Abstract
Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected cells. Surprisingly, frequencies of SARS-CoV-2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualitative defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.
Highlights
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is characterized by a large heterogeneity in disease severity, ranging from asymptomatic to fatal cases, and in antiviral immune responses [1]
A more extensive and exhaustive approach was applied here to compare the B cell repertoire of convalescent patients recovering of a severe form of the disease (SP) to the repertoire of convalescent healthcare personnel (HP) without pre-existing immune system alterations, who recovered from a mild form of COVID-19
Among the 11 clones, 6 were specific for the receptor binding domain (RBD) domain, 1 was specific of the S1 domain of the spike protein but did not recognize the RBD domain, and 4 clones stained SARS-CoV-2 infected BGM cells, but were not reactive against the tested antigens. These results demonstrate that the frequency of circulating SARS-CoV-2 reactive B cells does not correlate with the plasma levels of antiviral Ab in both SP and HP
Summary
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is characterized by a large heterogeneity in disease severity, ranging from asymptomatic to fatal cases, and in antiviral immune responses [1]. Several quantitative and qualitative defects affect peripheral T- and B cells in the most severe forms of coronavirus disease 2019 (COVID-19) [2,3,4] In these patients, the abnormal stability of CD8+ and CD4+ T cell activation suggests a functional T cell dysregulation and disruption of a coordinated T cell–B cell interaction, resulting in higher humoral immune responses [5,6,7,8]. It leads to the emergence of oligoclonal B cell populations with high serum oligoclonality, and to the presence of autoAb, against coagulation and vessel targets [14,15] These comorbidities have in common chronic systemic low-grade inflammation, with an abnormal production of pro-inflammatory cytokines and the impairment of T cell mediated immune response involved in host defense [16,17,18,19]. These immune defects affect several critical pathways that support the cooperation between T cells and B cells, such as the CD40/CD40 ligand pathway, which are probably even more deregulated by the inflammation caused by the SARS-CoV-2 infection
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