The Infectious Diseases Society of America updated the treatment portion of its COVID-19 management guidelines, making more specific recommendations for medications. “Back in April when we first issued these guidelines, there were really no medications that were known to be effective against COVID-19, but that has changed,” said Dr Rajesh T Gandhi a member of the guidelines committee.
The panel suggests the use of the antiviral remdesivir (Gilead) over no antiviral treatment for hospitalised patients with COVID-19. For patients with severe COVID-19 who are receiving supplemental oxygen, but who do not require ventilation, the panel suggests that remdesivir be given for five days rather than 10 days.
Several studies showed a benefit with remdesivir, but the recommendations were made based primarily on the ACTT (Adaptive COVID-19 Treatment Trial) conducted by the National Institutes of Health, according to Gandhi, a professor of medicine and Harvard Medical School director of HIV clinical services and education, Massachusetts General Hospital, in Boston.
A preliminary analysis of the trial (ACTT-1) showed a trend in reduction of mortality in the remdesivir treatment arm over placebo (hazard ratio [HR], 0.70; 95% CI, 0.47-1.04).
“This trial rapidly enrolled over 1,000 people around the world with severe COVID-19 at multiple sites, and they did that in the context of the global pandemic. The main finding from ACTT-1 is that remdesivir was associated with more rapid recovery: 11 days versus 15 days in the placebo group. It was a trend toward a lower death rate in the remdesivir group, about 7% was from remdesivir; about 12% in the placebo group, but that was not significant,” Gandhi explained, adding that the benefit was clearest in people requiring supplemental oxygen, but who were not on a ventilator.
Dexamethasone was recommended for hospitalised patients with severe COVID-19, but not for hospitalised patients who do not require supplemental oxygen. “Steroids are used for many medical conditions to reduce inflammation,” Gandhi said, “and COVID-19 has a phase in which we think that the immune response is overactive, is over-exuberant. That overactive immune response leads to excess inflammation, which causes that severe disease.”
The panel considered data from the UK’s RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial that found a reduction in mortality among COVID-19 patients who were severely ill, especially those who were on a ventilator. In the randomised trial, 2,104 patients received dexamethasone 6 mg once daily for 10 days and were compared with 4,321 patients who received usual care alone. Among the usual care alone group, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio [RR], 0.65; 95% CI, 0.48-0.88; P=0.0003) and by one-fifth in other patients receiving oxygen only (RR, 0.80; 95% CI, 0.67-0.96; P=0.0021). There was no benefit for patients who did not require respiratory support (RR, 1.22; 95% CI, 0.86-1.75; P=0.14). On the question of hydroxychloroquine, the panel recommended against its use as routine care for COVID-19 patients, although the drug might be considered in the context of a clinical trial. Dr Shmuel Shoham, also a member of the panel, said more and more evidence is pointing away from the value of hydroxychlo-roquine for COVID-19.
“Despite everybody’s hopes that we would have cheap, easy, well-known drugs – such as chloroquine or hydroxychloroquine or hydroxychloroquine and azithromycin – that those will be available and effective, it just hasn’t panned out yet,” Shoham said, “which is not to say that all the studies are done. But what’s come through is not encouraging that that’s going to be a great option.”
Several recent studies, including the hydroxychloroquine arm of the RECOVERY trial did not find a mortality benefit for the drugs, explained Shoham, who is an associate professor of medicine at Johns Hopkins University School of Medicine and the associate director of Transplant and Oncology Infectious Diseases Centre at Johns Hopkins, in Baltimore.
The panel recommended convalescent plasma in the context of a clinical trial. “Many questions remain regarding the minimal antibody titer required for the plasma to provide benefit, the type of antibodies that plasma should contain to be most protective, and the optimal timing of therapy,” the guidelines committee wrote.
Finally, the panel added a recommendation against the use of famotidine for the sole purpose of treating COVID-19 outside a clinical trial. There are anecdotal reports from China that people who were already taking famotidine, an H2 receptor agonist for acid reflux or peptic ulcer, had improved survival over those who were already taking proton pump inhibitors, but there are not enough data to make a recommendation, the society said.
The guidelines were updated based on the evidence as of 18 June.