Comparative Histology and Proteome Analysis of Human and Mink Sars-Cov-2 Infected Lung Tissue

Abstract

Objectives COVID-19 pneumonia caused by SARS-CoV-2 in humans and minks shows similar diffuse alveolar damage (DAD) in lung tissue, though (micro)thrombi, common in humans, are rare in minks. Design Histopathologic and proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) lung tissue obtained from autopsies of 20 humans and 45 minks naturally infected with SARS-CoV-2. Humans succumbed to COVID-19 and minks either died of COVID-19 or were euthanized due to culling. Results Histology showed signs of diffuse alveolar damage (DAD) in both species, minks however showed fewer thrombi and no pulmonary fibrosis. LC-MS analysis of lung tissue samples identified upregulated coagulation and inflammation pathways in both species, including thrombin, integrin, VEGF, neutrophil extracellular traps, and interleukins (IL-6, IL-8, IL-12, IL-17A, IL-33). Upregulation of intrinsic prothrombin activation pathway in humans and PDGF signaling in minks implies vascular damage in both species. Conclusion These findings suggest vascular damage may play a role in COVID-19 pathogenesis in both species, despite less thrombi and fibrosis in lung tissue of minks. Overall, the proteomic pathways were similar between humans and minks, highlighting minks as a potential model for studying SARS-CoV-2 kinetics and immunopathology.

Note:
Funding declaration: The Netherlands Organization for Health Research and Development (ZonMw), Grant/Award Number: 10430012010016.

Conflict of Interests: All authors declare that they have no conflicts of interest.

Ethical Approval: Consent was provided by the next of kin to utilize post-mortem organ tissue from human autopsies for research purposes. