SARS-CoV-2 sculpts the immune system

SARS-CoV-2 infection induces virus-reactive memory B cells expressing unmutated antibodies, suggesting their emergence from naive B cells. Yet, the dynamics of naïve virus-specific B cells and their impact on immunity and immunopathology remain unclear.

We longitudinally profiled SARS-CoV-2-specific B cell responses in 25 moderate to severe COVID-19 patients by high-dimensional flow cytometry and isotyping and subtyping ELISA. We also explored the relationship between B cell responses to SARS-CoV-2 and the activation of effector and regulatory cells of the innate or adaptive immune system.

We found a virus-specific antibody response with a wide range of classes and subclasses during acute infection, which evolved into an IgG1-dominated response during convalescence. Acute infection was associated with an increase in the number of circulating mature B cell progenitors and the unexpected expansion of virus-targeting naïve B cells.

The latter increased further during recovery with virus-specific memory B cells. In addition to a transient increase in CXCR3+ plasmablasts and extrafollicular memory B cells, most patients with COVID-19 showed persistent CD4+ and CD8+ T cell activation as well as transient or long-lasting changes in major innate immune cells. . Remarkably, virus-specific antibodies and naïve B-cell frequency were among the main variables defining distinct immune signatures associated with disease severity and inflammation.

In addition to providing new insights into the complexity of the immune response to SARS-CoV-2, our results indicate that de novo recruitment of mature B-cell precursors to the periphery may be central to the induction of immunity. antiviral.

To date, the rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected approximately 200 million people, resulting in more than four million deaths worldwide.1 SARS-CoV infection -2 causes coronavirus disease 2019 (COVID -19), which is characterized by a wide variety of clinical manifestations ranging from asymptomatic, acute respiratory distress syndrome (ARDS), multiple organ failure and death.2 Although such diversity in disease pathogenesis is partly explained by comorbidities and demographic factors, severe disease manifestations are strongly associated with dysregulated immune responses.

3, 4 Immune dysregulation in patients with severe COVID-19 is characterized by delayed and impaired responses to type I interferon that are associated with the inability to control the primary infection.5,6 Aberrant activation of im cells resulting innate cells leads to an exacerbated release of pro-inflammatory cytokines, causing inflammation and tissue damage7. Interestingly, interferon signaling and hyperinflammation may be associated with autoimmunity. Indeed, patients with severe COVID-19 develop autoantibodies against immunomodulatory proteins, including antibodies against type I interferon