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.

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

Background:Allergic rhinitis (AR) is a common disorder. The diagnosis is based on the concordance between allergy sensitization and history. Serum allergen specific immunoglobulin E (sIgE) assessment allows characterization of the relevant sensitizing allergens. Presently, Allergic Rhinitis and its Impact on Asthma (ARIA) classification subdivides AR based on symptoms severity and duration. However, the relationship between sIgE levels and symptom severity is still a matter of debate.Objective:Therefore, this study aimed at relating sIgE levels with symptom severity assessed by ARIA classification in a group of patients with AR.Methods:We enrolled 217 patients with AR (123 women; median age, 39.5 years). The sIgE levels (expressed in kUA/L) to house-dust mite were detected by the fluorescence enzyme immunoassay in peripheral blood samples. The IgE calibrators were traceable to the second international reference preparation 75/502 of human serum IgE from the World Health Organization. Symptom severity was assessed by ARIA classification.Results:We found a significant difference in sIgE levels in patients with mild intermittent versus mild persistent symptoms (p < 0.05), mild intermittent versus moderate-to-severe persistent symptoms (p < 0.001), moderate-to-severe intermittent versus moderate-to-severe persistent symptoms (p < 0.01), and mild persistent versus moderate-to-severe persistent symptoms (p < 0.05).Conclusion:Analysis of these findings indicated that the sIgE level to house-dust mite might be a reliable biomarker for symptom severity in patients with AR. This outcome might be clinically relevant, particularly in candidates for immunotherapy.

In the original publication of the article, the first name and last name of the author 'Federica Borrelli de Andreis' was incorrectly tagged in the xml. The correction citation of the author name should be read as 'Borrelli de Andreis F'.The original article was corrected.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p < 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p < 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p < 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.