No reductions seen in 28-day mortality or duration of hospital stay in COVID-19 with lopinavir-ritonavir.

Lopinavir-ritonavir is not associated with reductions in 28-day mortality or duration of hospital stay among patients admitted to the hospital with COVID-19, according to a study published online Oct. 5 in The Lancet.

Peter W. Horby, M.D., Ph.D., and colleagues on behalf of the RECOVERY Collaborative Group conducted a randomized open-label trial to compare treatments with usual care in patients admitted to the hospital with COVID-19. The trial was conducted at 176 hospitals in the United Kingdom. Eligible patients were randomly assigned to either usual standard of care alone (3,424 patients) or usual standard of care plus lopinavir-ritonavir (1,616 patients) for 10 days or until discharge.

The researchers found that 23 and 22 percent of patients allocated to lopinavir-ritonavir and usual care, respectively, died within 28 days (rate ratio, 1.03; 95 percent confidence interval, 0.91 to 1.17; P = 0.60). Across all prespecified subgroups, the results were consistent. There was no significant difference between the groups in the time until discharge from the hospital alive (median, 11 days in both groups) or the proportion discharged from the hospital alive within 28 days (rate ratio, 0.98; 95 percent confidence interval, 0.91 to 1.05; P = 0.53).

In a comment on the same journal by Bin Cao and Frederick G Hayden suggest there is a role of early antiviral treatment for mild cases
of COVID-19 or prophylaxis in high-risk populations after exposure. Given
the efficient replication of SARS-CoV-2 shortly after infection and the association between mortality and viral RNA loads at diagnosis, it is possible that early use of sufficiently potent antiviral drugs would be an important determining factor in clinical outcomes, although few early intervention trials have been completed.

Recent reports indicate that treatment with injected or inhaled recombinant interferon beta or with a human neutralising monoclonal antibody directed to the S protein anti-receptor binding domain, can reduce viral replication and the risk of disease progression in patients with earlier stages of illness.

The Authors conclusion is that early use of easily administered, more
potent antivirals to treat outpatients and prevent transmission of SARS-CoV-2 needs further clinical study. However, antiviral monotherapy for moderately to severely ill patients admitted to hospital with COVID-19
might not be enough. The evaluation of efficacy and safety of combination therapy with antivirals and immunomodulators for severe COVID-19 should be a priority for ongoing and future clinical trials.