The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

The Lancet Respiratory Medicine, Год журнала: 2021, Номер 9(6), С. 622 - 642

Опубликована: Май 7, 2021

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into epidemiology of COVID-19, important questions remain about clinical complexities and underlying mechanisms disease phenotypes. Severe most commonly involves respiratory manifestations, although other systems are also affected, acute is often followed by protracted complications. Such complex manifestations suggest dysregulates host response, triggering wide-ranging immuno-inflammatory, thrombotic, parenchymal derangements. We review intricacies pathophysiology, its various phenotypes, anti-SARS-CoV-2 response at humoral cellular levels. Some similarities exist between failure origins, but evidence for many distinctive mechanistic features indicates constitutes a new entity, emerging data suggesting involvement an endotheliopathy-centred pathophysiology. Further research, combining basic studies, needed advance understanding pathophysiological characterise immuno-inflammatory derangements across range phenotypes enable optimum care patients COVID-19.

Язык: Английский

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Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Annals of Neurology, Год журнала: 2021, Номер 89(4), С. 780 - 789

Опубликована: Янв. 22, 2021

This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on severity coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).We retrospectively collected data PwMS suspected or confirmed COVID-19. All patients had complete follow-up death recovery. Severe COVID-19 defined by a 3-level variable: mild not requiring hospitalization versus pneumonia intensive care unit (ICU) admission death. We evaluated baseline characteristics MS associated severe multivariate propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run confirm results.Of 844 (n = 565) 279) COVID-19, 13 (1.54%) died; 11 them progressive phase, 8 without any therapy. Thirty-eight (4.5%) admitted an ICU; 99 (11.7%) radiologically documented pneumonia; 96 (11.4%) hospitalized. After adjusting for region, age, sex, course, Expanded Disability Status Scale, duration, body mass index, comorbidities, recent methylprednisolone use, therapy anti-CD20 agent (ocrelizumab rituximab) significantly (odds ratio [OR] 2.37, 95% confidence interval [CI] 1.18-4.74, p 0.015) increased risk Recent use (<1 month) also worse outcome (OR 5.24, CI 2.20-12.53, 0.001). Results PS-weighted analysis all sensitivity analyses.This showed acceptable level safety broad array mechanisms action. However, some specific elements emerged. These will need be considered while pandemic persists. ANN NEUROL 2021;89:780-789.

Язык: Английский

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Pathophysiology of COVID-19-associated acute kidney injury

Nature Reviews Nephrology, Год журнала: 2021, Номер 17(11), С. 751 - 764

Опубликована: Июль 5, 2021

Язык: Английский

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The cGAS–STING pathway drives type I IFN immunopathology in COVID-19

Nature, Год журнала: 2022, Номер 603(7899), С. 145 - 151

Опубликована: Янв. 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.

Язык: Английский

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The first 12 months of COVID-19: a timeline of immunological insights

Nature reviews. Immunology, Год журнала: 2021, Номер 21(4), С. 245 - 256

Опубликована: Март 15, 2021

Язык: Английский

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