Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential, although their origins and resolution have remained unclear. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity, as a dominant feature of severe and critical COVID-19 (refs.

Response under pressure: deploying emerging technologies to understand B-cell-mediated immunity in COVID-19.

Critical technological advances have enabled the rapid investigations into the immune responses elicited by SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. In this Comment, we discuss the cutting-edge methods used to deconvolute the B cell responses against this virus, and the significant impact they have had in the ongoing public health crisis.

One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses.

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection.

Background: SARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses.

Relaxed peripheral tolerance drives broad autoreactivity in severe COVID-19.

An emerging feature of COVID-19 is the identification of autoreactivity in patients with severe disease that may contribute to disease pathology, however the origin and resolution of these responses remain unclear. Previously, we identified strong extrafollicular B cell activation as a shared immune response feature between both severe COVID-19 and patients with advanced rheumatic disease. In autoimmune settings, this pathway is associated with relaxed peripheral tolerance in the antibody secreting cell compartment and the generation of autoreactive responses.

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings.