16 research outputs found
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
SignificanceThere 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
International note: Prevailing with extracurricular activities in an alcohol-dominated environment: Sex differences in resilience among middle school youth
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Rehabilitation Outcomes in Children with Acute Flaccid Myelitis from 2014 to 2019: A Multicenter Retrospective Review
Acute Flaccid Myelitis (AFM) is a childhood illness characterized by sudden onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, neurogenic bowel and bladder in both cohorts.
Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1st, 2014 and October 1st, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits.
Medical records of 109 children met inclusion criteria. 67 children required inpatient rehabilitation while 42 children discharged directly home. The median age was 5 years (range 4 months – 17 years) and median time observed was 417 days (Interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (p<0.001), nutritional support (p<0.001) and neurogenic bowel (p=0.004) and bladder (p=0.002). At follow up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, p=0.043) however nutritional status and bowel/bladder function were no longer statistically different.
All children made improvements in strength whether they discharged home or to inpatient rehabilitation. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow up, however, recovery of nutritional status and bowel/bladder were similar