Effectiveness of oseltamivir in hospitalised obstetric patients with COVID-19: a retrospective cohort study using a Brazilian national database

Effective, safe, and accessible antivirals are needed to treat pregnant/postpartum (obstetric) patients with COVID-19, a group at high risk for severe disease. Newer antivirals (nirmatrelvir/ritonavir, remdesivir) are expensive and less accessible in low- and middle-income countries, including Brazil. Oseltamivir, a cheap, widely available, pregnancy-safe anti-influenza medication, was used off-label for COVID-19 in Brazil. The primary outcome was comparing in-hospital all-cause mortality in hospitalised obstetric patients with COVID-19 treated with oseltamivir versus no antivirals. Secondary outcomes were comparing the risk of progression to severe disease (ICU admission or death, whichever occurred first) and hospital discharge. In this retrospective matched cohort study using Brazil’s national surveillance database (SIVEP-Gripe), we identified hospitalised obstetric patients with PCR-confirmed COVID-19 between February 2020 and October 2023. Patients first receiving oseltamivir on day zero of admission and admitted within seven days of symptom onset were matched 1:1 using propensity scores to patients receiving no antivirals at all. After matching, 445 oseltamivir recipients and 445 controls were included, of whom 79.5% and 80.0%, respectively, were admitted in 2020, and 65.8% and 67.9% had non-severe COVID-19 on admission (SpO2 > 94%). Oseltamivir use was associated with a lower risk of in-hospital death (hazard ratio [HR] 0.77; [95% CI 0.51–1.17], p = 0.22; absolute risk reduction [ARR] 3.9%) and progression to severe disease (HR 0.83 [95% CI [0.67–1.01], p = 0.07; ARR 4.5%) compared with no antivirals, though these associations were not statistically significant overall. Oseltamivir recipients were less likely to be discharged on days 0–2 (HR 0.68 [0.52–0.90]) but more likely to be discharged on or after day 3 (HR 1.30 [1.10–1.54]) than controls. Significant associations between oseltamivir use and lower in-hospital mortality were observed in two subgroups: patients admitted in 2020 (HR 0.54 [95% CI 0.32–0.93], p = 0.03) and patients with non-severe COVID-19 (SpO2 > 94%) on admission (HR 0.33 [95% CI 0.12–0.89], p = 0.03). In obstetric patients with COVID-19, oseltamivir used within seven days of symptom onset was associated with non-statistically significant lower risk of in-hospital death and progression to severe disease, compared with no antivirals. Results of this study do not support use of oseltamivir to treat COVID-19 in this population.