The antiviral drugs molnupiravir and nirmatrelvir–ritonavir (Paxlovid), when used to treat non-severe COVID-19, most likely reduce the risk of subsequent progression to hospitalisation and death, according to new research published in CMAJ (Canadian Medical Association Journal).
As most trials have focused on patients with severe or critical COVID-19, researchers conducted a systematic review and meta-analysis to understand the effectiveness of these drugs in treating non-severe COVID-19.
The researchers identified 41 trials involving 18 568 patients with non-severe COVID-19, most of whom were aged 36.5 to 65.5 years. Compared with standard care or placebo, nirmatrelvir–ritonavir likely reduced the risk of hospital admission (46.2 fewer admissions per 1000), and molnupiravir probably reduced the risk (16.3 fewer admissions per 1000).
These findings have implications for healthcare systems and clinical guidelines.
"Our findings suggest that nirmatrelvir–ritonavir may be superior to molnupiravir for some outcomes, which has implications for organizations, such as the [World Health Organization] WHO, that are in the process of developing recommendations addressing molnupiravir and nirmatrelvir–ritonavir," the authors wrote. "Healthcare systems deciding on drug procurement and cost issues need to consider the relative efficacy of nirmatrelvir–ritonavir over molnupiravir."
In a related commentary, the authors pointed out there are challenges in applying these findings to current patients with COVID-19. Several of the trials on which the study is based were conducted among unvaccinated patients who had been infected with the Delta variant. As a significant portion of the population is now vaccinated and many have been infected with the Omicron variant, the medications may be less effective in a real-world setting.
"As the virus and population dynamics evolve, ongoing research is required to inform clinical and policy decisions," wrote Drs. Corinne Hohl, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, BC, and Andrew McRae, University of Calgary, Calgary, Alberta. "Adaptive platform trials and large observational studies offer the best opportunities to generate timely evidence on the effectiveness of COVID-19 therapeutics."