[en] 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.
Disciplines :
Microbiology
Author, co-author :
Cuypers, Lize; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium
Keyaerts, Els; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium
Hong, Samuel Leandro ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Gorissen, Sarah; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium
Menezes, Soraya Maria; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Starick, Marick; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Van Elslande, Jan; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium
Weemaes, Matthias; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium
Wawina-Bokalanga, Tony; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Marti-Carreras, Joan; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Vanmechelen, Bert; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Van Holm, Bram ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Bloemen, Mandy ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Dogne, Jean-Michel; Department of Pharmacy, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium
Dufrasne, François ; Laboratory of Proteomics and Microbiology, University of Mons, Mons, Belgium ; Department of Infectious Diseases, Laboratory of Viral Diseases, National Institute for Public Health (Sciensano), Brussels, Belgium
Durkin, Keith ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Laboratory of Human Genetics, GIGA Research Institute, Liège, Belgium
Ruelle, Jean; Medical Microbiology Unit (MBLG), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium
De Mendonca, Ricardo; Université Libre de Bruxelles (ULB), Brussels, Belgium
Wollants, Elke; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Vermeersch, Pieter; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium
COVID-19 Genomics Belgium Consortium
Boulouffe, Caroline; Infectious Disease Surveillance Unit, Agence pour une vie de qualité (AVIQ), Wallonia, Belgium
Djiena, Achille; Infectious Disease Surveillance Unit, Agence pour une vie de qualité (AVIQ), Wallonia, Belgium
Catry, Boudewijn; Unit Healthcare-Associated Infections and Antimicrobial Resistance, Sciensano, Brussels, Belgium
Lagrou, Katrien; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium
Van Ranst, Marc; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Neyts, Johan; Department of Microbiology, Immunology and Transplantation, Laboratory Virology and Chemotherapy, Rega Institute, KU Leuven, Leuven, Belgium
Baele, Guy; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
Maes, Piet; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium
André, Emmanuel; Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium
Dellicour, Simon; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium ; Spatial Epidemiology Lab (SpELL), Université Libre de Bruxelles, Bruxelles, Belgium
Van Weyenbergh, Johan ; Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, Belgium. johan.vanweyenbergh@kuleuven.be
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE] KU Leuven - Catholic University of Leuven [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
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.
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