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 Wollants; Pieter 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

doi:10.1038/s43587-023-00421-1

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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Abstract

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.

Original language	English
Pages (from-to)	722-733
Number of pages	12
Journal	Nature aging
Volume	3
Issue number	6
Early online date	2023
DOIs	https://doi.org/10.1038/s43587-023-00421-1
Publication status	Published - Jun 2023

Bibliographical note

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

Keywords

Immunovirological screening
environmental screening
COVID-19
post-vaccination
nursing home outbreaks

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COVID-19 Genomics Belgium Consortium, Cuypers, L., Keyaerts, E., Hong, S. L., Gorissen, S., Menezes, S. M., Starick, M., Van Elslande, J., Weemaes, M., Wawina-Bokalanga, T., Marti-Carreras, J., Vanmechelen, B., Van Holm, B., Bloemen, M., Dogne, J-M., Dufrasne, F., Durkin, K., Ruelle, J., De Mendonca, R., ... Van Weyenbergh, J. (2023). Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks. Nature aging, 3(6), 722-733. https://doi.org/10.1038/s43587-023-00421-1

COVID-19 Genomics Belgium Consortium ; Cuypers, Lize ; Keyaerts, Els ; Hong, Samuel Leandro ; Gorissen, Sarah ; Menezes, Soraya Maria ; Starick, Marick ; Van Elslande, Jan ; Weemaes, Matthias ; Wawina-Bokalanga, Tony ; Marti-Carreras, Joan ; Vanmechelen, Bert ; Van Holm, Bram ; Bloemen, Mandy ; Dogne, Jean-Michel ; Dufrasne, François ; Durkin, Keith ; Ruelle, Jean ; De Mendonca, Ricardo ; Wollants, Elke ; Vermeersch, Pieter ; 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, Johan. / Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks. In: Nature aging. 2023 ; Vol. 3, No. 6. pp. 722-733.

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

abstract = "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.",

keywords = "Immunovirological screening, environmental screening, COVID-19, post-vaccination, nursing home outbreaks",

author = "{COVID-19 Genomics Belgium Consortium} and Lize Cuypers and Els Keyaerts and Hong, {Samuel Leandro} and Sarah Gorissen and Menezes, {Soraya Maria} and Marick Starick and {Van Elslande}, Jan and Matthias Weemaes and Tony Wawina-Bokalanga and Joan Marti-Carreras and Bert Vanmechelen and {Van Holm}, Bram and Mandy Bloemen and Jean-Michel Dogne and Fran{\c c}ois Dufrasne and Keith Durkin and Jean Ruelle and {De Mendonca}, Ricardo and Elke Wollants and Pieter Vermeersch and Caroline Boulouffe and Achille Djiena and Caroline Broucke and Boudewijn Catry and Katrien Lagrou and {Van Ranst}, Marc and Johan Neyts and Guy Baele and Piet Maes and Emmanuel Andr{\'e} and Simon Dellicour and {Van Weyenbergh}, Johan and Denis Pierard",

note = "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 {\textquoteleft}Interne Fondsen KU Leuven/Internal Funds KU Leuven{\textquoteright} 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 {\textquoteleft}Fonds Wetenschappelijk Onderzoek{\textquoteright}/Research Foundation Flanders (grant G0H4420N) awarded to P.M., G.B. and E.A. S.D. is supported by the {\textquoteleft}Fonds National de la Recherche Scientifique{\textquoteright} (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 ({\textquoteleft}Fonds voor Wetenschappelijk Onderzoek–Vlaanderen{\textquoteright}, 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: {\textcopyright} 2023, The Author(s). Copyright: Copyright 2023 Elsevier B.V., All rights reserved.",

year = "2023",

month = jun,

doi = "10.1038/s43587-023-00421-1",

language = "English",

volume = "3",

pages = "722--733",

journal = "Nature aging",

issn = "2662-8465",

publisher = "Nature Research",

number = "6",

}

COVID-19 Genomics Belgium Consortium, Cuypers, L, Keyaerts, E, Hong, SL, Gorissen, S, Menezes, SM, Starick, M, Van Elslande, J, Weemaes, M, Wawina-Bokalanga, T, Marti-Carreras, J, Vanmechelen, B, Van Holm, B, Bloemen, M, Dogne, J-M, Dufrasne, F, Durkin, K, Ruelle, J, De Mendonca, R, Wollants, E, Vermeersch, P, Boulouffe, C, Djiena, A, Broucke, C, Catry, B, Lagrou, K, Van Ranst, M, Neyts, J, Baele, G, Maes, P, André, E, Dellicour, S & Van Weyenbergh, J 2023, 'Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks', Nature aging, vol. 3, no. 6, pp. 722-733. https://doi.org/10.1038/s43587-023-00421-1

Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks. / COVID-19 Genomics Belgium Consortium; Cuypers, Lize; Keyaerts, Els; Hong, Samuel Leandro; Gorissen, Sarah; Menezes, Soraya Maria; Starick, Marick; Van Elslande, Jan; Weemaes, Matthias; Wawina-Bokalanga, Tony; Marti-Carreras, Joan; Vanmechelen, Bert; Van Holm, Bram; Bloemen, Mandy; Dogne, Jean-Michel; Dufrasne, François; Durkin, Keith; Ruelle, Jean; De Mendonca, Ricardo; Wollants, Elke; Vermeersch, Pieter; 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, Johan.

In: Nature aging, Vol. 3, No. 6, 06.2023, p. 722-733.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks

AU - COVID-19 Genomics Belgium Consortium

AU - Cuypers, Lize

AU - Keyaerts, Els

AU - Hong, Samuel Leandro

AU - Gorissen, Sarah

AU - Menezes, Soraya Maria

AU - Starick, Marick

AU - Van Elslande, Jan

AU - Weemaes, Matthias

AU - Wawina-Bokalanga, Tony

AU - Marti-Carreras, Joan

AU - Vanmechelen, Bert

AU - Van Holm, Bram

AU - Bloemen, Mandy

AU - Dogne, Jean-Michel

AU - Dufrasne, François

AU - Durkin, Keith

AU - Ruelle, Jean

AU - De Mendonca, Ricardo

AU - Wollants, Elke

AU - Vermeersch, Pieter

AU - Boulouffe, Caroline

AU - Djiena, Achille

AU - Broucke, Caroline

AU - Catry, Boudewijn

AU - Lagrou, Katrien

AU - Van Ranst, Marc

AU - Neyts, Johan

AU - Baele, Guy

AU - Maes, Piet

AU - André, Emmanuel

AU - Dellicour, Simon

AU - Van Weyenbergh, Johan

AU - Pierard, Denis

N1 - 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: Copyright 2023 Elsevier B.V., All rights reserved.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - Immunovirological screening

KW - environmental screening

KW - COVID-19

KW - post-vaccination

KW - nursing home outbreaks

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U2 - 10.1038/s43587-023-00421-1

DO - 10.1038/s43587-023-00421-1

M3 - Article

C2 - 37217661

VL - 3

SP - 722

EP - 733

JO - Nature aging

JF - Nature aging

SN - 2662-8465

IS - 6

ER -

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

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