Infectious Disease

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

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Research showed that neither remdesivir nor hydroxychloroquine had an effect on COVID-19 mortality, and now the results suggest that the drugs did not have a significant effect on SARS-CoV-2 clearance in oropharyngeal samples.

In May 2020, the FDA granted emergency approval for remdesivir for severe cases of COVID-19, and the agency later approved the antiviral for adults and children over 12 years old when treatment for COVID-19 requires hospitalization. In November, based on the results of the WHO solidarity study, a WHO guidelines committee recommended the use of remdesivir in patients hospitalized with COVID-19, regardless of how sick they are, as it “has no significant effect on mortality , mechanical ventilation, time to clinical improvement and other results important to the patient. ”

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

The researchers wrote in the Annals of Internal Medicine that in line with the WHO Solidarity Study, there were no significant differences between treatment groups in terms of in-hospital mortality. They found a “significant decrease in SARS-CoV-2 exposure in the oropharynx during the first week overall with similar decreases and 10-day viral loads” among the three treatment groups.

In addition, none of the therapies affected the extent of respiratory failure or the biomarkers of inflammation in plasma or serum.

“The lack of antiviral effect was not linked to the duration of symptoms, the level of the viral load, the degree of inflammation or the presence of antibodies against SARS-CoV-2 at hospital admission,” said the researchers.

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

Andreas Barratt-Due

“We believe remdesivir could be significant if 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 given intravenously and therefore requires some kind of patient guidance. Therefore, we hardly see a window for further studies to evaluate remdesivir. ”

With regard to hydroxychloroquine, “there is already massive evidence that there is no effect and no further study is needed,” said Barratt-Due.

He said the results should “probably” [make] the FDA is reconsidering its “decision regarding remdesivir. An agency spokesperson told Healio Primary Care that “the FDA generally does not comment on third-party research, but rather evaluates it as part of the evidence to improve our understanding of a particular topic and to aid our mission to protect the public.” Health.”

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Oscar Cingolani, MD

This Annals of Internal Medicine paper describes a small but important study that confirms what we already knew about remdesivir and hydroxychloroquine, and also adds relevant mechanistic information: The former drug inhibits viral replication of SARS-CoV-2 in preclinical studies, however, did not affect COVID-19 length of hospital stay, disease progression, or mortality. The latter drug also failed to significantly improve outcomes in patients with COVID-19. In addition, the authors found neither a significant effect of remdesivir nor of hydroxychloroquine on the rate of SARS-CoV-2 clearance in oropharyngeal samples, nor a significant change in the markers of inflammation in the blood.

The paper has some limitations: the number of patients in the study was small, there was no placebo group, and most importantly, discharge from hospital was at the discretion of the attending physician, which limited the average length of hospital stay to 5 to 6 days – hence a reduction in the duration of treatment in some patients Still, the study did not appear to find any benefit for either drug in hospitalized patients with COVID-19.

Oscar Cingolani, MD

Associate Professor of Medicine, Johns Hopkins School of Medicine

Disclosure: Cingolani does not report any relevant financial information.

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