Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted on mink farms between minks and humans in many countries. However, the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown. Here, we demonstrated that minks were largely permissive to SARS-CoV-2, characterized by severe and diffuse alveolar damage, and lasted at least 14 days post inoculation (dpi). We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular, hepatobiliary, urinary, endocrine, digestive, and immune systems. The viral protein partially co-localized with activated Mac-2 + macrophages throughout the body. Moreover, we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks, especially at 6 dpi, and were similar to that of patients with severe and fatal COVID-19. Particularly, altered metabolic pathways, abnormal digestion, and absorption of vitamins, lipids, cholesterol, steroids, amino acids, and proteins, consistent with hepatic dysfunction, highlight metabolic and immune dysregulation. Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation. Melatonin, which has significant anti-inflammatory and immunomodulating effects, was significantly downregulated at 6 dpi and displayed potential as a targeted medicine. Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients, delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies, vaccine research, and potential biomarkers.
【저자키워드】 Infectious diseases, Infection, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Macrophage, Vaccine, coronavirus, macrophages, melatonin, Anti-inflammatory, Human, animal model, Proteins, severe acute respiratory syndrome Coronavirus, Steroids, vitamins, Viral, inoculation, Research, Patient, amino acids, Kynurenine, Diffuse alveolar damage, cholesterol, metabolites, respiratory, lipids, distribution, macrophage activation, metabolite, COVID-19 patients, Kynurenine pathway, Inflammatory response, Lipid, Endocrine, metabolic pathways, immune dysregulation, digestion, dysregulation, alveolar damage, hepatic dysfunction, observation, lesion, acute respiratory syndrome, Activation, Treatment strategies, Viral protein, acute respiratory syndrome coronavirus, alteration, potential biomarkers, Absorption, fatal COVID-19, immune systems, immunomodulating, widespread, Effects, feature, effective, highlight, post inoculation, significantly, reported, transmitted, characterized, activated, demonstrated, analysis, correlated, digestive, contributed, downregulated, fetal, histological, accompanied, pathophysiological feature, was related, 【제목키워드】 animal model, pathogenicity, profile, metabolomic, histopathological, severe COVID-19 patient,