Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against 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 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Efficacy of a multi-component intervention to reduce workplace sedentary behaviour in office workers

Objective: To investigate the efficacy of a work-based multicomponent intervention to reduce office workers’ sitting time. Methods: Offices (n=12; 89 workers) were randomised into an 8-week intervention (n=48) incorporating organisational, individual, and environmental elements or control arm. Sitting time, physical activity and cardiometabolic health were measured at baseline and after the intervention. Results: Linear mixed modelling revealed no significant change in workplace sitting time, but changes in workplace prolonged sitting time (-39 min/shift), sit-upright transitions (7.8 per shift) and stepping time (12 min/shift) at follow-up were observed, in favour of the intervention group (p<0.001). Results for cardiometabolic health markers were mixed. Conclusions: This short multicomponent workplace intervention was successful in reducing prolonged sitting and increasing physical activity in the workplace, although total sitting time was not reduced and the impact on cardiometabolic health was minimal.

Novel non-synonymous polymorphisms in the COX-1 gene in Turkish pediatric patients with cardiovascular anomalies

Variation in the gene encoding cyclooxygenase-1 (COX-1) is involved in the process of aspirin resistance. This study investigated the genetic variations in the COX-1 gene. The 4 coding regions of the human COX-1 gene in 90 pediatric patients (median age of 6.5 months, 55% males) with cardiovascular anomalies were screened using DNA sequencing. Twenty coding-region variants causing amino acid substitutions as well as 2 new non-synonymous polymorphisms were identified. All variants were compared with an independent Caucasian population (N = 24 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulted in amino acid changes occurring at a frequency >5% (W8R, P17L, Q41Q, Q240Q, D189E, and P188P). In addition, 2 new non-synonymous polymorphisms (F200L and D189E) were identified. These findings demonstrated novel genetic variants of the human COX-1 gene. Future studies characterizing the functional impact of these variants are warranted