Drug Treatment for COVID-19: A Quick Summary for PCPs

Information about COVID has evolved so quickly that it can be difficult for clinicians to feel confident that they are staying current. These summaries include links to our COVID-19 FAQ, which is constantly updated to make sure you have the latest information.

While treatment for COVID-19 outside of the hospital setting is currently limited to supportive therapy, over 1000 clinical trials are underway looking at a range of drug treatments. Here is a quick summary for primary care clinicians of the current state of evidence.

Remdesivir

Much-anticipated results from the National Institute of Allergy and Infectious Diseases' clinical trial of remdesivir, published in May, confirmed preliminary results suggesting that the drug shortens the disease course for hospitalized COVID-19 patients. That earlier report resulted in the US Food and Drug Administration (FDA) issuing an emergency use authorization for the drug. Drugmaker Gilead subsequently released results from the sponsored, randomized phase 3 SIMPLE trial, which found that a 5-day course of the drug improved outcomes among patients hospitalized with COVID-19 who did not need ventilation. The National Institutes of Health said that the most benefit was in patients on oxygen who did not require ventilation.

Remdesivir should be the "standard of care," according to Dr Anthony Fauci, though Dutch investigators have cautioned that it can be associated with rare but severe liver complications.

Bottom line on remdesivir. Remdesivir is administered intravenously, limiting its use to hospitalized patients. However, phase 1 trials of an inhaled nebulized version were initiated in late June 2020 to determine whether remdesivir can be used on an outpatient basis and at earlier stages of disease. The FDA has warned against use of remdesivir in combination with hydroxychloroquine (HCQ) . Stay current on remdesivir.

Dexamethasone

A cheap and widely available steroid roared to international attention in June with the announcement by British researchers that the RECOVERY trial involving over 6000 patients had been halted early due to positive results. The investigators reported that dexamethasone reduced death rates by about a third among severely ill hospitalized COVID-19 patients. Initial reaction in the United States was mixed.

While a number of clinicians indicated that the results confirmed their own experience, others were wary of embracing the study results prior to peer review. That may change, however, with the announcement by the Infectious Diseases Society of America (IDSA) that the drug will now be incorporated into COVID-19 treatment guidelines. Dexamethasone, or an equivalent steroid such as methylprednisolone or prednisone, is recommended for hospitalized patients who require supplemental oxygen, mechanical ventilation, or extracorporeal mechanical oxygenation.

Bottom line on dexamethasone. While corticosteroids are not generally recommended for treatment of COVID-19 or any viral pneumonia, the UK RECOVERY trial changed that. IDSA guidelines include low-dose dexamethasone (6 mg orally or intravenously daily for 10 days) in patients requiring respiratory support. At present, the World Health Organization has cautioned clinicians to reserve use for severely ill patients. Stay current on dexamethasone.

Antiviral agents. The UK-based RECOVERY trial examined other drugs in addition to dexamethasone, concluding that the combination of lopinavir and ritonavir had no benefit in hospitalized patients. A Japanese trial of favipiravir, marketed as Avifavir, determined that patients given the drug early in the trial showed more improvement than those who received delayed doses, but the results did not reach statistical significance. Trials of other antivirals are ongoing.

A Grab Bag of Other Drugs

Convalescent plasma. While a very small Chinese pilot study of convalescent plasma reported in April that its use in severely ill COVID-19 patients raised antibody titers, reduced viral load, and led to symptom improvement, other studies have not yet shown it to be effective. The FDA has approved its use in patients with serious or immediately life-threatening infection.

Colchicine. An open-label, randomized trial currently underway in Greece has reported that hospital course was slightly shorter and the time to clinical deterioration improved in patients treated with colchicine, although there were no significant differences between treated and untreated groups in cardiac and inflammatory biomarkers.

Nitric oxide. Inhaled nitric oxide was studied as a supportive measure for patients with SARS-CoV-1 infection in 2004. It was found to reverse pulmonary hypertension, improve severe hypoxia, and shorten the length of ventilatory support. A phase 2 study is underway in patients with COVID-19, with the goal of preventing disease progression in those with severe acute respiratory distress syndrome.

Zinc. Initial trials of HCQ often studied it in combination with azithromycin and zinc. While some studies have suggested that zinc may be somewhat effective in treatment of upper respiratory infections, some of which are caused by coronaviruses, the National Academies of Sciences, Engineering, and Medicine cautions that there is no evidence to suggest that the supplement has a role in the treatment or prevention of COVID-19.

Monoclonal antibodies. The use of human antibodies is being investigated by a number of teams around the world. Eli Lilly has reported positive interim results of its trials of monoclonal antibodies, and anticipates FDA review and possible approval by September. European trials of another antibody could begin as early as this summer. And trials of a third agent are planning to start in August in Singapore.