virus. Most practitioners know that no anti-viral therapy exists. However, the similarity of the virus to previous pandemics and the lack of response to research is surprising. The article is a call to investigate all viruses because it is unclear when it will reappear.

Cardiology rater

Necessary information. I am not an expert, but I'm unsure about the expansiveness of a Medline query that uses only free text search (tiab) and not both free text and MESH.

Emergency Medicine rater

This systematic review evaluates the efficacy of antivirals in COVID-19 and provides a summary of studies conducted for SARS-CoV-1 and MERS-CoV. The authors found only one clinical trial on the efficacy of antivirals for COVID-19, which demonstrated no benefit with lopinavir/ritonavir in terms of viral load or 28-day mortality. All other studies found in the literature review were case reports or case series. No studies were found evaluating lopinavir/ritonavir in SARS-CoV-1 or MERS-CoV. The authors call for further study of antivirals. This reflects the recently released IDSA guidelines.

Emergency Medicine rater

As an Emergency doc, I see patients and their families who are searching for something in which to hope. This analysis lays out what we have suspected - there is NO evidence pointing us one way or the other. I think it's useful information in order to care for patients without harming them.

Family Medicine (FM)/General Practice (GP) rater

This article has a very captivating title, "Antiviral Therapy in Management of COVID-19: a Systematic Review on Current Evidence." Their search strategy, however, reported finding only 1 clinical trial by their definition. This was the trial by Cao et al of "Lopinavir-Ritonavir" vs standard care (NEJM 2020). The reviewers misinterpret the lack of a statistically significant difference as being equivalent to "showing ineffectiveness." This is despite the mortality difference being -5.8% (95% CI = -17.3 to 5.7%).

General Internal Medicine-Primary Care(US) rater

Although this may not be new information, it is important for practitioners in many specialties. It should be distributed.

Geriatrics rater

Simply demonstrates the lack of published evidence on COVID-19 antiviral therapies, a situation that will change dramatically over ensuing months and years.

Hematology rater

Important because it destroys all the hype about promising therapies for COVID-19.

Hemostasis and Thrombosis rater

Seems like a nice summary. Impact is limited by the fact that COVID data changes daily, but methodologically looks reasonable.

Infectious Disease rater

Most of the info is known and none is new.

Intensivist/Critical Care rater

There is only one trial in this systematic review and the rest are case series, from which the review appropriately states you cannot discern any information.

Intensivist/Critical Care rater

Succinct review of the literature on anti-viral therapy for SARS COV-2. Most of the ongoing studies will shed significant light on potentially useful therapy.

Internal Medicine rater

This information was already leaked by the CDC and the results announced on CNN.

Internal Medicine rater

Although an extensive search for studies on anti-retroviral therapy for COVID-19 was performed, there are no RCTs that allow for us to make comfortable treatment decisions on patients with this condition, as we have known since the pandemic began.

Nephrology rater

I agree with the conclusion that "we" should be ready to implement trials since we know these will recur. In addition, cluster randomized trials could be done comparing states in the US who elect to use social distancing vs those who do not to gain more knowledge about whether or not such measures have a positive impact. We know they have a negative impact (economically). Ethically, don't we have an obligation to explore the benefits when we know there are harms?

Oncology - General rater

This review provides a good summary of the lack of high-quality research on antivirals in the management of COVID-19. That said, beyond highlighting the lack of evidence, it does not add much to management.

Pediatric Hospital Medicine rater

We are way too early in the pandemic for a systematic review of treatment options, so the limited findings of this article have no clinical relevance.

Pediatrics (General) rater

This is a rapidly changing climate. The information in this article is likely to be out-of-date quickly. This should be communicated with any update and notify information.

Pediatrics (General) rater

The timely study helps summarize current treatment options for CoVID 19. The lack of solid treatment should inform our public health measures.
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