Remdesivir, hydroxychloroquine fail to show antiviral effects in patients with COVID-19
Research has shown that neither remdesivir nor hydroxychloroquine had any effect on COVID-19 mortality, and now findings indicate that the drugs had no significant effect on the rate of SARS-CoV-2 clearance in oropharyngeal samples.
In May of 2020, the FDA issued an emergency use authorization for remdesivir for severe cases of COVID-19, and the agency later approved the antiviral for adults and children aged older than 12 years when treatment of COVID-19 requires hospitalization. In November, based on the results of the WHO Solidarity Trial, a WHO guideline committee recommended against the use of remdesivir in patients hospitalized with COVID-19, regardless of how sick they are, because it had “no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes.”
The quote is: "The trial did not seem to find any advantage for either medication in hospitalized patients with COVID-19." The source of the quote is: Oscar Cingolani, MD.
However, earlier reports failed to address the antiviral effects of remdesivir and hydroxychloroquine, Andreas Barratt-Due, PhD, a researcher in the immunology department at the University of Oslo, told 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 were administered remdesivir, 52 received hydroxychloroquine and 87 were provided with standard of care.
The researchers wrote in Annals of Internal Medicine that, consistent with the WHO-Solidarity Trial, there were no significant differences among the treatment groups regarding mortality during hospitalization. They found a “marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads” among the three treatment groups.
Also, neither therapy impacted the extent of respiratory failure or biomarkers of inflammation in plasma or serum.
“The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance,” according to the researchers.
However, the findings do not necessarily eliminate the need for remdesivir in patients with COVID-19, Barratt-Due told Healio Primary Care.
Andreas Barratt-Due
“We believe that remdesivir might be of importance if started very early,” he said. “However, most patients go through the disease without requiring any treatment and it would probably be difficult to conduct this study as remdesivir is administered intravenously and thus requires some kind of patient governance. Thus, we hardly see any window for further studies evaluating remdesivir.”
Regarding hydroxychloroquine, “there is already massive evidence suggesting lack of effects and further studies are not required,” Barratt-Due said.
He said the findings should “probably [make] the FDA reconsider its decision” regarding remdesivir. An agency spokesperson told Healio Primary Care that, generally speaking, the “FDA does not comment on third-party research, but evaluates it as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
PERSPECTIVE
Oscar Cingolani, MD
This Annals of Internal Medicine paper describes a small yet important trial that confirms what we already knew about remdesivir and hydroxychloroquine, also adding relevant mechanistic information: The former medication inhibits SARS-CoV-2 viral replication in preclinical studies but did not affect COVID-19 hospital stay length, progression of the disease or mortality. The latter medication also failed to significantly improve outcomes in patients with COVID-19. In addition, the authors found no significant effects of either remdesivir or hydroxychloroquine on the rate of SARS-CoV-2 clearance in oropharyngeal samples, nor a significant change in blood inflammatory markers.
The paper has some limitations: the number of patients in the study was small, there was no placebo group, and importantly, hospital discharge was at the discretion of the treating physician, limiting the average duration of hospitalization to 5 to 6 days — therefore shortening the duration of treatment in some patients. Nonetheless, the trial did not seem to find any advantage for either medication in hospitalized patients with COVID-19.
Oscar Cingolani, MD
Associate professor of medicine, Johns Hopkins School of Medicine
July 13, 2021
https://www.healio.com/
