Post-acute sequelae of hospitalised COVID-19 re-infection compared with hospitalised first-time infection: a population-based retrospective cohort study in Hong Kong.

Introduction: COVID-19 infection is associated with post-acute adverse outcomes affecting multiple organ systems. Although preliminary studies have suggested that COVID-19 re-infection may have a cumulative effect on long-term outcome, differential effects of COVID-19 re-infection severe enough to be hospitalised on post-acute sequelae compared with hospitalised first-time infection have not been explored. Methods: Retrospective cohort study using territory-wide electronic medical records databases in Hong Kong. Adults hospitalised with COVID-19 between 1 January and 30 November 2022, who survived the first 28 days after infection and was discharged, were categorised into re-infection and first-time infection groups. Individuals with reinfection were compared with those with first-time infection for all-cause mortality, all-cause hospital readmission, attendance to the emergency department and complications during the post-acute period using propensity-score-weighted Cox regression. Subgroup analyses were conducted by age (<65 and ≥65 years), sex, Charlson Comorbidity Index (0-4, ≥5), COVID-19 vaccination (0-1, 2+doses) and hospitalisation status of previous infection. Results: 2244 patients with hospitalised COVID-19 re-infection and 58 894 patients with hospitalised first-time COVID-19 infection were included. After a median follow-up of 170 days, re-infection was associated with a significantly higher risk of post-acute all-cause mortality compared with first-time infection (adjusted HR (95% CI): 1.366 (1.166 to 1.600); incidence rate (95% CI): 7.3 (7.1 to 7.5) vs 4.6 (4.4 to 4.7) per 10 000 person-days), all-cause hospital readmission (1.297 (1.200 to 1.403); 50.5 (49.8 to 51.1) vs 28.1 (27.8 to 28.5)), and attendance to emergency departments (1.307 (1.199 to 1.425); 35.4 (34.8 to 35.9) vs 21.9 (21.6 to 22.2)). Findings were consistent across subgroups of age, sex, health status and vaccination status. A greater magnitude of increased risk was observed especially among those hospitalised during a previous infection. Conclusion: Among patients with COVID-19 infection requiring hospitalisation, COVID-19 re-infection was associated with increased post-acute mortality and morbidity compared with first-time infection. Further studies are warranted to delineate the effects on complications.