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

Guozhang Lin; Yuchen Wei; Huwen Wang; Christopher Boyer; Katherine Min Jia; Chi Tim Hung; Xiaoting Jiang; Conglu Li; Carrie Ho Kwan Yam; Tsz Yu Chow; Yawen Wang; Shi Zhao; Zihao Guo; Kehang Li; Aimin Yang; Chris Ka Pun Mok; David S C Hui; Ka Chun Chong; Eng Kiong Yeoh

doi:10.1016/S2665-9913(24)00224-8

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

Lancet Rheumatol. 2024 Nov 8:S2665-9913(24)00224-8. doi: 10.1016/S2665-9913(24)00224-8. Online ahead of print.

Authors

Guozhang Lin¹, Yuchen Wei¹, Huwen Wang¹, Christopher Boyer², Katherine Min Jia², Chi Tim Hung¹, Xiaoting Jiang¹, Conglu Li¹, Carrie Ho Kwan Yam¹, Tsz Yu Chow¹, Yawen Wang³, Shi Zhao⁴, Zihao Guo¹, Kehang Li¹, Aimin Yang⁵, Chris Ka Pun Mok⁶, David S C Hui⁷, Ka Chun Chong⁸, Eng Kiong Yeoh¹

Affiliations

¹ School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China.
² Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
³ Division of Landscape Architecture, Department of Architecture, Faculty of Architecture, The University of Hong Kong, Hong Kong, China.
⁴ School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China; School of Public Health, Tianjin Medical University, Tianjin, China.
⁵ Department of Medicine & Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
⁶ Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
⁷ SH Ho Research Centre for Infectious Diseases, Chinese University of Hong Kong, Hong Kong, China.
⁸ School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China. Electronic address: marc@cuhk.edu.hk.

PMID: 39527967
DOI: 10.1016/S2665-9913(24)00224-8

Abstract

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.