SARS-CoV-2 rebound and post-acute mortality and hospitalization among patients admitted with COVID-19: cohort study

Ka Chun Chong, Yuchen Wei, Katherine Min Jia, Christopher Boyer, Guozhang Lin, Huwen Wang, Conglu Li, Chi Tim Hung, Xiaoting Jiang, Carrie Ho Kwan Yam, Tsz Yu Chow, Yawen Wang, Shi Zhao, Kehang Li, Aimin Yang, Chris Ka Pun Mok, David SC Hui, Eng Kiong Yeoh () and Zihao Guo ()
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Ka Chun Chong: The Chinese University of Hong Kong
Yuchen Wei: The Chinese University of Hong Kong
Katherine Min Jia: Harvard T.H. Chan School of Public Health
Christopher Boyer: Harvard T.H. Chan School of Public Health
Guozhang Lin: The Chinese University of Hong Kong
Huwen Wang: The Chinese University of Hong Kong
Conglu Li: The Chinese University of Hong Kong
Chi Tim Hung: The Chinese University of Hong Kong
Xiaoting Jiang: The Chinese University of Hong Kong
Carrie Ho Kwan Yam: The Chinese University of Hong Kong
Tsz Yu Chow: The Chinese University of Hong Kong
Yawen Wang: The University of Hong Kong
Shi Zhao: The Chinese University of Hong Kong
Kehang Li: The Chinese University of Hong Kong
Aimin Yang: The Chinese University of Hong Kong
Chris Ka Pun Mok: Chinese University of Hong Kong
David SC Hui: Chinese University of Hong Kong
Eng Kiong Yeoh: The Chinese University of Hong Kong
Zihao Guo: The Chinese University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions. Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong. Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group, respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36–1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41–2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18–1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID.

Date: 2025
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DOI: 10.1038/s41467-025-61737-7

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