The cGAS–STING pathway drives type I IFN immunopathology in COVID-19 DOI Creative Commons
Jérémy Di Domizio, Muhammet F. Gülen, Fanny Saidoune

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7899), P. 145 - 151

Published: Jan. 19, 2022

Abstract COVID-19, which is caused by infection with SARS-CoV-2, characterized lung pathology and extrapulmonary complications 1,2 . Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs 3–5 ). Although rapid induction type IFNs limits virus propagation, a sustained increase levels late phase associated aberrant inflammation poor clinical outcome 5–17 Here we show that cyclic GMP-AMP synthase (cGAS)–stimulator interferon genes (STING) pathway, controls immunity to cytosolic DNA, critical driver IFN responses (ref. 18 Profiling skin manifestations, uncover STING-dependent signature primarily mediated macrophages adjacent areas endothelial cell damage. Moreover, cGAS–STING activity was detected samples from patients prominent tissue destruction, responses. A lung-on-chip model revealed that, addition macrophages, SARS-CoV-2 activates signalling cells through mitochondrial DNA release, leads death production. In mice, pharmacological inhibition STING reduces severe induced improves disease outcome. Collectively, our study establishes mechanistic basis pathological reveals principle for development host-directed therapeutics.

Language: Английский

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection DOI Creative Commons
Jennifer M. Dan, José Mateus, Yu Kato

et al.

Science, Journal Year: 2021, Volume and Issue: 371(6529)

Published: Jan. 6, 2021

Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines assessing the likely future course of COVID-19 pandemic. We analyzed multiple compartments circulating SARS-CoV-2 in 254 samples from 188 cases, including 43 at ≥6 months after infection. Immunoglobulin G (IgG) spike protein was relatively stable over 6+ months. Spike-specific B cells were more abundant 6 than 1 month symptom onset. SARS-CoV-2-specific CD4

Language: Английский

Citations

2747
Cytokine Storm DOI Open Access
David C. Fajgenbaum, Carl H. June

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(23), P. 2255 - 2273

Published: Dec. 2, 2020

Common Terminology Criteria for Adverse

Language: Английский

Citations

2531
Autoantibodies against type I IFNs in patients with life-threatening COVID-19 DOI Creative Commons
Paul Bastard, Lindsey B. Rosen, Qian Zhang

et al.

Science, Journal Year: 2020, Volume and Issue: 370(6515)

Published: Sept. 24, 2020

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block SARS-CoV-2 vitro. These were not found 663 individuals asymptomatic mild and present only 4 1227 healthy individuals. Patients aged 25 87 years 95 men. A B cell autoimmune phenocopy inborn errors IFN immunity accounts for COVID-19 2.6% women 12.5%

Language: Английский

Citations

2508
Adaptive immunity to SARS-CoV-2 and COVID-19 DOI Creative Commons
Alessandro Sette, Shane Crotty

Cell, Journal Year: 2021, Volume and Issue: 184(4), P. 861 - 880

Published: Jan. 13, 2021

Language: Английский

Citations

1792
Genetic mechanisms of critical illness in COVID-19 DOI Creative Commons
Erola Pairo‐Castineira, Sara Clohisey, Lucija Klarić

et al.

Nature, Journal Year: 2020, Volume and Issue: 591(7848), P. 92 - 98

Published: Dec. 11, 2020

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with may identify mechanistic targets for therapeutic development3. Here we report results of GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study 2,244 critically ill patients COVID-19 from 208 UK intensive care units. We have identified replicated following new significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 OAS3); 19p13.2 (rs74956615, 2.3 near tyrosine kinase 2 (TYK2); 19p13.3 (rs2109069, 3.98 10-12) within dipeptidyl peptidase 9 (DPP9); 21q22.1 (rs2236757, 4.99 interferon receptor IFNAR2. potential repurposing licensed medications: using Mendelian randomization, found evidence low expression IFNAR2, or high TYK2, are life-threatening disease; transcriptome-wide tissue revealed monocyte-macrophage chemotactic CCR2 severe COVID-19. Our robust signals relating to key host defence mechanisms mediators inflammatory organ damage Both be amenable targeted treatment existing drugs. However, large-scale randomized clinical trials will essential before any change practice.

