Association between COVID-19 vaccination, SARS-CoV-2 variants, and post COVID-19 condition: A cross-sectional study
Saif-El-Din El-Akkad, Selena Shao, Karen C. Tran, Hiten Naik, Naveed Janjua, Hind Sbihi, Christopher Carlsten, James A. Russell, Adeera Levin, Alyson W. Wong
Abstract
Background
Individuals may experience persistent symptoms after recovering from coronavirus disease 2019 (COVID-19), a condition referred to as post COVID-19 condition (PCC). Patient-reported outcome measures (PROMs) evaluate a patient’s health status and can be used to quantify symptom severity from the patient’s perspective. The impact of COVID-19 vaccination and variant of infection on PCC is not well understood. We therefore sought to explore vaccination and variant trends among individuals with PCC and investigate their association with abnormal PROMs.
Introduction
Persistent symptoms following Coronavirus Disease 2019 (COVID-19) is common and is referred to as post COVID-19 condition (PCC) [1]. A meta-analysis of 194 studies and 735,000 patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), who had varying severities of acute illness, found that 45% of patients met diagnostic criteria for PCC [2]. A better understanding of how certain SARS-CoV-2 variants and vaccination status relate to PCC symptoms is needed to inform preventative measures and treatments.
Methods
Study population
We studied a longitudinal cohort of patients seen in one of four Post-COVID-19 recovery clinics (PCRCs) in British Columbia, Canada between March 2020 and October 2022. The data was accessed for research purposes between 25-05-2022 and 19-06-2024. The PCRC consists of a multidisciplinary healthcare team that includes physicians, nurses, and other allied health professionals [9].
Results
Patient characteristics
There were 1587 participants included in the study (Fig 1): 1481 (93%) participants had a confirmed positive SARS-CoV-2 PCR test, while 106 (7%) participants had a confirmed SARS-CoV-2 infection date but no documented PCR test upon referral to the PCRC. The mean age for the total cohort was 52 years and similar between the vaccination groups (Table 1).
Discussion
This study aimed to explore the association between 1) COVID-19 vaccination status and 2) SARS-CoV-2 variants and the presence of PCC symptoms (fatigue, dyspnea, anxiety, depression, PTSD) using PROMs. In the adjusted analyses, non-hospitalized patients who were fully vaccinated prior to their COVID-19 illness were less likely to report PTSD symptoms compared to unvaccinated patients; while hospitalized patients infected with alpha or gamma variants were more likely to report dyspnea and less likely depression, respectively, compared to those infected with the wildtype strain.
Conclusion
Patients who were partially or fully vaccinated did not have increased risk of common PCC symptoms. Infection with the alpha and delta variants was associated with increased likelihood of reporting dyspnea, which may be related to the severity of acute illness and associated impairments in lung function. Further studies on whether different biologic mechanisms could explain the heterogeneity of PCC symptoms between the SARS-CoV-2 variants are need.
Citation: El-Akkad S-E-D, Shao S, Tran KC, Naik H, Janjua N, Sbihi H, et al. (2025) Association between COVID-19 vaccination, SARS-CoV-2 variants, and post COVID-19 condition: A cross-sectional study. PLoS One 20(12): e0336929. https://doi.org/10.1371/journal.pone.0336929
Editor: Dong Keon Yon, Kyung Hee University College of Medicine, KOREA, REPUBLIC OF
Received: February 19, 2025; Accepted: October 31, 2025; Published: December 2, 2025
Copyright: © 2025 El-Akkad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: According to the University of British Columbia Clinical Research Ethics Board (UBC CREB), we are prohibited from sharing data publicly as there is potentially sensitive information. Data requests may be sent to the UBC CREB at the following address: Room 210, Research Pavilion - 828 West 10th Ave, Vancouver, BC Canada V5Z1M9.
Funding: AWW received funding from the Canadian Lung Association (CLA) / Canadian Institutes of Health Research (CIHR) Respiratory Health Effects of PCC Grant (Funding reference 181075). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
