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.

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Significance There 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.

The Rhône-Loire metropolitan areas’ 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

for the Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) Study Group IMPORTANCE Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED).OBJECTIVE To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis. DESIGN, SETTING, AND PARTICIPANTSThe Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included.INTERVENTIONS Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart. MAIN OUTCOMES AND MEASURESHospital admission rate in the 24 hours after enrollment. RESULTSOf the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, -3.2%; 95% CI, -8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (-3.1 [3.2]) than in the NS group (-2.4 [3.3]) (adjusted difference, -0.7; 95% CI, -1.2 to -0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events.CONCLUSIONS AND RELEVANCE Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01777347

Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is the standard mode of delivery in hospital setting. However, recent guidelines consider spacer devices as an easier to use, and cost-saving alternative and recommend the high-dose metered-dose inhaler bronchodilator. Objective. To demonstrate clinical equivalence between a spacer device and a nebulizer for albuterol administration. Design. Randomized, double-blind, parallel group equivalence trial. Setting. Pediatric emergency wards at 2 tertiary teaching hospitals. Patients. Sixty-four 12- to 60-month-old children with acute recurrent wheezing (32 per group). Interventions. Albuterol was administered through the spacer device (50 μg/kg) or through the nebulizer (150 μg/kg) and repeated 3 times at 20-minute intervals. Parents completed a questionnaire. Outcome Measures. Pulmonary index, hospitalization, ease of use, acceptability, and pulse oximetry saturation. Results. The 90% confidence interval of the difference between treatment groups for the median absolute changes in pulmonary index values between T0 and T60 was [−1; +1] and was included in the equivalence interval [−1.5; +1.5]. Clinical improvement increased with time. Less than 10% of the children (3 in each group) required hospitalization (2 in each group attributable to treatment failure). Parents considered administration of albuterol using the spacer device easier (94%) and better accepted by their children (62%). Conclusions. The efficacy of albuterol administered using the spacer device was equivalent to that of the nebulizer. Given its high tolerance, repeated 50-μg/kg doses of albuterol administered through the spacer device should be considered in hospital emergency departments as first-line therapy for wheezing.

Health outcomes showed that influenza disease burden in young French children is similar to that observed in North America. An active vaccination strategy would have strongly reduced the burden of influenza and lowered antibiotic use. Continuous efforts are needed to reach requirements of our influenza vaccination policy.