Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infectionImmunity and inflammaion in post-acute sequelae of SARS-CoV-2 infection.

SARS-CoV-2 infection is known to result in a range of symptoms with varying degrees of acute-phase severity. In a subset of individuals, an equally diverse collection of long-term sequelae has been reported after convalescence. As survivorship and therefore the number of individuals with 'long-COVID' continues to grow, an understanding of the prevalence, origins, and mechanisms of post-acute sequelae manifestation is critically needed. Here, we will explore proposed roles of the anti-SARS-CoV-2 immune response in the onset, severity, and persistence of SARS-CoV-2 post-acute sequelae. We discuss the potential roles of persistent virus and autoantigens in this syndrome, as well as the contributions of unresolved inflammation and tissue injury. Furthermore, we highlight recent evidence demonstrating the potential benefits of vaccination and immunity in the resolution of post-acute symptoms.

Simultaneous analysis of antigen-specific B and T cells after SARS-CoV-2 infection and vaccination.

Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B and T cell tandem lymphocyte evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS-CoV-2 Spike reactive T and B cells using an activation induced marker (AIM) T cell assay and dual-color B cell antigen probes. Using this assay, we demonstrate that antigen-specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS-CoV-2 infection.

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.