Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort

Dominik Menges, Kyra D. Zens, Tala Ballouz, Nicole Caduff, Daniel Llanas-Cornejo, Hélène E. Aschmann, Anja Domenghino, Céline Pellaton, Matthieu Perreau, Craig Fenwick, Giuseppe Pantaleo, Christian R. Kahlert, Christian Münz, Milo A. Puhan () and Jan S. Fehr
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Dominik Menges: University of Zurich (UZH)
Kyra D. Zens: University of Zurich (UZH)
Tala Ballouz: University of Zurich (UZH)
Nicole Caduff: University of Zurich (UZH)
Daniel Llanas-Cornejo: University of Zurich (UZH)
Hélène E. Aschmann: University of Zurich (UZH)
Anja Domenghino: University of Zurich (UZH)
Céline Pellaton: Lausanne University Hospital (CHUV), University of Lausanne (UNIL)
Matthieu Perreau: Lausanne University Hospital (CHUV), University of Lausanne (UNIL)
Craig Fenwick: Lausanne University Hospital (CHUV), University of Lausanne (UNIL)
Giuseppe Pantaleo: Lausanne University Hospital (CHUV), University of Lausanne (UNIL)
Christian R. Kahlert: Cantonal Hospital St. Gallen
Christian Münz: University of Zurich (UZH)
Milo A. Puhan: University of Zurich (UZH)
Jan S. Fehr: University of Zurich (UZH)

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.

Date: 2022
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DOI: 10.1038/s41467-022-32573-w

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