Homotypic and heterotypic immune responses to Omicron variant in immunocompromised patients in diverse clinical settings

Victor H. Ferreira, Javier T. Solera, Queenie Hu, Victoria G. Hall, Berta G. Arbol, W. Rod Hardy, Reuben Samson, Tina Marinelli, Matthew Ierullo, Avneet Kaur Virk, Alexandra Kurtesi, Faranak Mavandadnejad, Beata Majchrzak-Kita, Vathany Kulasingam, Anne-Claude Gingras, Deepali Kumar and Atul Humar ()
Additional contact information
Victor H. Ferreira: University Health Network
Javier T. Solera: University Health Network
Queenie Hu: Sinai Health
Victoria G. Hall: University Health Network
Berta G. Arbol: University Health Network
W. Rod Hardy: Sinai Health
Reuben Samson: Sinai Health
Tina Marinelli: University Health Network
Matthew Ierullo: University Health Network
Avneet Kaur Virk: University Health Network
Alexandra Kurtesi: Sinai Health
Faranak Mavandadnejad: University Health Network
Beata Majchrzak-Kita: University Health Network
Vathany Kulasingam: University Health Network
Anne-Claude Gingras: Sinai Health
Deepali Kumar: University Health Network
Atul Humar: University Health Network

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4+ and CD8+ T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection.

Date: 2022
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DOI: 10.1038/s41467-022-32235-x

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