443 COVID19 DISEASE SEVERITY INFLUENCES THE EXPRESSION OF MARKERS OF DURABILITY IN MEMORY B CELLS

443 COVID19 disease severity influences the expression of markers of durability in memory B cells

443 COVID19 disease severity influences the expression of markers of durability in memory B cells

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OBJECTIVES/GOALS: Studies have shown that SARS-CoV-2 specific memory B cells can be maintained at least a year after exposure.However, reports show an altered B cell response during infection in severe wnba COVID-19 cases.This study aims to describe the B cell response during COVID-19 convalescence with a focus on signatures that contribute to durable and robust immunity.METHODS/STUDY POPULATION: Our study cohort consisted of individuals who had recovered from non-severe (hospitalized) or severe (hospitalized and requiring invasive mechanical ventilation) COVID-19.In our comparative analysis, samples from both groups were carefully matched to fall within 4-5 weeks post-symptom onset.

We also performed a longitudinal analysis of non-severe patients with sampling ending 5 months post-symptom onset.Using high parameter flow cytometry, we characterized the phenotype of memory B cells using 19 distinct cell markers and fluorescently labeled probes to identify B cells reactive with SARS-CoV-2 spike and receptor-binding domain protein.Additionally, serum collected from individuals was used to quantify antibody titers.RESULTS/ANTICIPATED RESULTS: The frequency of spike-specific B cells and serum antibody titers were similar between severe and non-severe groups.However, we observed that individuals recovered from severe COVID-19 have a significantly reduced frequency of spike specific IgG+ Vacuum Sealers memory B cells expressing Tbet and FcRL5 (markers associated with long lived immunity).

In the non-severe patients, we observed IgG+Tbet+ B cells targeting the spike protein peak at 2-3 weeks post-symptom onset, decrease by almost fifty percent 4-5 weeks post-symptom onset, and return to baseline 5 months post-symptom onset.Our study also validated previous findings of a short-lived primary response of IgM+ B cells targeting the spike protein.DISCUSSION/SIGNIFICANCE: Our findings highlight potential implications for long-term immunity against re-infection or severity of the resulting disease in patients with severe COVID-19.Further investigation will be necessary to determine whether the maintenance of immunological protection is hindered in patients who overcame severe COVID-19.

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