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.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1 , OAS2 , or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

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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.

Obstructive sleep apnea syndrome (OSAS) which is frequently seen in men (9% for women and 24% for men), 1 is a syndrome characterized by repeated respiratory arrests due to partial or complete obstructions in the upper airway during sleep, decreased blood oxygen saturation, and short-term arousals. 2 Anatomic disorders that narrow the upper airway, advanced age, obesity, male sex, drugs, or substances that reduce muscle tone, and endocrine disorders are risk factors for OSAS. 3 Despite a recent decline in the smoking prevalence, tobacco use remains a significant global public health problem and is still the leading cause of preventable morbidity and mortality in the World. Nicotine is the main ingredient in tobacco products that is responsible for addiction, which contributes in the long-term to coronary heart disease, stroke,

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a simple, reliable, minimally invasive and effective procedure. However, a surgical technique may be required, if the results are negative. Therefore, there is a need for new studies to increase the diagnostic value of EBUS-TBNA and provide additional information to guide the biopsy in performing the procedure. Here, we aimed to investigate the diagnostic value of EBUS-TBNA and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in diagnosis of hilar and/or mediastinal lymph nodes (LNs). It was also aimed to determine the contributions of real-time ultrasonography (USG) images of LNs to distinguishing between the malignant and benign LNs during EBUS-TBNA, and in the diagnosis of anthracotic LNs. Material and Method: In the retrospective study including 545 patients, 1068 LNs were sampled by EBUS-TBNA between January 2015 and February 2020. EBUS-TBNA, 18-FDG PET/CT and images of USG were investigated in the diagnosis of mediastinal and/or hilar malignant, anthracotic and other benign LNs. Results: The sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were found as 79.5, 98.1, 89.5, and 91.7%, respectively. Mean maximum standardized uptake value (SUVmax) values of 18F-FDG PET/CT were 6.31±4.3 in anthracotic LNs and 5.07 ± 2.53 in reactive LNs. Also, mean SUVmax of malignant LNs was 11.02 ± 7.30 and significantly higher than that of benign LNs. In differentiation of malignant-benign tumors, considering the cut off value of 18F-FDG PET/CT SUVmax as 2.72, the sensitivity and specificity was 99.3 and 11.7%, but given the cut off value as 6.48, the sensitivity, specificity, positive predictive value and negative predictive value was found as 76.5, 64, 20.49, and 78.38% for benign LNs, respectively. Compared LNs as to internal structure and contour features, malignant LNs had most often irregular contours and heterogeneous density. Anthracotic, reactive and other benign LNs were most frequently observed as regular contours and homogeneous density. The difference between malignant and benign LNs was significant. Conclusion: EBUS can contribute to the differential diagnosis of malignant, anthracotic and other benign LNs. Such contributions can guide clinician bronchoscopists during EBUS-TBNA. The triple modality of EBUS-TBNA, 18FDG PET/CT, and USG may increase the diagnostic value in hilar and mediastinal lymphadenopathies.

INTRODUCTION: The primary aim of the study was to compare the laboratory and radiological parameters of COVID-19 positive and negative patients confirmed by Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR), and Chest Computed Tomography (CCT) of patients admitting with the suspicion of COVID-19. The secondary purpose of the study was to find objective parameters to speed up the clinician for further examination, treatment or referral decision in COVID-19 suspicion. MATERIAL AND METHODS: A total of 61 COVID-19 suspected patients were evaluated in the study. Swab samples were taken for RT-PCR analysis. CCT was taken for 42 patients who described dyspnea. According to CCT and RT-PCR results, the patient population was divided into 2 groups as COVID-19 positive group (n = 32); and COVID-19 negative group (n = 29). Between two groups; demographic, clinical, laboratory and radiological parameters were compared. RESULTS: Male gender (p = 0.03), PLR value (p = 0.021) and CO-RADS scores were higher in the COV-ID-19 positive group. Oxygen saturation (SaO 2) (p = 0.027) and PCT, WBC, Neutrophil count, Lymphocyte count values were significantly low in COVID-19 positive group (p = 0.03, p = 0.001, p = 0.017, p = 0.021, respectively). PLR showed a positive correlation with fever, CRP, neutrophil count and NLR, which are indicators of inflammation. CONCLUSIONS: SaO 2 , WBC, lymphocyte count, neutrophil count and low PCT levels, and PLR elevation showed a significant difference in COVID-19 patients in our retrospective cohort study examining the Turkish population. We believe that these results will allow clinicians to make quick decisions in patient management more simply.