Contrasting immune responses in COVID-19: insights from healthcare workers and infected patients on plasmablast, pDC, and NK cell dynamics

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted significant variability in disease severity, ranging from asymptomatic cases to severe acute respiratory distress syndrome. Objective: Understanding the immune responses that contribute to this variability, particularly among healthcare workers (HCWs) frequently exposed to the virus, is essential. Materials and methods: This was a prospective single-center longitudinal cohort study. We included hospitalized COVID-19+ patients, classified as having mild or moderate-to-severe symptoms, and unvaccinated HCWs with low susceptibility. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed using flow cytometry. We measured the frequencies of key immune subsets, including plasmablasts, plasmacytoid dendritic cells (pDCs), and Natural Killer (NK) cells. SARS-CoV-2 neutralizing antibodies (NAbs) were quantified using pseudotyped HIV particles. Results: COVID-19+ patients exhibited a significant increase in plasmablasts, a B-cell subset responsible for producing neutralizing antibodies, which correlated with disease severity (p=0.0082). Conversely, uninfected HCWs had low levels of plasmablasts but significantly higher levels of plasmacytoid dendritic cells (pDCs) (p