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 - Wattiez, Ruddy
AU - Peeters, Michael
AU - Bakelants, Kate
AU - Denayer, Sarah
AU - Dufrasne, François E.
AU - Meex, Cécile
AU - Gillet, Laurent
AU - Artesi, Maria
AU - Hayette, Marie Pierre
AU - Bontems, Sébastien
AU - Bours, Vincent
AU - Gourzonès, Claire
AU - Ek, Olivier
AU - Bureau, Fabrice
AU - Kabamba, Benoit
AU - Gala, Jean Luc
AU - Bearzatto, Bertrand
AU - Ambroise, Jérôme
AU - Marchant, Arnaud
AU - Henin, Coralie
AU - Haerlingen, Benoit
AU - de Mendonca, Ricardo
AU - Delforge, Marie Luce
AU - Vael, Carl
AU - Berckmans, Lynsey
AU - Selhorst, Philippe
AU - Ariën, Kevin K.
AU - Hilbert, Pascale
AU - Degosserie, Jonathan
AU - Denis, Olivier
N1 - Publisher Copyright:
© 2023, The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85160051457&partnerID=8YFLogxK
U2 - 10.1038/s43587-023-00421-1
DO - 10.1038/s43587-023-00421-1
M3 - Article
AN - SCOPUS:85160051457
SN - 2662-8465
VL - 3
SP - 722
EP - 733
JO - Nature Aging
JF - Nature Aging
IS - 6
ER -
