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.

Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

Some clusters of children with a multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C) have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

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Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that: 1) MIS-C and pre-pandemic KD cytokine profiles may be unique and justify the clinical differences observed; 2) SARS-CoV-2-specific immune complexes (IC) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 MIS-C; 9 patients with positive SARS-CoV-2-PCR without MIS-C (COVID); 14 pre-pandemic KD and 37 healthy controls (HC). Thirty-four circulating cytokines were quantified in pre-treatment serum or plasma samples and the presence of circulating SARS-CoV-2 IC was evaluated in MIS-C patients.Compared to HC, MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, IP-10) and inflammatory monocytes activation markers (including MCP-1, IL-1α, IL-1RA) being the main triggers of inflammation. With linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-C plus ) differentiated from the remaining MIS-C patients in IFNγ, IL-18, GM-CSF, RANTES, IP-10, IL-1α and SDF-1 and incipient signs of macrophagic activation syndrome. Circulating SARS-CoV-2-IC were not detected in MIS-C patients. Our findings suggest a major role of IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.

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.

This study aimed to investigate whether using lung ultrasound (LUS) scores in premature newborns with respiratory distress syndrome (RDS) allows for earlier surfactant therapy (within the first 3 h of life) than using FiO 2 criteria. This was a randomised, non-blinded clinical trial conducted in a neonatal intensive care unit. The inclusion criteria were newborns with a gestational age of ≤ 32 weeks and RDS. Patients meeting the inclusion criteria were randomly assigned to two groups: the ultrasound group, administered surfactant based on LUS score and/or FiO 2 threshold, and the control group, guided by FiO 2 only. Fifty-six patients were included. The ultrasound group received surfactant earlier (1 h of life vs. 6 h, p < 0.001), with lower FiO 2 (25% vs. 30%, p = 0.016) and lower CO 2 (48 vs. 54, p = 0.011). After surfactant treatment, newborns in the ultrasound group presented a greater SpO 2 (p = 0.001) and SpO 2 /FiO 2 ratio (p = 0.012). Conclusions: LUS score allowed an earlier surfactant therapy, reduced oxygen exposure early in life and a better oxygenation after the treatment. This early surfactant replacement may lead to reduced oxygen exposure. Keywords Lung ultrasound. Respiratory distress syndrome. Premature newborns. Surfactant Abbreviations CXR Chest X-ray GA Gestational age LUS Lung ultrasound NA Neonatologist-assistant nCPAP Nasal continuous positive airway pressure What is Known: • Lung ultrasound scores predict the need for surfactant therapy in premature newborns. What is New: • This study shows that using lung ultrasound scores improves the timeliness of surfactant replacement compared with using FiO 2 alone.