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.

Objectives This study aimed to evaluate patient satisfaction and oral health‐related quality of life (OHRQoL) of conventional denture, fixed prosthesis and milled bar overdenture for All‐on‐4 implant rehabilitation. Materials and methods Sixteen completely edentulous patients with ill‐fitted mandibular dentures received new mandibular dentures (CDs). After 3 months, 4 implants were installed according to the “All‐on‐4 concept” and immediately loaded with mandibular dentures. Three months after osseointegration, patients received either fixed prosthesis (FP) or milled bar overdenture (MB) in a crossover design. Patient satisfaction was evaluated using a visual analog scale (VAS). OHRQoL was evaluated using the OHIP‐14. Questionnaires of VAS and OHIP‐14 were measured 3 months after wearing each of the following prostheses: CD, FP, and MB. Results For all questions of VAS and OHIP‐14, CD showed significant lower satisfaction compared to FP and MB (p < .00025). FP recorded significant higher VAS scores than MB regarding retention and stability (p < .00007). MB recorded significant higher scores than FP regarding general satisfaction, comfort, ease of cleaning, and handling (p < .00008). Regarding OHIP‐14, no significant differences in OHIP scores between FP and MB were observed for all domains of OHIP. Conclusion “All‐on‐4” implant rehabilitation of edentulous mandible with FP and MB achieves high patient satisfaction and OHRQoL compared to CD. No significant difference in OHRQoL between FP and MB was observed. Regarding VAS, FP rated greater satisfaction with retention, stability, and chewing compared to MB. However, MB rated greater satisfaction with ease of cleaning and handling compared to FP.

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