Multiple early factors anticipate post-acute COVID-19 sequelae

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 881 - 895.e20

Published: Jan. 25, 2022

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation 309 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data patient-reported symptoms. resolved four PASC-anticipating at the time diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, specific auto-antibodies. In gastrointestinal PASC, SARS-CoV-2-specific CMV-specific CD8+ T cells exhibited unique dynamics during recovery COVID-19. Analysis symptom-associated immunological signatures revealed coordinated immunity polarization into endotypes, exhibiting divergent acute severity PASC. find that between diminish over time, leading distinct convalescent immune states. Detectability most emphasizes importance early disease measurements understanding emergent chronic conditions suggests treatment strategies.

Language: Английский

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Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

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

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SARS-CoV-2 pathogenesis

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

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Innate immunity: the first line of defense against SARS-CoV-2

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 165 - 176

Published: Feb. 1, 2022

Language: Английский

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X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Science Immunology, Journal Year: 2021, Volume and Issue: 6(62)

Published: Aug. 10, 2021

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort 1,202 patients 0.5 99 52.9 with unexplained pneumonia. None the 331 asymptomatically or mildly infected 1.3 102 38.7 tested carry such (p = 3.5 × 10-5). The phenotypes five hemizygous relatives index cases SARS-CoV-2 include asymptomatic mild infection (n=2, 5 38 years), moderate (n=1, severe 27 29 Two boys (aged 12 262 51.0 are for variant. cumulative allele frequency general population is < 6.5x10-4 also show that blood B cell lines myeloid subsets do not respond stimulation, phenotype rescued by wild-type patients' plasmacytoid dendritic cells (pDCs) produce low levels IFNs response SARS-CoV-2. Overall, recessive deficiency highly penetrant genetic etiology pneumonia, about 1.8% below age 60 years. Human pDCs essential protective respiratory tract.

Language: Английский

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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 IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(6), P. 100663 - 100663

Published: June 1, 2022

Language: Английский

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Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

Medicina, Journal Year: 2022, Volume and Issue: 58(2), P. 144 - 144

Published: Jan. 18, 2022

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated multi-organ failure and coagulopathy, leading, in most severe cases, even death. The term was first used 1993 describe graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. then reused define adverse syndromes administration immunostimulating agents, such anti-CD28 antibodies or bioengineered cells, i.e., CAR T-cell therapy. Currently, concept has been better elucidated extended pathogenesis many other conditions, sepsis, autoinflammatory disease, primary hemophagocytic lymphohistiocytosis, multicentric Castleman disease. Moreover, recently emerged key aspect novel Coronavirus 2019, affected patients show high levels several pro-inflammatory cytokines, IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, IL-10, some also correlate with severity. Therefore, since onset pandemic, numerous agents have tested effort mitigate COVID-19 patients, are effective reducing mortality, especially critically ill now becoming standards care, glucocorticoids inhibitors. However, challenge still far from being met, therapeutic strategies hope that we eventually overcome

Language: Английский

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Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(612)

Published: Aug. 24, 2021

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the caused by severe acute respiratory syndrome 2 (SARS-CoV-2). However, prevalence of these antibodies, their longitudinal dynamics across severity scale, and functional effects on circulating leukocytes remain unknown. Here, 284 COVID-19, we IFN–specific peripheral blood samples from 19% 6% disease. We no IFN individuals moderate Longitudinal profiling over 600,000 mononuclear cells using multiplexed single-cell epitope transcriptome sequencing 54 COVID-19 26 non–COVID-19 controls revealed a lack IFN–stimulated gene (ISG-I) responses myeloid This was especially evident dendritic cell populations isolated producing autoantibodies. Moreover, elevated expression inhibitory receptor leukocyte-associated immunoglobulin-like 1 (LAIR1) surface monocytes early course. LAIR1 is inversely correlated ISG-I response but not expressed healthy controls. The deficient observed without supports unifying model for pathogenesis involving suppression through convergent mechanisms.

Language: Английский

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Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(5), P. 1050 - 1062

Published: Feb. 17, 2022

Language: Английский

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