Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month timeframe. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both pre- and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sub-lineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly-reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants.

SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 Milan outbreak

ObjectivesThe Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The epidemiological trends of mild COVID-19 are however still unknown. The aim of this study was to examine the seroprevalence of SARS-CoV-2 infection in healthy asymptomatic adults, the risk factors, and laboratory correlates. DesignWe conducted a cross-sectional study during the outbreak. Presence of anti-SARS-CoV-2 IgM/IgG antibodies against the Nucleocapsid protein was assessed by a lateral flow immunoassay. SettingBlood center at a leading academic hospital serving as COVID-19 referral center. ParticipantsWe considered a random sample of blood donors since the start of the outbreak (February 24th to April 8th 2020, n=789). Main outcome measuresThe main outcome was the prevalence of IgG/IgM anti-SARS-CoV-2 antibodies. ResultsThe test had a 98.3% specificity and 100% sensitivity, and for IgG+ was validated in a subset by an independent ELISA against the Spike protein (N=34, P<0.001). At the start of the outbreak, the overall seroprevalence of SARS-CoV-2 was 4.6% (2.3 to 7.9; P<0.0001 vs. 120 historical controls). During the study period characterized by a gradual implementation of social distancing measures, there was a progressive increase in seroprevalence to 7.1% (4.4 to 10.8), due to a rise in IgG+ to 5% (2.8 to 8.2; P=0.004 for trend, adjusted weekly increase 2.7{+/-}1.3%), but not of IgM+ (P=NS). At multivariate logistic regression analysis, seroconversion to IgG+ was more frequent in younger (P=0.043), while recent infections (IgM+) in older individuals (P=0.002). IgM+ was independently associated with higher triglycerides, eosinophils, and lymphocytes (P<0.05). ConclusionsSARS-CoV-2 infection was already circulating in Milan at the outbreak start. Social distancing may have been more effective in younger individuals, and by the end of April 4.4-10.8% of healthy adults had evidence of seroconversion. Asymptomatic infection may affect lipid profile and blood count. SUMMARY BOXO_ST_ABSWhat is already know on this topicC_ST_ABSO_LISARS-CoV-2 causes COVID-19, associated with a high mortality rate, but may be asymptomatic in a still undefined fraction of individuals. C_LIO_LICOVID-19 is associated with altered hematological, inflammatory and biochemical parameters, but the laboratory correlates of non-severe infection are unknown. C_LIO_LIA severe COVID-19 outbreak severely hit Milan at the end of February 2020, but the number of infected individuals and risk factors remain unclear. C_LI What this study addsO_LISARS-CoV-2 was already circulating in Milan at the COVID-19 outbreak start on February 2020, with only 1 in 20 infected individuals being symptomatic and diagnosed. C_LIO_LISocial distancing may have been more effective in reducing new infections in younger individuals, and by the end of April 4.4-10.8% of healthy asymptomatic adults had evidence of seroconversion. C_LIO_LIAsymptomatic infection may affect lipid profile and be associated with higher circulating lymphocytes and eosinophils. C_LI

GENOMIC CHARACTERISATION AND PHYLOGENETIC ANALYSIS OF SARS-COV-2 IN ITALY

This report describes the isolation, the molecular characterization and the phylogenetic analysis of the first three complete genomes of SARS-CoV-2 isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.