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, Carol Strahm, Sabine Güsewell, Alexia Cusini, Angela Brucher, Stephan Goppel, Elisabeth Möller, Jens Carsten Möller, Manuela Ortner, Markus Ruetti, Reto Stocker, Danielle Vuichard‐Gysin, Ulrike Besold, Allison McGeer, Lorenz Risch, Andrée Friedl, Matthias Schlegel, Pietro Vernazza, Stefan P. Kuster, Philipp Köhler, for the SURPRISE (SURveillance of infectious diseases among health PRofessionals In SwitzErland) Study Group, Ulrike Besold, Angela Brucher, Alexia Cusini, Thomas Egger, Andrée Friedl, Stephan Goppel, Fabian Grässli, Christian R. Kahlert, Joelle Keller, Simone Kessler, Philipp Kohler, Stefan P. Kuster, Onício Leal Neto, Eva Lemmenmeier, Allison McGeer, Dorette Meier Kleeb, Elisabeth Möller, Jens Carsten Möller, Maja Müller, Vaxhid Musa, Manuela Ortner, Philip Rieder, Lorenz Risch, Markus Ruetti, Matthias Schlegel, Hans-Ruedi Schmid, Reto Stocker, Pietro Vernazza, Matthias von Kietzell, Danielle Vuichard-Gysin, Benedikt Wiggli
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.