Drugs for the Prevention and Treatment of COVID-19 and its Complications
Fall 2020 Report
Statement by the Lincei Committee on Covid-19 
Summary
The COVID-19 Committee of the Lincei Academy has reviewed the evidence for the efficacy and safety of repurposed and new drugs for the prevention and treatment of COVID-19 and its complications, as well as the safety of some concomitant medications. A number of pharmacological strategies could theoretically prevent the entry of SARS-CoV-2 into target cells and are currently being evaluated for efficacy and safety. These include neutralizing antibodies against the SARS-CoV-2 spike protein, a soluble recombinant form of the SARS-CoV receptor angiotensin-converting enzyme (ACE)2, and drugs inhibiting the activity or expression of the transmembrane protease serine 2 (TMPRSS2) required for the spike protein proteolytic cleavage. Although ACE inhibitors and angiotensin-receptor blockers (ARBs) may enhance ACE2 gene expression, an effect that would increase the availability of receptor molecules for SARS-CoV-2 entry, there is no evidence that these commonly used drugs might be harmful (or even beneficial) in patients with COVID-19. Therefore, persons with COVID-19 who are prescribed ACE inhibitors or ARBs for cardiovascular disease (or other indications) should continue these medications; moreover, these drugs are not recommended outside of the setting of a randomized clinical trial (RCT). Remdesivir was identified early as a promising therapeutic candidate for COVID-19 because of its ability to inhibit SARS-CoV-2 in vitro. A recent double-blind, placebo-controlled RCT of intravenous remdesivir in 1,063 adults hospitalized with COVID-19 with evidence of lower respiratory tract involvement demonstrated that remdesivir was superior to placebo in shortening the time to recovery in this setting. Based on these findings the US Food and Drug Administration (FDA) has made remdesivir available under an emergency-use authorization (EUA) for the treatment of adults and children with severe COVID-19 disease (May 1st), followed by approval for use in adults and pediatric patients requiring hospitalization (October 22nd). Earlier, the FDA had also issued an EUA allowing the temporary use of hydroxychloroquine (HCQ) and chloroquine (CQ) during the COVID-19 pandemic for treatment of the virus in hospitalized patients when clinical trials are not available, or participation is not feasible. This decision was largely based on mechanistic considerations and political pressure. Subsequent observational studies and a limited number of RCTs have not substantiated the clinical efficacy of these antimalarial drugs, while confirming their dose-dependent cardiac toxicity. At present, the US National Institutes of Health (NIH) COVID-19 Treatment Guidelines recommend against the use of CQ or HCQ for the treatment of COVID-19, except in a clinical trial. Early in the course of the SARS-CoV-2 pandemics, it was claimed that nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, could aggravate the infection by masking its symptoms. However, after review of the evidence, the WHO and EMA advisories have been withdrawn. Therefore, until we have robust evidence, patients in chronic pain should continue to take their NSAIDs rather than turn to opiates. Complement inhibition has been proposed as a potential target in limiting tissue inflammation associated with COVID-19. The results of ongoing RCTs are needed to establish the therapeutic potential of C3 or C5 inhibition in COVID-19, and to characterize which patients may benefit the most. Finally, dysregulation of the coagulation cascade and fibrinolytic system is emerging as an important pathophysiologic component of COVID-19. Largely based on observational studies, the International Society on Thrombosis and Haemostasis (ISTH) suggested measuring D-dimer, prothrombin time and platelet count in all COVID-19 patients. ISTH also recommends that all COVID-19 patients admitted to hospital be treated with prophylactic doses of low-molecular-weight heparin, unless contraindicated. Additional RCTs of several antithrombotic agents are currently ongoing. The benefit of corticosteroids in the treatment of COVID-19 has been established in large clinical trials in hospitalized critically ill patients, showing a significant reduction of mortality as compared to those allocated to usual care. The usefulness of dexamethasone in patients with severe pulmonary complications of COVID-19 infection has been confirmed by a recent WHO meta-analysis.
30 November 2020
Responsibility for the information and views expressed in this document lies solely with the Covid-19 Committee.
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June 2020