Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks

COVID-19 Genomics Belgium Consortium, Lize Cuypers, Els Keyaerts, Samuel Leandro Hong, Sarah Gorissen, Soraya Maria Menezes, Marick Starick, Jan Van Elslande, Matthias Weemaes, Tony Wawina-Bokalanga, Joan Marti-Carreras, Bert Vanmechelen, Bram Van Holm, Mandy Bloemen, Jean-Michel Dogne, François Dufrasne, Keith Durkin, Jean Ruelle, Ricardo De Mendonca, Elke WollantsPieter Vermeersch, Caroline Boulouffe, Achille Djiena, Caroline Broucke, Boudewijn Catry, Katrien Lagrou, Marc Van Ranst, Johan Neyts, Guy Baele, Piet Maes, Emmanuel André, Simon Dellicour, Johan Van Weyenbergh

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Coronavirus Disease 2019 (COVID-19) vaccination has resulted in excellent protection against fatal disease, including in older adults. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases among residents) by combining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosol monitoring, whole-genome phylogenetic analysis and immunovirological profiling of nasal mucosa by digital nCounter transcriptomics. Phylogenetic investigations indicated that each outbreak stemmed from a single introduction event, although with different variants (Delta, Gamma and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 d after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 transcriptomic and genomic signatures uncovered a unique IRF3 low/IRF7 high immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy, including environmental sampling, immunomonitoring and early antiviral therapy, should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.

Originele taal-2English
Pagina's (van-tot)722-733
Aantal pagina's12
TijdschriftNature aging
Nummer van het tijdschrift6
Vroegere onlinedatum2023
StatusPublished - jun 2023

Bibliografische nota

Funding Information:
We would like to acknowledge the numerous diagnostics laboratories involved in performing the consecutive screenings in the three nursing homes and for sharing detailed RT–qPCR results. Special thanks go to the representatives of the three nursing homes for providing additional and detailed information to make this collaboration fruitful: the (nursing) staff of Nos Tayons in Nivelles (with specific support of P. Gilbert), of Les Cytises nursing home in Braives and of Ter Burg in Zaventem (with special thanks to N. Deblaere, R. Verschueren and K. Boydens). UZ Leuven, as national reference center for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged. J.M.C. was supported by the HONOURs Marie-Sklodowska-Curie training network (grant 721367). This work is also supported by ‘Interne Fondsen KU Leuven/Internal Funds KU Leuven’ project 3M170314 and C3/20/105 awarded to P.M. The sequencing capacity of this work was supported, in part, by a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N) awarded to P.M., G.B. and E.A. S.D. is supported by the ‘Fonds National de la Recherche Scientifique’ (FNRS, Belgium) and by the European Union Horizon 2020 project MOOD (grant agreement no. 874850). G.B. acknowledges support from the Internal Funds KU Leuven (grant C14/18/094) and from the Research Foundation–Flanders (‘Fonds voor Wetenschappelijk Onderzoek–Vlaanderen’, G0E1420N and G098321N), the latter grant also for S.D. J.V.W. is supported by the Research Foundation–Flanders (G0A0621N and G065421N). P.V. is a senior clinical investigator of the Research Foundation–Flanders. K.K.A. is supported by Research Foundation–Flanders (FWO G0G4220N). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Publisher Copyright:
© 2023, The Author(s).

Copyright 2023 Elsevier B.V., All rights reserved.


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