- 作者: Alain C. Borczuk & Rhonda K. Yantiss
- 作者服務機構: 1.Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 525 East 68th Street, New York, NY, 10065, USA 2.Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Greenvale, NY, USA
- 中文摘要:
- 英文摘要:
Severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) is the causal agent of coronavirus disease-2019 (COVID-19), a systemic illness characterized by variably severe pulmonary symptoms, cardiac conduction
abnormalities, diarrhea, and gastrointestinal bleeding, as well as neurologic defcits, renal insufciency, myalgias,
endocrine abnormalities, and other perturbations that refect widespread microvascular injury and a pro-infammatory state. The mechanisms underlying the various manifestations of viral infection are incompletely understood but
most data suggest that severe COVID-19 results from virus-driven perturbations in the immune system and resultant
tissue injury. Aberrant interferon-related responses lead to alterations in cytokine elaboration that deplete resident
immune cells while simultaneously recruiting hyperactive macrophages and functionally altered neutrophils, thereby
tipping the balance from adaptive immunity to innate immunity. Disproportionate activation of these macrophages
and neutrophils further depletes normal activity of B-cells, T-cells, and natural killer (NK) cells. In addition, this proinfammatory state stimulates uncontrolled complement activation and development of neutrophil extracellular traps
(NETS), both of which promote the coagulation cascade and induce a state of “thrombo-infammation”. These perturbations have similar manifestations in multiple organ systems, which frequently show pathologic fndings related
to microvascular injury and thrombosis of large and small vessels. However, the pulmonary fndings in patients with
severe COVID-19 are generally more pronounced than those of other organs. Not only do they feature infammatory
thromboses and endothelial injury, but much of the parenchymal damage stems from failed maturation of alveolar
pneumocytes, interactions between type 2 pneumocytes and non-resident macrophages, and a greater degree of
NET formation. The purpose of this review is to discuss the pathogenesis underlying organ damage that can occur in
patients with SARS-CoV-2 infection. Understanding these mechanisms of injury is important to development of future
therapies for patients with COVID-19, many of which will likely target specifc components of the immune system,
particularly NET induction, pro-infammatory cytokines, and subpopulations of immune cells. - 中文關鍵字:
- 英文關鍵字: COVID-19, SARS-CoV-2, Pathology, Histology, Mechanisms