Nirmatrelvir-ritonavir, remdesivir probably reduce hospitalizations in nonsevere COVID-19
A new systematic review from The BMJ gathered trials in which patients with mild or moderate COVID-19 were randomized to drug treatment versus standard care or placebo to see which medications reduced hospitalization risk or shortened symptoms.
Nirmatrelvir-ritonavir and remdesivir probably reduce risk of hospitalization for COVID-19, and systemic corticosteroids and molnupiravir may do so, according to a systematic review of treatments for nonsevere COVID-19.
Researchers searched various databases, including the World Health Organization's, for clinical trials in which patients with suspected, probable, or confirmed mild or moderate COVID-19 were randomized to drug treatment versus standard care or placebo. Pairs of reviewers independently screened potentially eligible articles, and after duplicate data abstraction, a Bayesian network meta-analysis was conducted. Risk of bias was also assessed. Results were published by The BMJ on May 29.
The researchers found 259 trials, 187 of which were included. Overall, compared with standard care, moderate-certainty evidence showed that nirmatrelvir-ritonavir and remdesivir probably reduce hospitalization (by decreases of 25 [95% CI, 28 to 20] and 21 [95% CI, 28 to 7] per 1,000 patients). Low-certainty evidence showed that molnupiravir and systemic corticosteroids may reduce admissions. The review also found that azithromycin probably reduces time to symptom resolution (mean difference, 4 days; moderate certainty) and that systemic corticosteroids, favipiravir, molnupiravir, and umifenovir probably also reduce duration of symptoms (moderate to high certainty). Only lopinavir-ritonavir increased adverse effects leading to discontinuation.
None of the drugs showed a significant effect over standard care for mild to moderate COVID-19 on the outcomes of mortality, mechanical ventilation, venous thromboembolism, and clinically important bleeding. In additional, several studied interventions “do not seem to result in a benefit for any patient important outcomes, including [angiotensin-converting enzyme inhibitors/angiotensin receptor blockers], aspirin, colchicine, fluvoxamine, hydroxychloroquine, ivermectin, and lopinavir-ritonavir,” the study authors wrote.
They noted that this is their first systematic review and network meta-analysis focused only on nonsevere COVID-19. “We will perform separate network meta-analyses for patients with severe covid-19,” the authors said.
An accompanying editorial praised the study for sifting through “the sheer volume of these evolving data, which can often present conflicting outcomes and variable results,” confuse clinicians, and hinder the standardization practice. However, the editorialists also cautioned clinicians to consider how the results might have been affected by the evolution of COVID-19 care over time and to weigh the risks and benefits of treatment for individual patients.