Remdesivir and hydroxychloroquine do not show antiviral effects in patients with COVID-19

Research has shown that neither remdesivir nor hydroxychloroquine has an effect on COVID-19 mortality, and now the results indicate that the drugs had no significant effect on the clearance rate of SARS- CoV-2 in oropharyngeal samples.

In May 2020, the FDA has issued an emergency use authorization for remdesivir for severe cases of COVID-19, and the agency then approved the antiviral for adults and children over 12 years of age when treatment for COVID-19 requires hospitalization. In November, based on the results of the WHO solidarity trial, a WHO guidelines committee recommended against using remdesivir in patients hospitalized with COVID-19, regardless of their degree of illness, as it had “no significant effect on mortality, need for mechanical ventilation, time to clinical improvement, and other important outcomes for the patient”.

However, previous reports had not addressed the antiviral effects of remdesivir and hydroxychloroquine, Andreas Barratt-Due, PhD, a researcher in the Department of Immunology at the University of Oslo, told Healio Primary Care. Therefore, Barratt-Due and his colleagues analyzed 185 adults with severe COVID-19 at 23 health centers in Norway. According to the researchers, 181 (mean age, 59.8 years; 62% female; mean BMI, 28 kg / m²; and mean duration of COVID-19 symptoms before hospitalization, 8 days) were included in the comprehensive analysis. Of these 181 patients, 42 received remdesivir, 52 received hydroxychloroquine, and 87 received standard care.

The researchers wrote in Annals of Internal Medicine that, according to the WHO solidarity trial, there were no significant differences between the treatment groups regarding mortality during hospitalization. They found a “marked decrease in the load of SARS-CoV-2 in the oropharynx during the first week overall, with similar decreases and viral loads over 10 days” among the three treatment groups.

Additionally, none of the therapies impacted the extent of respiratory failure or inflammatory biomarkers in plasma or serum.

“The lack of antiviral effect was not associated with the duration of symptoms, the level of viral load, the degree of inflammation or the presence of antibodies against SARS-CoV-2 on admission to the hospital. ‘hospital,’ according to the researchers.

However, the results do not necessarily eliminate the need for remdesivir in patients with COVID-19, Barratt-Due told Healio Primary Care.

Andreas Barratt-Due

“We think remdesivir could be important if it was started very early,” he said. “However, most patients go through the disease without requiring treatment and it would likely be difficult to conduct this study because remdesivir is administered intravenously and therefore requires some kind of patient governance. Thus, we see virtually no window for further studies evaluating remdesivir. ”

Regarding hydroxychloroquine, “there is already massive evidence suggesting the lack of effects and further studies are not needed, ”Barratt-Due said.

He said the findings should “probably [make] FDA reconsiders its “decision on remdesivir. A spokesperson for the agency told Healio Primary Care that, generally speaking, the “FDA does not comment on third-party research, but assesses it as part of the body of evidence to deepen our understanding of a. particular problem and help us in our mission of protecting the public. health.”

Perspective

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Oscar Cingolani, MD

This Annals of Internal Medicine article describes a small but important trial that confirms what we already knew about remdesivir and hydroxychloroquine, also adding relevant mechanistic information: the old drug inhibits the viral replication of SARS-CoV-2 in preclinical studies but does not did not affect the duration, progression of disease or mortality. The latter drug also did not significantly improve outcomes in patients with COVID-19. In addition, the authors found no significant effect of remdesivir or hydroxychloroquine on the clearance rate of SARS-CoV-2 in oropharyngeal samples, nor a significant change in blood inflammatory markers.

The article has certain limitations: the number of patients in the study was small, there was no placebo group and, above all, discharge from the hospital was at the discretion of the attending physician, limiting the average duration of the study. ‘hospitalization to 5 to 6 days – thus shortening the duration of treatment in some patients. Nonetheless, the trial appeared to find no benefit for either drug in hospitalized patients with COVID-19.

Oscar Cingolani, MD

Associate Professor of Medicine, Johns Hopkins School of Medicine

Disclosures: Cingolani does not report any relevant financial disclosure.

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