Innate immunological pathways in COVID-19 pathogenesis

Science Immunology, Год журнала: 2022, Номер 7(67)

Опубликована: Янв. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Язык: 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, Год журнала: 2022, Номер 119(21)

Опубликована: Май 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.

Язык: Английский

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The humoral response and antibodies against SARS-CoV-2 infection

Nature Immunology, Год журнала: 2022, Номер 23(7), С. 1008 - 1020

Опубликована: Июнь 27, 2022

Язык: Английский

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Autoimmunity is a hallmark of post-COVID syndrome

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Март 16, 2022

Abstract Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order further investigate relationship between SARS-CoV-2 and autoimmunity in PCS, clinical serological assessment on 100 patients was done. Serum antibody profiles against self-antigens infectious agents were evaluated by an antigen array chip for 116 IgG 104 IgM antibodies. Thirty pre-pandemic healthy individuals included control group. The median age 49 years (IQR: 37.8 55.3). There 47 males. time 219 143 258) days. Latent polyautoimmunity found 83% 62% patients, respectively. Three developed overt autoimmune disease. antibodies IL-2, CD8B, thyroglobulin more than 10% patients. Other autoantibodies, such anti-interferons, positive 5–10% Anti-SARS-CoV-2 > 85% positively correlated with age, body mass index (BMI). Few autoantibodies influenced BMI. no effect gender over- or under-expression autoantibodies. anti-IFN-λ associated persistence respiratory symptoms. summary, is latent correlates humoral response SARS-CoV-2.

Язык: Английский

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The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

Nature reviews. Immunology, Год журнала: 2022, Номер 23(5), С. 304 - 316

Опубликована: Дек. 20, 2022

Язык: Английский

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Mechanisms of viral inflammation and disease in humans

Science, Год журнала: 2021, Номер 374(6571), С. 1080 - 1086

Опубликована: Ноя. 25, 2021

Disease and accompanying inflammation are uncommon outcomes of viral infection in humans. Clinical occurs if steady-state cell-intrinsic leukocytic immunity to viruses fails. Inflammation attests the attempts newly recruited activated leukocytes resolve blood or tissues. In confusing battle between a myriad cells, studies human genetics can separate root cause disease from its consequences. Single-gene inborn errors underlying diverse infections skin, brain, lungs help clarify determinants disease. The genetic elucidation immunological deficits single patient with specific vulnerability profile reveal mechanisms that may be triggered by other causes, inherited otherwise, patients. This dissection is giving rise new biology medicine.

Язык: Английский

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

Science, Год журнала: 2022, Номер 379(6632)

Опубликована: Дек. 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

Язык: Английский

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The human genetic epidemiology of COVID-19

Nature Reviews Genetics, Год журнала: 2022, Номер 23(9), С. 533 - 546

Опубликована: Май 2, 2022

Язык: Английский

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Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Март 9, 2022

Abstract COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand role these immune globulins in pathogenesis disease, it is important explore spectra. Here we show, by a cross-sectional study 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate clinical severity COVID-19. Patients moderate severe disease are characterized higher levels than healthy controls those mild disease. Among anti-GPCR autoantibodies, machine learning classification identifies chemokine receptor CXCR3 molecule AGTR1 as targets for antibodies strongest association severity. Besides antibody levels, network signatures also changing patients intermediate or high Although our current previous studies identify natural components human biology, their deregulated level pattern alterations might predict

Язык: Английский

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The intersection of COVID-19 and autoimmunity

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(24)

Опубликована: Окт. 28, 2021

Acute COVID-19, caused by SARS-CoV-2, is characterized diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute pathogenesis of severe COVID-19. Researchers working at intersection COVID-19 autoimmunity recently gathered an American Autoimmune Related Diseases Association Noel R. Rose Colloquium address current state knowledge regarding two important questions: Does established predispose COVID-19? And, same time, can SARS-CoV-2 trigger de novo autoimmunity? Indeed, work date demonstrated 10% 15% patients critical pneumonia exhibit autoantibodies against type I interferons, suggesting preexisting underlies disease in some patients. Other studies have identified functional following such as those promote thrombosis or antagonize cytokine signaling. These may arise a predominantly extrafollicular B cell response more prone generating autoantibody-secreting cells. This Review highlights understanding, evolving concepts, unanswered questions provided this unique opportunity determine mechanisms which viral be exacerbated by, even trigger, autoimmunity. The potential role post-acute sequelae also discussed.

Язык: Английский

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