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

K Ka Chun Chong Y Yuchen Wei K Katherine Min Jia C Christopher Boyer G Guozhang Lin H Huwen Wang C Conglu Li C Chi Tim Hung X Xiaoting Jiang C Carrie Ho Kwan Yam T Tsz Yu Chow Y Yawen Wang S Shi Zhao K Kehang Li A Aimin Yang C Chris Ka Pun Mok D David SC Hui E Eng Kiong Yeoh Z Zihao Guo (State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Frontier Interdisciplinary Science Research Center, School of Chemistry and Chemical Engineering)

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published July 28, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (19)

K

Ka Chun Chong

Y

Yuchen Wei

K

Katherine Min Jia

C

Christopher Boyer

G

Guozhang Lin

H

Huwen Wang

C

Conglu Li

C

Chi Tim Hung

X

Xiaoting Jiang

C

Carrie Ho Kwan Yam

T

Tsz Yu Chow

Y

Yawen Wang

S

Shi Zhao

K

Kehang Li

A

Aimin Yang

C

Chris Ka Pun Mok

D

David SC Hui

E

Eng Kiong Yeoh

Z

Zihao Guo

State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Frontier Interdisciplinary Science Research Center, School of Chemistry and Chemical Engineering