Antivirals can reduce hospitalizations and deaths from COVID

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Patients with non-severe COVID-19 may avoid progression to hospitalization or death by treatment with nirmatrelvir-ritonavir or molnupiravir, according to a systematic review and meta-analysis.

In trials conducted mainly in unvaccinated patients who had been infected with the Delta variant, treatment with nirmatrelvir-ritonavir was associated with 11.7 fewer deaths per 1000 compared with standard care or placebo.

“While we acknowledge that the data were tested in patients with a different variant, we expect that there may still be relevance for other variants,” study author Tyler Pitre, MD, told Medscape Medical News. “We present the most up-to-date summary of the evidence, which suggests benefits for some of these drugs. We hope you find it helpful.

“The most surprising thing was the lack of efficacy of remdesivir,” he noted. “Remdesivir is currently recommended for non-severe disease, but there was no mortality benefit in our analysis, and there was also low-certainty evidence for other important endpoints, such as hospitalizations and reduced risk of invasive mechanical ventilation”.

The study was published online July 25 in CMAJ.

“Probable” benefits

Pitre and colleagues extracted data from randomized trials comparing antiviral therapies with placebo or standard care from the Epistemonikos COVID-19 LĀ·OVE (Overview of the Evidence) database up to 25 ‘April 2022. Forty-one trials with 18,568 patients with non-severe COVID-19. 19 were included in the analysis. Participants’ ages ranged from 36 to 65 years, and approximately half of the participants were male.

The researchers assumed a baseline risk of 13.3 deaths per 1000 based on the average risk of the placebo group and the standard care group. Molnupiravir and nirmatrelvir-ritonavir reduced the risk of death (by 10.9 fewer deaths per 1,000 and 11.7 fewer deaths per 1,000, respectively) with moderate certainty, compared with placebo or standard care.

In contrast, remdesivir had no effect on mortality risk, nor did sofosbuvir-daclatasvir or emtricitabine-tenofovir (moderate certainty).

The risk of hospitalization was reduced with nirmatrelvir-ritonavir (46.2 fewer admissions per 1,000, high certainty), compared with standard care or placebo. Molnupiravir probably reduced the risk (16.3 fewer admissions per 1,000, moderate certainty) and remdesivir may have reduced the risk (39.1 fewer admissions, low certainty).

In addition, nirmatrelvir-ritonavir probably reduced the risk of hospitalization, compared with molnupiravir (27.8 fewer admissions per 1,000, moderate certainty).

The analysis also showed that molnupiravir probably reduced the need for mechanical ventilation (13 fewer events per 1000, moderate certainty), compared with placebo or standard care, while remdesivir may have reduced the risk of needing mechanical ventilation (11.8 fewer events per 1000, low certainty).

Adverse event rates were very similar for nirmatrelvir-ritonavir and molnupiravir.

A subgroup analysis of two trials of remdesivir found no effect of age or gender on mortality risk. Only one molnupiravir trial reported subgroup data. In this trial, there was no evidence of an effect on hospital admission disease by severity, age or sex.

The analysis will be updated as results from large trials become available, Pitre said.

Current Impact “Unknown”

“Adaptive platform trials and large observational studies offer the best opportunities to generate timely evidence on the efficacy of COVID-19 therapeutics,” write Corinne Hohl, MD, MHSc, associate professor of emergency medicine at the University of British Columbia, Vancouver, and Andrew McRae. , MD, PhD, assistant professor of emergency medicine at the University of Calgary, Alberta, in an accompanying editorial. “These studies can be completed in Canada, but must be supported by Canadian research funders, health care institutions, data custodians, health care providers and patients.”

Commenting on the report for Medscape, Robert M. Grossberg, MD, medical director of the Center for Positive Living/ID Clinic at Montefiore Health System and associate professor of infectious diseases at Albert Einstein College of Medicine, in New York City, said: “This analysis adds support to our current understanding of the COVID-19 antiviral landscape.”

However, he added: “As the authors point out, the studies … were done in unvaccinated participants and before the advent of Omicron. We expect vaccinated individuals to be less likely to progress to severe disease or hospitalization. We also know that these outcomes are less likely with Omicron than with previous variants. We would therefore expect that the impact of these drugs in the current space would be much less, as most patients will do well without either antiviral treatment”.

However, other endpoints, such as duration of illness or duration of viral shedding, could affect transmission and should be considered, Grossberg said. “Ideally, these drugs would be better evaluated directly. This could provide a more robust picture of which drug is superior.

“The overall benefit of either drug in patients vaccinated with the current variant is unknown,” Grossberg concluded.

The study was conducted without external funding. Pitre and Grossberg reported no relevant financial relationships. Hohl has received grants from the COVID-19 Immunity Task Force, the Canadian Institutes of Health Research, Genome BC, the Michael Smith Health Research Foundation, and the Canadian Association of Emergency Physicians. McRae has received grants from the Canadian Institutes of Health Research and Roche Diagnostics Canada and honoraria from Western University and Servier Pharmaceuticals.

CMAJ. Published online July 25, 2022. Full text

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