High frequency of low-count monoclonal B-cell lymphocytosis in hospitalized COVID-19 patients

Low-count monoclonal B-cell lymphocytosis (MBLlo, <500 clonal B-cells/μL) is a highly prevalent condition in the general population (4% to 16% of otherwise healthy adults), which increases significantly with age.1-7 In most cases, clonal B-cells share phenotypic and cytogenetic features with chronic lymphocytic leukemia (CLL), but only a small fraction (≈1.8%) progresses to high-count MBL (MBLhi; ≥500 and <5000 clonal B-cells/μL)3 in the medium-term.8 However, previous reports showed that MBLlo subjects had an increased risk of severe infections in association with a (predominantly) secondary antibody deficiency,8-10 suggesting that MBLlo might be a risk marker for developing more severe infections.This work was supported by the Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación, Madrid, Spain, and FONDOS FEDER (a way to build Europe) grants CB16/12/00400 (CIBERONC), COV20/00386, and PI17/00399; the Consejería de Educación and the Gerencia Regional de Salud, Consejería de Sanidad from Junta de Castilla y León (Valladolid, Spain) grants SA109P20 and GRS-COVID-33/A/20; the European Regional Development Fund (INTERREG POCTEP Spain-Portugal) grant 0639-IDIAL-NET-3-3; and the CRUK (United Kingdom), Fundación AECC (Spain), and Associazione Italiana per la Ricerca Sul Cancro (Italy) “Early Cancer Research Initiative Network on MBL (ECRINM3)” ACCELERATOR award. G.O.-A. is supported by a grant from the Consejería de Educación, Junta de Castilla y León (Valladolid, Spain); B.F.-H. was supported by grant 0639-IDIAL-NET-3-3.Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality