Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19

Lenti, Marco Vincenzo; Aronico, Nicola; Pellegrino, Ivan; Boveri, Emanuela; Giuffrida, Paolo; Borrelli de Andreis, Federica; Morbini, Patrizia; Vanelli, Laura; Pasini, Alessandra; Ubezio, Cristina; Melazzini, Federica; Rascaroli, Alessandro; Antoci, Valentina; Merli, Stefania; Di Terlizzi, Francesco; Sabatini, Umberto; Cambiè, Ginevra; Tenore, Annamaria; Picone, Cristina; Vanoli, Alessandro; Arcaini, Luca; Baldanti, Fausto; Paulli, Marco; Corazza, Gino Roberto; Di Sabatino, Antonio

Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count < 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections.