In light of evolving knowledge about SARS-CoV-2, the Infectious Diseases Society of America (IDSA) has updated guidelines for treating coronavirus 2019 (COVID-19), the illness caused by SARS-CoV-2 infection.

Given research into SARS-CoV-2 is taking place at unprecedented speed, the panel of IDSA experts had to decide on current best practices using science which is still in motion.

Recent updates include:

1. New recommendations on the use of remdesivir.

2. Revised recommendations on hydroxychloroquine and hydroxychloroquine/azithromycin combination therapy.

3. New recommendations for famotidine.

4. Revised recommendations concerning convalescent plasma for treatment of COVID-19.

Remdesivir

Remdesivir is an antiviral which has drawn attention due to demonstrable in vitro activity against a range of RNA viruses, including coronaviruses closely related to SARS-CoV-2.

Last month, the US Food and Drug Administration recently authorized remdesivir for emergency use after a mostly-positive string of recent studies.

For patients with severe COVID-19, the IDSA panel suggests remdesivir over no antiviral treatment. Guideline authors noted that remdesivir appears to demonstrate maximal benefit in those with severe COVID-19 on supplemental oxygen rather than in patients on mechanical ventilation or extracorporeal mechanical oxygenation.

For patients with severe COVID-19 on supplemental oxygen but not on mechanical ventilation, the recommended treatment course is 5 days of remdesivir rather than 10 days. However, in patients on mechanical ventilation, the advised duration of treatment is 10 days.

Given limited evidence across severity, the panel pointed to a knowledge gap when assessing whether greater benefit could be attained for patients with less severe disease. The panel agreed, though, that “the reported data supported the prioritization of remdesivir among persons with severe but not critical COVID-19.”

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Hydroxychloroquine:

The new guidelines emphasize caution when it comes to hydroxychloroquine, which was a promising therapy proposal but has since fallen out of favor due to the prolonged absence of proof of benefit outside of the lab and in human populations.

“The guideline panel recommends that, because of uncertainty regarding its risks and benefits, the use of HCQ should be only in the context of a clinical trial. Because of the potential for toxicity, the panel suggests against HCQ+AZ combination outside of a clinical trial,” authors wrote.

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Famotidine

Famotidine, an antihistamine and antacid, has drawn attention due to positive anecdotes primarily drawn from sources in China.

According to a small body of evidence, patients infected with SARS-CoV-2 who were receiving famotidine had improved survival relative to those receiving proton pump inhibitors.

However, as IDSA guideline authors point out, there is no predominant theory even describing a mechanism for how famotidine would work against COVID-19.

“One theory is that famotidine, like many other compounds, binds and therefore inhibits the coronavirus main protease, 3C-like main protease,” study authors offered.

In a cohort study the team identified, 84 patients treated with famotidine were compared against 1536 patients not receiving treatment the drug. Famotidine may decrease the composite outcome of death or intubation, but evidence is very uncertain.

The panel ultimately recommended against use of famotidine outside clinical trials, but encouraged further scientific exploration.

Convalescent Plasma

On convalescent plasma, the panel concluded that the overall certainty of evidence is low and raised the risk of bias and imprecision.

According to the guidelines, plasma transfusion failed to show or to exclude a beneficial or detrimental effect on mortality across studies. Receipt of COVID-19 plasma may reduce the odds of worsening oxygenation (adjusted odds ratio: 0.86; 95% CI: 0.75, 0.98; very low certainty of evidence).

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Corticosteroids

There were no changes in recommendations concerning corticosteroids, despite promising dexamethasone results.

Contagion^® Editor-in-Chief Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS, was involved in preparing the updated guidelines. Gallagher commented on the matter, pointing toward the omission as an understandable sign of the times.

No change in corticosteroid recommendation, but this was before the RECOVERY preprint was made available… yesterday. COVID science moves quickly! 3/ pic.twitter.com/U9LHJ3ctnZ

— Jason Gallagher (@JGPharmD) June 23, 2020

The guidelines are available on the IDSA website.