TOPLINE:

Antiviral treatment with remdesivir and/or nirmatrelvir/ritonavir within 3 days of hospital admission was associated with a significant reduction in mortality among patients hospitalised with acute SARS-CoV-2 infection during the Omicron era, with the greatest benefit seen among unvaccinated patients without prior infection.

METHODOLOGY:

• Investigators in Sweden conducted a retrospective population-based cohort study using linked registry data to evaluate the efficacy of antiviral treatments — remdesivir and/or nirmatrelvir/ritonavir — among 4016 patients hospitalised with acute SARS-CoV-2 infection (median age, 75 years; 54.1% men) during the Omicron era from December 2021 to April 2023.
• Overall, 771 patients who received antiviral treatment (remdesivir only, n = 651; nirmatrelvir/ritonavir only, n = 105; and both drugs, n = 15) at hospital admission or within 3 days thereafter were compared with 3245 patients who did not receive antiviral treatment; the median duration of antiviral treatment was 4 days.
• Patients had to have an indication of diagnosis and a positive polymerase chain reaction test for SARS-CoV-2 obtained between 2 days before and 2 days after the date of hospital admission.
• The primary outcome was 30-day all-cause mortality, and the secondary outcome was 90-day all-cause mortality from the date of hospital admission. Safety outcomes included new-onset kidney failure, liver failure, and/or cardiac arrhythmia occurring between days 2 and 30 of hospitalisation.

TAKEAWAY:

• Antiviral treatment showed a trend towards reducing 30-day all-cause mortality (adjusted risk ratio [aRR], 0.80; 95% CI, 0.62-1.01) and was associated with a 22% lower risk for 90-day all-cause mortality (aRR, 0.78; 95% CI, 0.63-0.97).
• The benefit was greatest among unvaccinated patients without prior infection who had a 62% lower risk for 30-day mortality compared with that among vaccinated patients (aRR, 0.38; 95% CI, 0.18-0.67).
• Safety analyses showed no significant effects of antiviral treatment on kidney function, liver function, and/or cardiac rhythm during the first 30 days of hospitalisation.

IN PRACTICE:

"The effect of treatment was greater in those without previous immunity against SARS-CoV-2 infection, suggesting this group should be prioritized for treatment," the investigators reported.

SOURCE:

This study was led by John Karlsson Valik, Karolinska Institutet, Stockholm, Sweden. It was published online on September 21, 2025, in Clinical Microbiology and Infection.

LIMITATIONS:

Baseline differences were observed between treated and untreated patients in the unweighted sample, which might have biased the results towards the null. Unmeasured indication bias could not be excluded. Pooling both drugs in the primary analysis may have concealed drug-specific effects, and this study was underpowered to evaluate nirmatrelvir/ritonavir alone or to directly compare the two agents.

DISCLOSURES:

This study received support from the Swedish Research Council and the EuCare Project funded by the European Union's Horizon Europe Research and Innovation Programme. One author reported receiving a CIMED project grant 2024-2026 from Region Stockholm and participating in Midsize Market EACS Ad Board, Warzaw 2023.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.