Association of nirmatrelvir-ritonavir with post-acute sequelae and mortality among patients who are immunocompromised with COVID-19 in Hong Kong: a retrospective cohort study.

Background: The effect of nirmatrelvir-ritonavir on post-COVID-19 outcomes for individuals who are immunocompromised is understudied. We aimed to examine the association of nirmatrelvir-ritonavir with post-acute sequelae and mortality among patients who are immunocompromised and admitted to hospital with COVID-19.

Methods: We did a retrospective cohort study using territory-wide electronic health records from the Hong Kong Hospital Authority and Hong Kong Department of Health. Eligible patients were adults aged 18 years or older who tested positive for SARS-CoV-2 during the study period (March 11, 2022, to Nov 9, 2023) and were admitted to hospital with COVID-19. Four exposure groups were formed based on immune status (immunocompromised or immunocompetent) and nirmatrelvir-ritonavir status (yes or no). The primary outcome was post-acute inpatient death, starting from 21 days after the positive RT-PCR date. Standardised mortality ratio weighting with doubly robust adjustment was applied to control for confounders. Cox models were used to estimate hazard ratios (HRs) for the outcomes.

Findings: Between March 11, 2022, and Nov 9, 2023, there were 89 772 individuals with positive RT-PCR tests, of whom 39 923 met eligibility criteria and were included in the study cohort. 19 914 (49·9%) of 39 923 patients were female, 20 009 (50·1%) were male and the median age was 75·0 years (IQR 63·0-85·0). 846 (38·2%) of 2217 patients who were immunocompromised and 14 586 (38·7%) of 37 706 patients who were immunocompetent were prescribed nirmatrelvir-ritonavir. Among the patients who were immunocompromised, those patients who received nirmatrelvir-ritonavir had significantly lower risk of post-acute inpatient death (HR 0·58, 95% CI 0·45-0·74; p<0·0001) and hospitalisation for acute respiratory distress syndrome (0·43, 0·20-0·90; p=0·024) than those who did not. A significant negative interaction was found between immune status and nirmatrelvir-ritonavir on post-acute all-cause hospitalisation (relative excess risk due to interaction -0·84, 95% CI -1·30 to -0·37; p=0·0004).

Interpretation: Nirmatrelvir-ritonavir was associated with reduced risk of post-acute inpatient death among patients who were immunocompromised and admitted to hospital with COVID-19. However, the effectiveness of nirmatrelvir-ritonavir on post-acute hospitalisation outcomes was less pronounced in patients who were immunocompromised than in patients who were immunocompetent.

Funding: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.