Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Purpose of the studyThe aim of this study was to investigate the relationship of B cell-mediated immunity with disease severity and mortality in patients with COVID-19.Study designIn this retrospective cohort and single-centre study, 208 patients with laboratory-confirmed COVID-19 were recruited. A COVID-19 severity score, ranging from 0 to 10, was used to evaluate associations between various factors. Serum immunoglobulin levels and the number of cells in B lymphocyte subsets were measured and their association with disease severity and mortality in patients with COVID-19 examined.ResultsThe median age of the patients was 50 (35–63) years and 88 (42%) were female. The number of deceased patients was 17. The median COVID-19 severity score was 8 (6–8) in deceased patients and 1 (0–2) in survivors. Deceased patients had significantly lower levels of total B lymphocytes, naive B cells, switched memory B cells, and serum IgA, IgG, IgG1 and IgG2 than recovered patients (all p<0.05). In addition, a significant negative correlation was found between the number of these parameters and COVID-19 severity scores. Decrease in the number of total B cells and switched memory B cells as well as lower serum IgA, IgG and IgG1 levels were independent risk factors for mortality in patients with COVID-19.ConclusionIn the present study, the prognosis of patients with COVID-19 was shown to be associated with the B cell subset and serum immunoglobulin levels.

The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) vary widely among populations. Mucosal immunity is the first barrier to pathogens' entry into the body.Immunoglobulin A (IgA) is the main antibody of mucosal immunity. We explored the relationship between selective immunoglobulin A deficiency (SIgAD) and the severity of COVID-19. We included 424 patients (203 females) with COVID-19. Eleven patients had SIgAD. Laboratory data on patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored by logistic regression analysis. In univariate logistic regression analysis, the risk of severe disease in COVID-19 patients with SIgAD was approximately 7.7-fold higher than in the other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, p = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, p = 0.026) higher in multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts, and negatively correlated with C-reactive protein (CRP) levels, which were found as a risk factor for severe COVID-19.In SIgAD patients, the number of SARS-CoV-2 viruses that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.

Objective: The effect of the COVID-19 pandemic on mental health in the long term is unclear. We evaluated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)–related transmission fear and mental-health disorders in populations at high risk for COVID-19. Materials and Methods: Healthcare workers and patients with primary immunodeficiency disorders (PIDs), severe asthma, malignancy, cardiovascular disease, hypertension, and diabetes mellitus were included in the study. The hospital anxiety and depression scale (HADS) and Fear of Illness and Virus Evaluation (FIVE) scales were applied during face-to-face interviews. Results: There was a total of 560 participants, 80 per group; 306 (55%) were female. The FIVE and HADS-A scale scores of health care workers were significantly higher than the other groups (p = 0.001 and 0.006). The second-highest scores were in patients with PID. There was no significant difference between the groups in HADS-D scores (p = 0.07). There was a significant positive correlation between FIVE scale scores and anxiety (r = 0.828; p < 0.001) and depression (r = 0.660; p < 0.001). The FIVE scale had significant discriminatory power for anxiety (AUC = 0.870, 95% confidence interval [CI] = 0.836–0.904; p < 0.0001) and depression (area under the curve = 0.760, 95% CI = 0.717–0.803; p < 0.0001). Conclusion: During the COVID-19 pandemic, mental-health disorders may develop in patients with comorbidities, especially healthcare workers. They should be referred to mental-health centers. Keywords: Asthma, COVID-19, fear of virus transmission, mental health, primary immunodeficiency