SARS-CoV-2 sculpts the immune system to induce sustained virus-specific naïve-like and memory B cell responses

SARS-CoV-2 infection induces virus-reactive memory B cells expressing unmutated antibodies, which hints at their emergence from naive B cells. Yet, the dynamics of virus-specific naive B cells and their impact on immunity and immunopathology remain unclear. Here, we longitudinally studied moderate to severe COVID-19 patients to dissect SARS-CoV-2-specific B cell responses overtime. We found a broad virus-specific antibody response during acute infection, which evolved into an IgG1-dominated response during convalescence. Acute infection was associated with increased mature B cell progenitors in the circulation and the unexpected expansion of virus-targeting naive-like B cells that further augmented during convalescence together with virus-specific memory B cells. In addition to a transitory increase in tissue-homing CXCR3+ plasmablasts and extrafollicular memory B cells, most COVID-19 patients showed persistent activation of CD4+ and CD8+ T cells along with transient or long-lasting changes of key innate immune cells. Remarkably, virus-specific antibodies and the frequency of naive B cells were among the major variables defining distinct immune signatures associated with disease severity and inflammation. Aside from providing new insights into the complexity of the immune response to SARS-CoV-2, our findings indicate that the de novo recruitment of mature B cell precursors into the periphery may be central to the induction of antiviral immunity.

SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19

The production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.

Risk factors for SARS-CoV-2 infection, hospitalisation, and death in Catalonia, Spain: a population-based cross-sectional study

OBJECTIVETo identify the different subpopulations that are susceptible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalisation or death due to coronavirus disease 2019 (COVID-19) in Catalonia, Spain. DESIGNCross-sectional study. SETTINGData collected from the Catalan Health Surveillance System (CatSalut) in Catalonia, a region of Spain. PARTICIPANTSUsing data collected between 1 March and 1 June 2020, we conducted the following comparative analyses: people infected by SARS-CoV-2 (328 892) vs Catalonias entire population (7 699 568); COVID-19 cases who required hospitalisation (37 638) vs cases who did not require hospitalisation (291 254); and COVID-19 cases who died during the study period vs cases who did not die during the study period (12 287). MAIN OUTCOME MEASURESThree clinical outcomes related to COVID-19 (infection, hospitalisation, or death). We analysed sociodemographic and environment variables (such as residing in a nursing home) and the presence of previous comorbidities. RESULTSA total of 328 892 cases were considered to be infected with SARS-CoV-2 (4.27% of total population). The main risk factors for the diagnostic were: female gender (risk ratio [RR] =1.49; 95% confidence interval [95% CI] =1.48-1.50), age (4564 years old; RR=1.02; 95% CI=1.01-1.03), high comorbidity burden (GMA index) (RR=3.03; 95% CI=2.97-3.09), reside in a nursing home (RR=11.82; 95% CI=11.66-11.99), and smoking (RR=1.06; 95% CI=1.05-1.07). During the study period, there were 37 638 (11.4 %) hospitalisations due to COVID-19, and the risk factors were: male gender (RR=1.45; 95% CI=1.43-1.48), age > 65 (RR=2.38; 95% CI=2.28-2.48), very low individual income (RR=1.03; 95% CI=0.97-1.08), and high burden of comorbidities (GMA index) (RR=5.15; 95% CI=4.89-5.42). The individual comorbidities with higher burden were obesity (RR=1.23; 95% CI=1.20-1.25), chronic obstructive pulmonary disease (RR=1.19; 95% CI=1.15-1.22), heart failure (RR=1.19; 95% CI=1.16-1.22), diabetes mellitus (RR=1.07; 95% CI=1.04-1.10), and neuropsychiatric comorbidities (RR=1.06; 95% CI=1.03-1.10). A total of 12 287 deaths (3.73%) were attributed to COVID-19, and the main risk factors were: male gender (RR=1.73; 95% CI=1.67-1.81), age > 65 (RR=37.45; 95% CI=29.23-47.93), residing in a nursing home (RR=9.22; 95% CI=8.81-9.65), and high burden of comorbidities (GMA index) (RR=5.25; 95% CI=4.60-6.00). The individual comorbidities with higher burden were: heart failure (RR=1.21; 95% CI=1.16-1.22), chronic kidney disease (RR=1.17; 95% CI=1.13-1.22), and diabetes mellitus (RR=1.10; 95% CI=1.06-1.14). These results did not change significantly when we considered only PCR-positive patients. CONCLUSIONSFemale gender, age between 45 to 64 years old, high burden of comorbidities, and factors related to environment (nursing home) play a relevant role in SARS-CoV-2 infection and transmission. In addition, we found risk factors for hospitalisation and death due to COVID-19 that had not been described to date, including comorbidity burden, neuro-psychiatric disorders, and very low individual income. This study supports interventions for transmission control beyond stratify-and-shield strategies focused only on protecting those at risk of death. Future COVID-19 studies should examine the role of gender, the burden of comorbidities, and socioeconomic status in disease transmission, and should determine its relationship to workplaces, especially healthcare centres and nursing homes.

Effects of environmental factors on severity and mortality of COVID-19

BackgroundMost respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented. MethodsWe examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. FindingsMeta-analysis of the mortality risk in eight European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, p<0.001) and per increase in ambient temperature of one degree Celsius to be 0.854 (0.773-0.944, p=0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to Intensive Care Unit and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. InterpretationSeverity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation. Mucosal barrier and mucociliary clearance can significantly decrease viral load and disease progression, and their inactivation by low relative humidity of indoor air might significantly contribute to severity of the disease.