Human genetic and immunological determinants of critical COVID-19 pneumonia

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 587 - 598

Published: Jan. 28, 2022

Language: Английский

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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(21)

Published: May 16, 2022

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased infection fatality rate at all ages, men women. Autoantibodies common predictors COVID-19. Testing for should be considered population.

Language: Английский

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COVID-19 2022 update: transition of the pandemic to the endemic phase

Human Genomics, Journal Year: 2022, Volume and Issue: 16(1)

Published: June 1, 2022

Abstract COVID-19, which is caused by the SARS-CoV-2, has ravaged world for past 2 years. Here, we review current state of research into disease with focus on its history, human genetics and genomics transition from pandemic to endemic phase. We are particularly concerned lack solid information initial phases that highlighted necessity better preparation face similar future threats. On other hand, gratified progress genetic susceptibility investigations believe now time explore The latter will require worldwide vigilance cooperation, especially in emerging countries. In phase, vaccination rates have lagged developed countries should assist, as warranted, bolstering worldwide. also discuss status vaccines outlook COVID-19.

Language: Английский

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Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children

Science, Journal Year: 2022, Volume and Issue: 379(6632)

Published: Dec. 20, 2022

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 or RNASEL five unrelated with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing generate 2′-5′-linked oligoadenylates (2-5A) activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines primary myeloid cells OAS1, OAS2, RNase produce excessive amounts cytokines upon dsRNA acute respiratory coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production OAS1-deficient but not L–deficient cells. Cytokine impaired by MDA5 RIG-I deficiency abolished mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase these patients unleash SARS-CoV-2–triggered, MAVS-mediated mononuclear phagocytes, thereby underlying

Language: Английский

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From rare disorders of immunity to common determinants of infection: Following the mechanistic thread

Cell, Journal Year: 2022, Volume and Issue: 185(17), P. 3086 - 3103

Published: Aug. 1, 2022

The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria seasonal influenza virus have inspired studies two common infections: tuberculosis COVID-19. A TYK2 genotype impairing production accounts for about 1% cases, autoantibodies neutralizing account 15% critical COVID-19 cases. discovery inborn mechanisms drove the identification monogenic or autoimmune determinants related infections. This “rare-to-common” genetic mechanistic approach to infectious diseases may be heuristic value.

Language: Английский

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Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Language: Английский

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Human autoantibodies underlying infectious diseases

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(4)

Published: March 23, 2022

The vast interindividual clinical variability observed in any microbial infection—ranging from silent infection to lethal disease—is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of corresponding cytokine or response pathway. against type I IFNs COVID-19 pneumonia adverse reactions live attenuated yellow fever virus vaccine. II IFN severe disease caused environmental tuberculous mycobacteria, other intra-macrophagic microbes. IL-17A/F IL-6 are less common mucocutaneous candidiasis staphylococcal diseases, respectively. Inborn autoantibodies GM-CSF pulmonary alveolar proteinosis; associated infections well characterized. In individual patients, preexist with pathogen concerned disease. Human antibody-driven autoimmunity can interfere that essential for protective immunity agents but otherwise redundant, thereby underlying diseases.

Language: Английский

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Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(8)

Published: June 16, 2022

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk children, which is much lower than adults, remains unexplained. In an international cohort 112 children (<16 yr old) hospitalized for pneumonia, we report 12 (10.7%) aged 1.5–13 with (7 children), severe (3), and moderate (2) 4 the 15 known clinically recessive biochemically complete IFN immunity: X-linked TLR7 deficiency children) autosomal IFNAR1 (1), STAT2 TYK2 (3) deficiencies. Fibroblasts deficient IFNAR1, STAT2, are highly vulnerable to SARS-CoV-2. These deficiencies were not found 1,224 adults benign SARS-CoV-2 infection without (P = 1.2 × 10−11) overlapping age, sex, consanguinity, ethnicity characteristics. may ∼10% hospitalizations children.

Language: Английский

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Autoantibodies against type I IFNs in patients with critical influenza pneumonia

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(11)

Published: Sept. 16, 2022

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies IFN-α2 alone (five patients) or with IFN-ω (eight from a cohort of 279 (4.7%) aged 6–73 yr influenza pneumonia. Nine four had antibodies high low concentrations, respectively, IFN-α2, six two IFN-ω. The patients’ increased A virus replication in both A549 cells reconstituted human airway epithelia. prevalence these was significantly higher than that the general population for <70 age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not >70 (3.1 4.4%, 0.68). risk highest concentrations (OR 11.7, 1.3 especially those old 139.9, 3.1 10−10). also identified 10 additional patient cohorts. IFNs account ∼5% cases life-threatening old.

Language: Английский

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Naringenin: A flavanone with anti-inflammatory and anti-infective properties

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114990 - 114990

Published: June 12, 2023

Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several the medications currently available on market have various unfavourable side effects, necessitating development alternative therapeutic choices. Researchers increasingly interested in or active components derived from natural sources. Naringenin is commonly consumed flavonoid found many plants, since it was discovered nutritional benefits, been utilized treat infections caused by particular bacteria viruses. However, absence adequate clinical data naringenin's poor solubility stability severely restrict its usage as medicinal agent. In this article, we discuss effects mechanisms action autoimmune-induced inflammation, bacterial infections, viral based recent research. We also present few suggestions for enhancing solubility, stability, bioavailability. This paper emphasizes potential use naringenin an anti-inflammatory anti-infective agent next prophylactic substance treatment inflammatory infectious even though some still unclear, offers theoretical support application.

Language: Английский

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