Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study

Boyan Liu; Song Song; Wenlong Liu; Yuqi Hu; Cuiling Wei; Lingyue Zhou; Qi Sun; Wenxin Tian; Rachel Yui Ki Chu; Ian Chi Kei Wong; Ivan Fan Ngai Hung; Eric Yuk Fai Wan; Xue Li; Celine Sze Ling Chui; Esther Wai Yin Chan; Carlos King Ho Wong; Francisco Tsz Tsun Lai

doi:10.1016/j.jinf.2025.106597

Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study

Boyan Liu
, Song Song^*
, Wenlong Liu
, Yuqi Hu
, Cuiling Wei
, Lingyue Zhou
, Qi Sun
, Wenxin Tian
, Rachel Yui Ki Chu
, Ian Chi Kei Wong
, Ivan Fan Ngai Hung
, Eric Yuk Fai Wan
, Xue Li
, Celine Sze Ling Chui
, Esther Wai Yin Chan
, Carlos King Ho Wong
, Francisco Tsz Tsun Lai^*

^*Corresponding author for this work

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Laboratory of Data Discovery for Health
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
The University of Hong Kong, Shenzhen Institute of Research and Innovation, Shenzhen, China.
Department of Infectious Disease Epidemiology and Dynamics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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Abstract

Background: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. Methods: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. Results: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96–313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18–69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85–88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27–74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23–1.29) for unvaccinated and 1.08 (95% CI: 1.05–1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. Interpretation: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.

Original language	English
Article number	106597
Number of pages	8
Journal	Journal of Infection
Volume	91
Issue number	3
Early online date	21 Aug 2025
DOIs	https://doi.org/10.1016/j.jinf.2025.106597
Publication status	Published - Sept 2025

Bibliographical note

Copyright © 2025 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Funding

This study received support from the Health Bureau, The Government of the Hong Kong Special Administrative Region through the Health and Medical Research Fund (Ref. No. COVID19F01 and 22211202) and the Collaborative Research Fund, University Grants Committee, The Government of the Hong Kong Special Administrative Region (Ref. No. C7154-20GF). F.T.T.L., C.K.H.W., and I.C.K.W.’s post received partial funding from D24H. Hence, this work was also partially supported by InnoHK initiative of the Innovation and Technology Commission of the Hong Kong Special Administrative Region Government.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

COVID-19
Long-COVID
Multimorbidity
Primary health care
Public health
Vaccination

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10.1016/j.jinf.2025.106597Licence: CC BY 4.0

Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity
Copyright © 2025 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
Final published version, 3.67 MBLicence: CC BY 4.0

Cite this

Liu, B., Song, S., Liu, W., Hu, Y., Wei, C., Zhou, L., Sun, Q., Tian, W., Chu, R. Y. K., Wong, I. C. K., Hung, I. F. N., Wan, E. Y. F., Li, X., Chui, C. S. L., Chan, E. W. Y., Wong, C. K. H., & Lai, F. T. T. (2025). Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study. Journal of Infection, 91(3), Article 106597. https://doi.org/10.1016/j.jinf.2025.106597

@article{5277807d637e4a81a2c30b23c650566d,

title = "Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study",

abstract = "Background: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. Methods: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. Results: Among 1,038,175 eligible individuals, 68,975 (6.64\%) developed multimorbidity over a median follow-up of 192 days (IQR: 96–313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95\% CI: 68.18–69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95\% CI: 84.85–88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95\% CI: 71.27–74.43). Adjusted incidence rate ratios were 1.26 (95\% CI: 1.23–1.29) for unvaccinated and 1.08 (95\% CI: 1.05–1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. Interpretation: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.",

keywords = "COVID-19, Long-COVID, Multimorbidity, Primary health care, Public health, Vaccination",

author = "Boyan Liu and Song Song and Wenlong Liu and Yuqi Hu and Cuiling Wei and Lingyue Zhou and Qi Sun and Wenxin Tian and Chu, \{Rachel Yui Ki\} and Wong, \{Ian Chi Kei\} and Hung, \{Ivan Fan Ngai\} and Wan, \{Eric Yuk Fai\} and Xue Li and Chui, \{Celine Sze Ling\} and Chan, \{Esther Wai Yin\} and Wong, \{Carlos King Ho\} and Lai, \{Francisco Tsz Tsun\}",

note = "Copyright {\textcopyright} 2025 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/). ",

year = "2025",

month = sep,

doi = "10.1016/j.jinf.2025.106597",

language = "English",

volume = "91",

journal = "Journal of Infection",

issn = "0163-4453",

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Liu, B, Song, S, Liu, W, Hu, Y, Wei, C, Zhou, L, Sun, Q, Tian, W, Chu, RYK, Wong, ICK, Hung, IFN, Wan, EYF, Li, X, Chui, CSL, Chan, EWY, Wong, CKH & Lai, FTT 2025, 'Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study', Journal of Infection, vol. 91, no. 3, 106597. https://doi.org/10.1016/j.jinf.2025.106597

TY - JOUR

T1 - Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study

AU - Liu, Boyan

AU - Song, Song

AU - Liu, Wenlong

AU - Hu, Yuqi

AU - Wei, Cuiling

AU - Zhou, Lingyue

AU - Sun, Qi

AU - Tian, Wenxin

AU - Chu, Rachel Yui Ki

AU - Wong, Ian Chi Kei

AU - Hung, Ivan Fan Ngai

AU - Wan, Eric Yuk Fai

AU - Li, Xue

AU - Chui, Celine Sze Ling

AU - Chan, Esther Wai Yin

AU - Wong, Carlos King Ho

AU - Lai, Francisco Tsz Tsun

N1 - Copyright © 2025 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

PY - 2025/9

Y1 - 2025/9

N2 - Background: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. Methods: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. Results: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96–313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18–69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85–88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27–74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23–1.29) for unvaccinated and 1.08 (95% CI: 1.05–1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. Interpretation: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.

AB - Background: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. Methods: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. Results: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96–313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18–69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85–88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27–74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23–1.29) for unvaccinated and 1.08 (95% CI: 1.05–1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. Interpretation: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.

KW - COVID-19

KW - Long-COVID

KW - Multimorbidity

KW - Primary health care

KW - Public health

KW - Vaccination

UR - https://www.journalofinfection.com/article/S0163-4453(25)00197-5/fulltext

UR - https://www.scopus.com/pages/publications/105013991673

U2 - 10.1016/j.jinf.2025.106597

DO - 10.1016/j.jinf.2025.106597

M3 - Article

SN - 0163-4453

VL - 91

JO - Journal of Infection

JF - Journal of Infection

IS - 3

M1 - 106597

ER -

Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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