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.

Background The main purpose in this study carried out from the perspective of infodemic was to investigate the relationships between individuals’ perceived causes of COVID-19, their attitudes towards vaccine and their levels of trust in information sources in terms of various descriptive characteristics. Methods In this cross-sectional and correlational study conducted with 1216 individuals from different provinces of Turkey, the Perception of Causes of COVID-19 (PCa-COVID-19) Scale was used. In addition, a questionnaire including the participants’ descriptive characteristics, their attitudes towards vaccine and their level of trust in information sources about Covid-19 was used. Results The mean age of the participants was 35.9 ± 12.3 years. Of them, 62.5% were women, 59.0% were married, and 62.1% were university graduates. As for their view of having the Covid-19 vaccine, 54.1% thought to have it, 16.2% did not think, and 29.7% were undecided. Although the correlation was not significant, of the participants, those who considered having vaccination mostly trusted YouTube as their source of information. Of the participants, those whose level of trust in government institutions and health professionals was high displayed significantly more favorable attitudes towards vaccine. The participants obtained the highest mean score from the Conspiracy Theories subscale of the PCa-COVID-19 scale. There was a positive and low-level relationship between attitudes towards COVID-19 vaccine, and the Conspiracy Theories (r: 0.214) and Faith Factors (r: 0.066) sub-dimensions of the PCa-COVID-19 Scale. Conclusions The level of vaccine hesitancy in Turkey is at an alarming level, and the virus is defined by moderate conspiracy theories. In this context, in the fight against infodemic, it is critical to implement mechanisms that can reveal misinformation and to plan initiatives that can increase the health literacy levels of societies.

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Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.

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