Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks
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Published:2023-05-22
Issue:6
Volume:3
Page:722-733
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ISSN:2662-8465
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Container-title:Nature Aging
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language:en
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Short-container-title:Nat Aging
Author:
Cuypers Lize, Keyaerts Els, Hong Samuel LeandroORCID, Gorissen Sarah, Menezes Soraya Maria, Starick Marick, Van Elslande Jan, Weemaes Matthias, Wawina-Bokalanga Tony, Marti-Carreras Joan, Vanmechelen Bert, Van Holm BramORCID, Bloemen MandyORCID, Dogne Jean-Michel, Dufrasne FrançoisORCID, Durkin Keith, Ruelle Jean, De Mendonca Ricardo, Wollants Elke, Vermeersch Pieter, Wattiez Ruddy, Peeters Michael, Bakelants Kate, Denayer Sarah, Dufrasne François E., Meex Cécile, Gillet Laurent, Artesi Maria, Hayette Marie-Pierre, Bontems Sébastien, Bours Vincent, Gourzonès Claire, Ek Olivier, Bureau Fabrice, Kabamba Benoit, Gala Jean-Luc, Bearzatto Bertrand, Ambroise Jérôme, Marchant Arnaud, Henin Coralie, Haerlingen Benoit, de Mendonca Ricardo, Delforge Marie-Luce, Vael Carl, Berckmans Lynsey, Selhorst Philippe, Ariën Kevin K., Van Dooren Sonia, Hinckel Bruno, Imamura Hideo, Janssen Toon, Caljon Ben, Soetens Oriane, Piérard Denis, Demuyser Thomas, Michel Charlotte, Vandenberg Olivier, van den Wijngaert Sigi, Zorzi Giulia, Van Lint Philippe, Verstrepen Walter, Naesens Reinout, Van Lent Sarah, Hilbert Pascale, Brohée Sylvain, Léonard Pierre-Emmanuel, Karadurmus Deniz, Gras Jeremie, Féret Damien, Lambert Barbara, Vankeerberghen Anne, Holderbeke Astrid, De Beenhouwer Hans, Cattoir Lien, Lammens Christine, Xavier Basil Britto, Le Mercier Marie, Coppens Jasmine, Matheeussen Veerle, Goossens Herman, Martens Geert A., Swaerts Koen, Van Hoecke Frederik, Desmet Dieter, Descheemaeker Patrick, Bogaerts Pierre, Degosserie Jonathan, Denis Olivier, Huang Te-Din, Obbels Dagmar, Valgaeren Hanne, Frans Johan, Smismans Annick, Claus Paul-Emile, Veltman Denise, Goegebuer Truus, Lemmens Ann, Van den Poel Bea, De Bock Sonja, Laffut Wim, Van Even Ellen, Van Acker Jos, Verfaillie Charlotte, Vanlaere Elke, De Rauw Klara, Waumans Luc, Van Meensel Britt, Cartuyvels Reinoud, Raymaekers Marijke, Verhasselt Bruno, Hellemans Jorn, Vanhee Merijn, Reynders Marijke, Boulouffe Caroline, Djiena Achille, Broucke Caroline, Catry Boudewijn, Lagrou Katrien, Van Ranst Marc, Neyts Johan, Baele Guy, Maes Piet, André Emmanuel, Dellicour Simon, Van Weyenbergh JohanORCID,
Abstract
AbstractCoronavirus 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.
Funder
Fonds Wetenschappelijk Onderzoek KU Leuven Fonds De La Recherche Scientifique - FNRS
Publisher
Springer Science and Business Media LLC
Subject
Neuroscience (miscellaneous),Geriatrics and Gerontology,Aging
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