Association Between COVID-19 Vaccination and Long COVID Symptoms in Hospitalised Survivors: Distinguishing Prevention from Reverse Causality

<b>Background</b>: While COVID-19 vaccination significantly reduces acute disease severity, its impact on the incidence of long COVID remains debated, with some observational studies paradoxically suggesting higher symptom rates among vaccinated individuals. This study aimed to resolve this controversy by distinguishing between the protective effects of prior immunity and the confounding influence of reverse causality. <b>Methods</b>: We conducted a retrospective cohort study of 627 adults hospitalised for COVID-19 in London. Participants were stratified into two analytical cohorts based on vaccination timing: a "prevention cohort" (vaccinated ≥14 days pre-infection) and a "post-acute cohort" (vaccinated post-infection). Multivariable Bayesian logistic regression was employed to estimate Adjusted Odds Ratios (aOR) for long COVID, controlling for age, gender, BMI, comorbidities, and acute length of hospital stay (LoS). <b>Results</b>: In the prevention cohort, prior vaccination demonstrated a non-significant protective trend against long COVID (aOR 0.81; 95% CI 0.45-1.42; <i>p</i> = 0.45), with no significant difference observed between homologous and heterologous regimens. The post-acute cohort exhibited a strong, significant positive association (aOR 3.41; 95% CI 2.23-5.52; <i>p</i> < 0.001), indicating substantial indication bias, with symptomatic individuals more likely to seek vaccination. The strongest independent predictors of long COVID were comorbidities (aOR 2.78) and prolonged acute hospitalisation (≥4 days; aOR 1.82). <b>Conclusions</b>: Vaccination administered prior to infection demonstrates a protective trend against long COVID, whereas the strong association observed with post-infection vaccination reflects indication bias, with symptomatic survivors being more likely to seek immunisation. Clinical strategies to mitigate post-acute sequelae should prioritise reducing acute disease severity and managing comorbidities, which were identified as the dominant independent predictors of risk in hospitalised patients.

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Publication Details

Journal
Biomedicines
Published
2026-02-02
DOI
https://doi.org/10.3390/biomedicines14020350
Primary Topic
Long-Term Effects of COVID-19
Type
article
Field-Weighted Citation Impact
0.00

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article

Association Between COVID-19 Vaccination and Long COVID Symptoms in Hospitalised Survivors: Distinguishing Prevention from Reverse Causality

Judith Allgrove, Lanre Peter Daodu, Francesca I. F. Arrigoni, Reem Kayyali et al.
Biomedicines
Long-Term Effects of COVID-19
article

Association Between COVID-19 Vaccination and Long COVID Symptoms in Hospitalised Survivors: Distinguishing Prevention from Reverse Causality

Judith Allgrove, Lanre Peter Daodu, Francesca I. F. Arrigoni, Reem Kayyali, Yogini Raste
article en

Abstract

<b>Background</b>: While COVID-19 vaccination significantly reduces acute disease severity, its impact on the incidence of long COVID remains debated, with some observational studies paradoxically suggesting higher symptom rates among vaccinated individuals. This study aimed to resolve this controversy by distinguishing between the protective effects of prior immunity and the confounding influence of reverse causality. <b>Methods</b>: We conducted a retrospective cohort study of 627 adults hospitalised for COVID-19 in London. Participants were stratified into two analytical cohorts based on vaccination timing: a "prevention cohort" (vaccinated ≥14 days pre-infection) and a "post-acute cohort" (vaccinated post-infection). Multivariable Bayesian logistic regression was employed to estimate Adjusted Odds Ratios (aOR) for long COVID, controlling for age, gender, BMI, comorbidities, and acute length of hospital stay (LoS). <b>Results</b>: In the prevention cohort, prior vaccination demonstrated a non-significant protective trend against long COVID (aOR 0.81; 95% CI 0.45-1.42; <i>p</i> = 0.45), with no significant difference observed between homologous and heterologous regimens. The post-acute cohort exhibited a strong, significant positive association (aOR 3.41; 95% CI 2.23-5.52; <i>p</i> < 0.001), indicating substantial indication bias, with symptomatic individuals more likely to seek vaccination. The strongest independent predictors of long COVID were comorbidities (aOR 2.78) and prolonged acute hospitalisation (≥4 days; aOR 1.82). <b>Conclusions</b>: Vaccination administered prior to infection demonstrates a protective trend against long COVID, whereas the strong association observed with post-infection vaccination reflects indication bias, with symptomatic survivors being more likely to seek immunisation. Clinical strategies to mitigate post-acute sequelae should prioritise reducing acute disease severity and managing comorbidities, which were identified as the dominant independent predictors of risk in hospitalised patients.

BiomedicinesVol. 14(2)
Kingston University London (GB), Croydon University Hospital (GB), Croydon Health Services NHS Trust (GB), Bournemouth University (GB)
Health and Care Research Wales
Good health and well-being
Openalex Percentile: Top 70%
Long-Term Effects of COVID-19
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