The relationship between autoantibodies targeting GPCRs and the renin-angiotensin system associates with COVID-19 severity

The coronavirus disease 2019 (COVID-19) can evolve to clinical manifestations resembling systemic autoimmune diseases, with the presence of autoantibodies that are still poorly characterized. To address this issue, we performed a cross-sectional study of 246 individuals to determine whether autoantibodies targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS)-related molecules were associated with COVID-19-related clinical outcomes. Moderate and severe patients exhibited the highest autoantibody levels, relative to both healthy controls and patients with mild COVID-19 symptoms. Random Forest, a machine learning model, ranked anti-GPCR autoantibodies targeting downstream molecules in the RAS signaling pathway such as the angiotensin II type 1 and Mas receptor, and the chemokine receptor CXCR3 as the three strongest predictors of severe disease. Moreover, while the autoantibody network signatures were relatively conserved in patients with mild COVID-19 compared to healthy controls, they were disrupted in moderate and most perturbed in severe patients. Our data indicate that the relationship between autoantibodies targeting GPCRs and RAS-related molecules associates with the clinical severity of COVID-19, suggesting novel molecular pathways for therapeutic interventions.

Trends in accident-related admissions to pediatric intensive care units during the first COVID-19 lockdown in Germany

ObjectiveTo compare the number of accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID-19 lockdown with previous years. To investigate if shifts in types of accidents or injuries occurred, especially regarding non-accidental injuries. DesignRetrospective observational multicenter study. Setting37 German PICUs. Patients1444 children and adolescents < 18 years admitted to German PICUs due to trauma or injuries during the first German lockdown period (16.3.-31.5.2020) and during the same periods of the years 2017-2019. InterventionsNone. Measurements and main resultsStandardized morbidity ratios (SMR) and 95% confidence intervals (CI) were calculated for the severity of disease, admission reasons, types of accidents, injury patterns, surgeries and procedures, and outcomes. Disease severity did not differ from previous years. We found an increase in ingestions (SMR 1.41 (CI 0.88 - 2.16)) and a decrease in aspirations (0.77 (0.41 - 1.32)) and burns (0.82 (0.59 - 1.12)). The total number of admissions for trauma remained constant, but traffic accidents (0.76 (0.56 - 1.01) and school/kindergarten accidents (0.25 (0.05 - 0.74) decreased. Household (1.32 (1.05 - 1.64)) and leisure accidents (1.32 (1.05 - 1.65)) increased. Injured structures did not change, but less neurosurgeries (0.69 (0.42 - 1.07)) and more visceral surgeries (2.00 (1.14 - 3.24)) were performed. Non-accidental non-suicidal injuries declined (0.85 (0.50 - 1.37)). Suicide attempts increased in adolescent boys (1.57 (0.58 - 3.42)), while there was a decrease in adolescent girls (0.86 (0.53 - 1.31)). ConclusionsOur study showed shifts in trauma types and associated surgeries during the lockdown period that are generally in line with current literature. The decreased number of non-accidental non-suicidal injuries we observed does not suggest a fundamental increase in severe child abuse during the lockdown period. The decrease in suicide attempts among adolescent girls confirms previous findings, while the increase among boys has not been described yet and deserves further investigation.