Drug Treatment for COVID-19: A Quick

Summary for PCPs

Laurie Scudder, DNP, NP

July 15, 2020

Find the latest COVID-19 news and guidance in Medscape's  Coronavirus Resource Center.

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.

Hydroxychloroquine

Initial data suggested that HCQ and chloroquine, sometimes in combination with azithromycin, had some
degree of efficacy in treating COVID-19. But those studies were rapidly followed by newer data from
observational trials, suggesting that the drugs were not only without benefit but also could be dangerous in
some patients. After 2 months of controversy, the FDA revoked the emergency use authorization it had
previously granted for use of these agents in inpatient settings.

The matter seemed to be put to bed until early July when the Henry Ford Hospital released results of
a retrospective, observational trial of HCQ with azithromycin that concluded that the combination, if given within
the first 2 days of hospital admission, reduced COVID-19 mortality.

Trials of HCQ as preventive therapy are ongoing, though a randomized trial published in early June found that
the drug was ineffective as prevention and that side effects were common.

Bottom line on HCQ. While some continue to tout its benefit, particularly if given early in the course of
infection, there is little evidence at this time to support its use at any stage of illness. Stay current on HCQ.

Other Antimicrobials

In the race to find an effective therapy, clinicians around the world have launched trials of a wide range of
agents, with almost universally disappointing results.

Azithromycin. While some initial trials of azithromycin in combination with HCQ were promising, later results
have not held up and major cardiology organizations now warn against the combination. There are no
recommendations for use of this antimicrobial.

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.