Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19

Meng Yu, Afandi Charles, Alberto Cagigi, Wanda Christ, Björn Österberg, Sara Falck-Jones, Lida Azizmohammadi, Eric Åhlberg, Ryan Falck-Jones, Julia Svensson, Mu Nie, Anna Warnqvist, Fredrika Hellgren, Klara Lenart, Rodrigo Arcoverde Cerveira, Sebastian Ols, Gustaf Lindgren, Ang Lin, Holden Maecker, Max Bell, Niclas Johansson, Jan Albert, Christopher Sundling, Paulo Czarnewski, Jonas Klingström, Anna Färnert, Karin Loré and Anna Smed-Sörensen ()
Additional contact information
Meng Yu: Karolinska University Hospital
Afandi Charles: Karolinska University Hospital
Alberto Cagigi: Karolinska University Hospital
Wanda Christ: Karolinska Institutet
Björn Österberg: Karolinska University Hospital
Sara Falck-Jones: Karolinska University Hospital
Lida Azizmohammadi: Karolinska University Hospital
Eric Åhlberg: Karolinska University Hospital
Ryan Falck-Jones: Karolinska Institutet
Julia Svensson: Karolinska University Hospital
Mu Nie: Karolinska University Hospital
Anna Warnqvist: Karolinska Institutet
Fredrika Hellgren: Karolinska University Hospital
Klara Lenart: Karolinska University Hospital
Rodrigo Arcoverde Cerveira: Karolinska University Hospital
Sebastian Ols: Karolinska University Hospital
Gustaf Lindgren: Karolinska University Hospital
Ang Lin: Karolinska University Hospital
Holden Maecker: Stanford University School of Medicine
Max Bell: Karolinska Institutet
Niclas Johansson: Karolinska Institutet
Jan Albert: Karolinska Institutet
Christopher Sundling: Karolinska Institutet
Paulo Czarnewski: Stockholm University
Jonas Klingström: Karolinska Institutet
Anna Färnert: Karolinska Institutet
Karin Loré: Karolinska University Hospital
Anna Smed-Sörensen: Karolinska University Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.

Date: 2023
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DOI: 10.1038/s41467-023-37835-9

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