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

par 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 Mendonça, Ricardo ;Wollants, Elke;Vermeersch, Pieter;COVID-19 Genomics Belgium Consortium, 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, ; [et al.]
Référence Nature aging, 3, 6, page (722-733)
Publication Publié, 2023-06-01

Article révisé par les pairs

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Résumé :

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.