Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.
Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.
Current Clinical Treatment Experience and Recommendations
The published clinical treatment experience, outside the few clinical trials mentioned, mostly consists of descriptive reports and case series from China and other countries affected early in this pandemic. Therefore, outcomes including case-fatality rates must be interpreted with caution given the presence of confounding and selection bias as well as the shifting demographics, testing, and treatment approaches. Table 2 summarizes the clinical severity, complications, treatments, and clinical outcomes from early reported COVID-19 case series.
The current Centers for Disease Control and Prevention guidance for clinical care of patients with COVID-19 (as of March 7, 2020) highlights that no specific treatment for COVID-19 is available, and emphasizes that management should include “prompt implementation of recommended infection prevention and control measures and supportive management of complications.”96 The guidance from the Centers for Disease Control and Prevention specifically mentions that corticosteroids should be avoided unless indicated for other reasons. Investigational therapeutics, specifically remdesivir, are mentioned as options through either compassionate use or ongoing clinical trials.
Similarly, the current World Health Organization (WHO) clinical management guidance document (as of March 13, 2020) states “there is no current evidence to recommend any specific anti-COVID-19 treatment for patients with confirmed COVID-19.”97 The guidance emphasizes the role of supportive care based on severity of illness, ranging from symptomatic treatment for mild disease to evidence-based ventilatory management for ARDS and early recognition and treatment of bacterial infections and sepsis in critically ill patients. They recommend to “not routinely give systemic corticosteroids for treatment of viral pneumonia outside clinical trials” and state “investigational anti-COVID-19 therapeutics should be used only in approved, randomized, controlled trials.” In this regard, the WHO recently announced plans to launch a global “megatrial” called SOLIDARITY with a pragmatic trial design that will randomize confirmed cases into either standard care or 1 of 4 active treatment arms (remdesivir, chloroquine or hydroxychloroquine, lopinavir/ritonavir, or lopinavir/ritonavir plus interferon-β) based on local drug availability
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