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Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets.

ABSTRACT: Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.

SUBMITTER: Hazeldine J

PROVIDER: S-EPMC8206563 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren's syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still's disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.Key Points• Patients with coronavirus disease 19 (COVID-19) may have features mimicking rheumatic diseases, such as arthralgias, acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.

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Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets.

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