Axel Schulz

DRFZ, Berlin, Germany

Cutting Edge Session Part I: Wednesday, September 29^th, 2021: 4:00pm – 5:00pm

Severe COVID-19 is characterized by an increased induction of peripheral plasmablasts with an aberrant CD62L⁺HLA-DR^low phenotype

Background

The new pandemic coronavirus SARS-CoV-2 emerged in late 2019 and causes acute respiratory syndrome, leading to hospitalization, mechanical ventilation, and death in severe cases. Acutely induced plasmablasts (PB) play a central role in the adaptive immune response against SARS-CoV-2 by producing virus-specific, potentially neutralizing antibodies that help to resolve the infection. Here, we investigated and compared the dynamics and phenotypes of PB in the course of mild and severe SARS-CoV-2 infections.

Methods

We used two mass cytometric datasets that included up to three different time points of 9 severe (WHO 5-7) and 8 mild (WHO 2-4) COVID-19 cases, as well as 9 healthy donors (HD), previously analyzed for dysregulations in the myeloid compartment (Schulte-Schrepping et al., 2020, Cell). CD38^hiCD27^hi PB were identified using manual gating and opt-SNE and further characterized in OMIQ.ai. The use of SmartTube technology for whole blood preservation ensured the analysis of PB frequencies and phenotypes unaffected by any blood processing method.

Results

We observed elevated frequencies and absolute counts of PB in both severe and mild COVID-19 courses compared to HD. At early time points (day 4 – 12 post symptom onset) severe cases showed higher PB counts and frequencies among B cells, compared to patients with a mild course of disease (median severe 29%; mild, 19%; p=0.09). We further observed phenotypical differences of PB between both groups. Severe cases showed substantially higher proportions of CD62L⁺HLA-DR^low PB (p=0.06) and tended to have lower proportions of CD62L^–HLA-DR^hi PB (p=0.2) than mild cases, an observation that became even more pronounced when the severely affected cohort was stratified by fatal outcome (p=0.02).

Conclusion

The strong induction of abberant CD62L⁺HLA-DR^low PB in peripheral blood, rarely detectable in steady state or induced by systemic vaccination in healthy controls, may indicate an inadequante PB response in severe SARS-CoV-2 infections. Their appearance early after symptom onset could help identify patients at risk of developing a severe or fatal course of COVID-19.