Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2023 Jul 26;77(2):194-202.
doi: 10.1093/cid/ciad143.

Post-Acute Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Viral Variant and Vaccination Status: A Multicenter Cross-Sectional Study

Christian R Kahlert  1   2 , Carol Strahm  1 , Sabine Güsewell  1 , Alexia Cusini  3 , Angela Brucher  4 , Stephan Goppel  5 , Elisabeth Möller  6 , J Carsten Möller  7 , Manuela Ortner  8 , Markus Ruetti  9 , Reto Stocker  10 , Danielle Vuichard-Gysin  11   12 , Ulrike Besold  13 , Allison McGeer  14 , Lorenz Risch  15   16   17 , Andrée Friedl  18 , Matthias Schlegel  1 , Pietro Vernazza  1 , Stefan P Kuster  1 , Philipp Kohler  1 ; SURPRISE (SURveillance of infectious diseases among health PRofessionals In SwitzErland) Study Group
Collaborators, Affiliations
Multicenter Study

Post-Acute Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Viral Variant and Vaccination Status: A Multicenter Cross-Sectional Study

Christian R Kahlert et al. Clin Infect Dis. .

Abstract

Background: Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC.

Methods: We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status.

Results: Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1-2 vaccinations (P = .028) and 0.49 with ≥3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08-3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10-3.46) were significantly associated with the outcome.

Conclusions: Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.

Keywords: healthcare workers; long COVID; post-acute sequelae of SARS-CoV-2; vaccination; viral variant.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. A. M. has received grant funding outside of the current work from Pfizer, SanofiPasteur, and Merck (paid to their institution); consulting fees from Sienna Senior Living (paid to the author); as well as honoraria for advisory boards, webinars, and/or Data and Safety Monitoring Board (DSMB) membership for AstraZeneca, Biogen, GlaxoSmithKline, Janssen, Medicago, Merck, Moderna, Novavax, Pfizer, and SanofiPasteur. A. M. also received travel support from Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/post-acute-sequelae-after-sars-cov-2-infection-by-viral-variant-and-vaccination-status-a-multicenter-cross-sectional-study
Figure 1.
Figure 1.
A–C, Cross-sectional analysis of May/June 2022. Means and 95% confidence intervals of post-acute sequelae of SARS-CoV-2 symptom score by vaccination status and viral variant dominating at the time of infection. Asterisks above the bars indicate statistical significance in reference to uninfected participants with the same vaccination status, respectively, as obtained through Wald tests on coefficients of negative binomial models with uninfected participants as the reference group: ***P < .001; **P < .01; *P < .05; nsP ≥ .05. The numbers at the bottom of the bars designate the number of participants. Note: there were no vaccinations before wild-type infection and only 3 individuals were vaccinated after Omicron BA.1 infection (not shown in panel C). Abbreviations: ns, not significant; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 2.
Figure 2.
Means and 95% confidence intervals of post-acute sequelae of SARS-CoV-2 symptom score in relation to number of vaccine doses received before positive swab. Left: Participants after infection in the Delta period (1 July to 31 December 2021). Right: Participants after infection in the Omicron BA.1 period (1 January to 30 June 2022). The asterisk above the bar indicates statistical significance in reference to unvaccinated participants infected in the same period, respectively, as obtained through Wald tests on coefficients of negative binomial models with group “none” as the reference: *P < .05; nsP ≥ .05. Abbreviations: ns, not significant; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 3.
Figure 3.
Results of a multivariable negative binomial model regarding number of symptoms compatible with post-acute sequelae of SARS-CoV-2. For numeric values of point estimates and 95% confidence intervals, see Supplementary Table 4. Abbreviations: BMI, body mass index; COVID-19, coronavirus disease 2019; FTE, full-time equivalent; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Phillips S, Williams MA. Confronting our next national health disaster—long-haul Covid. N Engl J Med 2021; 385:577–9. - PubMed
    1. Nasserie T, Hittle M, Goodman SN. Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw Open 2021; 4:e2111417. - PMC - PubMed
    1. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis 2022; 226:1593–607. - PMC - PubMed
    1. Global Burden of Disease Long COVID Collaborators . Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA 2022; 328: 1604–15. - PMC - PubMed
    1. Peter RS, Nieters A, Kräusslich H-G, et al. . Post-acute sequelae of COVID-19 six to 12 months after infection: population based study. BMJ 2022; 379:e071050. - PMC - PubMed

Publication types

Supplementary concepts