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Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins in inflamed tissue and on the endothelium during COVID-19. Using a transgenic mouse model of SARS-CoV-2 infection, we assessed the therapeutic utility of an inhibitory antibody (HG4) targeting MASP-2, a key enzyme in the lectin pathway. Treatment of infected mice with HG4 reduced the disease severity score and improved survival vs mice that received an isotype control antibody. Administration of HG4 significantly reduced the lung injury score, including alveolar inflammatory cell infiltration, alveolar edema, and alveolar hemorrhage. The ameliorating effect of MASP-2 inhibition on the severity of COVID-19 pathology is reflected by a significant reduction in the proinflammatory activation of brain microglia in HG4-treated mice.<\/jats:p>","DOI":"10.1093\/infdis\/jiad462","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T18:30:56Z","timestamp":1698258656000},"page":"680-690","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of the Lectin Pathway of Complement Activation Reduces Acute Respiratory Distress Syndrome Severity in a Mouse Model of SARS-CoV-2 Infection"],"prefix":"10.1093","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-9848","authenticated-orcid":false,"given":"Youssif M","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge , Cambridge CB3 0ES , UK"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura 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