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The interplay between neutrophils, complement, and microthrombi in COVID-19.

ABSTRACT: As of the end of 2020, coronavirus disease 2019 (COVID-19) remains a global healthcare challenge with alarming death tolls. In the absence of targeted therapies, supportive care continues to be the mainstay of treatment. The hallmark of severe COVID-19 is a thromboinflammatory storm driven by innate immune responses. This manifests clinically as acute respiratory distress syndrome, and in some patients, widespread thrombotic microangiopathy. Neutrophils and complement are key players in the innate immune system, and their role in perpetuating fatal severe COVID-19 continues to receive increasing attention. Here, we review the interplay between neutrophils, neutrophil extracellular traps, and complement in COVID-19 immunopathology, and highlight potential therapeutic strategies to combat these pathways.

SUBMITTER: Zuo Y

PROVIDER: S-EPMC7831864 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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The interplay between neutrophils, complement, and microthrombi in COVID-19.

Zuo Yu Y Kanthi Yogendra Y Knight Jason S JS Kim Alfred H J AHJ

Best practice & research. Clinical rheumatology 20210113 1

As of the end of 2020, coronavirus disease 2019 (COVID-19) remains a global healthcare challenge with alarming death tolls. In the absence of targeted therapies, supportive care continues to be the mainstay of treatment. The hallmark of severe COVID-19 is a thromboinflammatory storm driven by innate immune responses. This manifests clinically as acute respiratory distress syndrome, and in some patients, widespread thrombotic microangiopathy. Neutrophils and complement are key players in the inna ...[more]

PMID: 33526325

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.MethodsStudy cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.ResultsMale sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.ConclusionsThis detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

Project description:Coronavirus Disease 2019 (COVID-19), a disease caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has only recently emerged, while Mycobacterium leprae, the etiological agent of leprosy, has endured for more than 2,000 years. As soon as the initial reports of COVID-19 became public, several entities, including the Brazilian Leprosy Society, warned about the possible impact of COVID-19 on leprosy patients. It has been verified that COVID-19 carriers can be either asymptomatic or present varying degrees of severe respiratory failure in association with cytokine storm and death, among other diseases. Severe COVID-19 patients show increased numbers of neutrophils and serum neutrophil extracellular trap (NET) markers, in addition to alterations in the neutrophil-to-lymphocyte ratio (NLR). The absence of antiviral drugs and the speed of COVID-19 transmission have had a major impact on public health systems worldwide, leading to the almost total collapse of many national and local healthcare services. Leprosy, an infectious neurological and dermatological illness, is widely considered to be the most frequent cause of physical disabilities globally. The chronic clinical course of the disease may be interrupted by acute inflammatory episodes, named leprosy reactions. These serious immunological complications, characterized by cytokine storms, are responsible for amplifying peripheral nerve damage. From 30% to 40% of all multibacillary leprosy (MB) patients experience erythema nodosum leprosum (ENL), a neutrophilic immune-mediated condition. ENL patients often present these same COVID-19-like symptoms, including high levels of serum NET markers, altered NLR, and neutrophilia. Moreover, the consequences of a M. leprae-SARS-CoV-2 coinfection have yet to be fully investigated. The goal of the present viewpoint is to describe some of the similarities that may be found between COVID-19 and leprosy disease in the context of neutrophilic biology.

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The interplay between neutrophils, complement, and microthrombi in COVID-19.

Publications

The interplay between neutrophils, complement, and microthrombi in COVID-19.

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