Language: Английский

Citations

1369
Risk factors for severe and critically ill COVID‐19 patients: A review DOI Creative Commons
Yadong Gao, Mei Ding, Xiang Dong

et al.

Allergy, Journal Year: 2020, Volume and Issue: 76(2), P. 428 - 455

Published: Nov. 13, 2020

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), has an unprecedented global social and economic impact, high numbers deaths. Many risk factors have been identified in progression COVID-19 into a critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver kidney tumors, clinically apparent immunodeficiencies, local early type I interferon secretion capacity, pregnancy. Possible complications include injury, coagulation disorders, thoromboembolism. development lymphopenia eosinopenia are laboratory indicators COVID-19. Laboratory parameters to monitor lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), ferritin. cytokine storm extensive chest computed tomography imaging patterns disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day initiation treatment, quality health care reported influence individual outcomes. this review, we highlight scientific evidence on severity

Language: Английский

Citations

1307
The T cell immune response against SARS-CoV-2 DOI Open Access
Paul Moss

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 186 - 193

Published: Feb. 1, 2022

Language: Английский

Citations

1110
COVID-19 and diabetes mellitus: from pathophysiology to clinical management DOI Creative Commons
Soo Lim, Jae Hyun Bae, Hyuk‐Sang Kwon

et al.

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 17(1), P. 11 - 30

Published: Nov. 13, 2020

Language: Английский

Citations

936
Mapping the human genetic architecture of COVID-19 DOI Creative Commons
Mari Niemi, Juha Karjalainen, Rachel G. Liao

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7889), P. 472 - 477

Published: July 8, 2021

The genetic make-up of an individual contributes to the susceptibility and response viral infection. Although environmental, clinical social factors have a role in chance exposure SARS-CoV-2 severity COVID-191,2, host genetics may also be important. Identifying host-specific reveal biological mechanisms therapeutic relevance clarify causal relationships modifiable environmental risk for infection outcomes. We formed global network researchers investigate human COVID-19 severity. Here we describe results three genome-wide association meta-analyses that consist up 49,562 patients with from 46 studies across 19 countries. report 13 significant loci are associated or severe manifestations COVID-19. Several these correspond previously documented associations lung autoimmune inflammatory diseases3-7. They represent potentially actionable Mendelian randomization analyses support smoking body-mass index although not type II diabetes. identification novel was made possible by community coming together prioritize sharing data, results, resources analytical frameworks. This working model international collaboration underscores what is future discoveries emerging pandemics, indeed any complex disease.

Language: Английский

Citations

876
Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee DOI Creative Commons
Stuart G. Tangye, Waleed Al–Herz,

Aziz Bousfiha

et al.

Journal of Clinical Immunology, Journal Year: 2022, Volume and Issue: 42(7), P. 1473 - 1507

Published: June 24, 2022

Abstract We report the updated classification of inborn errors immunity, compiled by International Union Immunological Societies Expert Committee. This documents key clinical and laboratory features 55 novel monogenic gene defects, 1 phenocopy due to autoantibodies, that have either been discovered since previous update (published January 2020) or were characterized earlier but confirmed expanded in subsequent studies. While variants additional genes associated with immune diseases reported literature, this includes only those committee assessed reached necessary threshold represent immunity. There are now a total 485 These advances discovering genetic causes human continue significantly further our understanding molecular, cellular, immunological mechanisms disease pathogenesis, thereby simultaneously enhancing knowledge improving patient diagnosis management. is designed serve as resource for immunologists geneticists pursuing molecular individuals heritable disorders scientific dissection cellular underlying related diseases.

Language: Английский

Citations

846