Post COVID-19 condition after Wildtype, Delta, and Omicron variant SARS-CoV-2 infection and vaccination: pooled analysis of two population-based cohorts

Abstract

Background: Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. Further evidence is needed on the risk of PCC after vaccination and infection with newer variants. This study aimed to evaluate the prevalence and severity of PCC across different variants and vaccination histories. Methods: We used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses. Findings: We found strong evidence that vaccinated individuals infected with Omicron had a reduced risk of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The risk among non-vaccinated individuals was similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants. Interpretation: The risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies. Study registrations: ISRCTN14990068, ISRCTN18181860

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study is part of the Corona Immunitas research network, coordinated by the Swiss School of Public Health (SSPH+), and funded by fundraising of SSPH+ including funds of the Swiss Federal Office of Public Health and private funders (ethical guidelines for funding stated by SSPH+ were respected), by funds of the cantons of Switzerland (Vaud, Zurich, and Basel), and by institutional funds of the Universities. Additional funding specific for the two cohorts included in this study was received from the Department of Health of the canton of Zurich, the University of Zurich (UZH) Foundation, and the Swiss Federal Office of Public Health. TB received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801076, through the SSPH+ Global PhD Fellowship Programme in Public Health Sciences (GlobalP3HS) of the SSPH+. DM received funding by the UZH Postdoc Grant, grant no. FK-22-053.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics committee of the canton of Zurich, Switzerland, gave ethical approval for the Zurich SARS-CoV-2 Cohort study (BASEC 2020-01739). The ethics committees of the cantons of Zurich and Ticino, Switzerland, gave ethical approval for the Corona Immunitas study (BASEC 2020-01247 and BASEC 2020-01514, respectively).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

Deidentified individual participant data underlying the findings of this study will be available for researchers submitting a methodologically sound proposal to achieve the aims of the proposal after peer-reviewed publication of this article.

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