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

• Published in: Nature communications Vol. 14; no. 1; pp. 2164 - 14
• Main Authors: Yu, Meng, Charles, Afandi, Cagigi, Alberto, Christ, Wanda, Österberg, Björn, Falck-Jones, Sara, Azizmohammadi, Lida, Åhlberg, Eric, Falck-Jones, Ryan, Svensson, Julia, Nie, Mu, Warnqvist, Anna, Hellgren, Fredrika, Lenart, Klara, Arcoverde Cerveira, Rodrigo, Ols, Sebastian, Lindgren, Gustaf, Lin, Ang, Maecker, Holden, Bell, Max, Johansson, Niclas, Albert, Jan, Sundling, Christopher, Czarnewski, Paulo, Klingström, Jonas, Färnert, Anna, Loré, Karin, Smed-Sörensen, Anna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/1619/554/1898/1270; 631/250/2152/2153/1291; Antibodies; Avidity; CD4 antigen; Cell interactions; Coronaviruses; COVID-19; Helper cells; Humanities and Social Sciences; Humans; Immune response (humoral); Immunological memory; Lymph nodes; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Memory cells; multidisciplinary; Neutralization; Plasma Cells; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; T Follicular Helper Cells; T-Lymphocytes, Helper-Inducer; Viral diseases; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37835-9

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. T follicular helper cells (Tfh) enhance antibody responses and can circulate or be resident in lymph nodes. Here the authors show that during acute SARS-CoV-2 infection, circulating Tfh cells correlate with antibody titres and plasmablast levels but in more severe COVID-19 cases, cTfh generation is delayed.