Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response

André Santa Cruz (), Ana Mendes-Frias, Marne Azarias-da-Silva, Sónia André, Ana Isabel Oliveira, Olga Pires, Marta Mendes, Bárbara Oliveira, Marta Braga, Joana Rita Lopes, Rui Domingues, Ricardo Costa, Luís Neves Silva, Ana Rita Matos, Cristina Ângela, Patrício Costa, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, António Gil Castro, Jérôme Estaquier () and Ricardo Silvestre ()
Additional contact information
André Santa Cruz: University of Minho
Ana Mendes-Frias: University of Minho
Marne Azarias-da-Silva: INSERM-U1124, Université Paris Cité
Sónia André: INSERM-U1124, Université Paris Cité
Ana Isabel Oliveira: Hospital of Braga
Olga Pires: Hospital of Braga
Marta Mendes: Hospital of Braga
Bárbara Oliveira: Hospital of Braga
Marta Braga: Hospital of Braga
Joana Rita Lopes: Hospital of Braga
Rui Domingues: Hospital of Braga
Ricardo Costa: Hospital of Braga
Luís Neves Silva: Hospital of Braga
Ana Rita Matos: Hospital of Braga
Cristina Ângela: Hospital of Braga
Patrício Costa: University of Minho
Alexandre Carvalho: University of Minho
Carlos Capela: University of Minho
Jorge Pedrosa: University of Minho
António Gil Castro: University of Minho
Jérôme Estaquier: INSERM-U1124, Université Paris Cité
Ricardo Silvestre: University of Minho

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

Abstract: Abstract Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+β7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.

Date: 2023
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DOI: 10.1038/s41467-023-37368-1

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