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.
Giriş Son yıllarda yayınlanan makaleler incelendiğinde, anestezistlerin preoperatif muayene sırasında her hastayı obstrüktif uyku apnesi (OUA) olasılığı açısından değerlendirmesinin gerekli olduğu anlaşılmaktadır. Bu gereklilik başlıca iki nedene dayanır; ilki, OUA hastalarının %80-90'ının tanı konmamış durumda olmalarıdır (1). İkinci neden ise, Amerikan Anestezistler Birliği'nin (ASA) 2006'da yayımladığı bir kılavuzla, cerrahi hastalara preoperatif dönemde OUA açısından tarama yapılmasını önermiş olmasıdır (2). Preoperatif dönemde kullanılacak uygun bir tarama ile OUA olasılığı yüksek olan hastalar belirlenip, anestezistlerin peroperatif dönemde karşı karşıya kalabilecekleri riskler en aza indirilebilir.Temel özellikleri uykuda solunumun bozulması, horlama ve gün içinde aşırı uyku hali olan OUA, erişkin popülasyonda kadınlarda %2, erkeklerde %4 oranında görülmektedir (3). OUA'nın cerrahi hastalardaki görülme sıklığına dair rakamlar değişkenlik gösterse de, bariatrik cerrahi gibi bazı özel hasta gruplarında çok yüksek oranlarda (%78) izlendiği bildirilmektedir (4-8). Peroperatif komplikasyonlar ile OUA şiddeti arasında doğrudan bir ilişki olduğu bilindiği için, hangi nedenle cerrahi geçirecek olursa olsun OUA hastalarına önceden tanı konularak gereken önlemlerin alınması büyük önem taşımaktadır (2). Bu hastalarda anestezi indüksiyonu sırasında havayolu sağlanmasında zorlukla karşılaşılabilir (9). Ekstübasyondan hemen sonra solunum yolu obstrüksiyonu görülebileceği gibi, postoperatif dönemde verilen Methods:In 110 adult patients who were admitted to the Sleep Clinic for polysomnography with an initial diagnosis of obstructive sleep apnoea, the STOP-Bang questionnaire was used to calculate the sensitivity, specificity, negative predictive value, positive predictive value and likelihood ratios. Results:In the study, no significant difference was obtained between two sexes for the presence of high risk of obstructive sleep apnoea (p>0.05). When apnoea-hypopnoea index (AHI) ≤5 patients and AHI >5 patients were compared, no significant differences were found in the values of age, sex and body mass index (p>0.05). Mean AHI value was 1.4 in AHI ≤5 patients, while it was 33.8 in AHI >5 patients (p<0.05). Although both STOP and STOP-Bang screening tests have a high sensitivity (>90%) in various severities of OSA (AHI >5, AHI >15 and AHI >30), their specificities were found to be low. As the severity of OSA increases, the positive predictive values of both tests were decreased, while the negative predictive values were increased. Conclusion
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.
Background: This study evaluates the influence of sniffing position combined with mouth opening on the effectiveness of facemask ventilation in paralyzed pediatric patients undergoing adenotonsillectomy during sevoflurane-N 2 O anesthesia. Methods: After Institutional Ethics Committee approval, 40 children 5-11 years of age who were scheduled for an elective adenotonsillectomy operation were enrolled in this prospective randomized study. After routine monitoring and pre-oxygenation, anesthesia was induced with sevoflurane 8% in a mixture of 50% N 2 O-O 2 . Three minutes after the administration of vecuronium, the sequence of the positions was randomized. Three positions were applied during facemask ventilation: Position CN (closed mouthneutral head and neck position), position CS (closed mouth-sniffing position) and position OS (opened mouthsniffing position). Volume-controlled ventilation was started. Peak inspiratory pressure (PIP), tidal volume (V T ), expired tidal volume (V Texp ) and end-tidal CO 2 pressure were recorded. The percent of leakage was calcu-
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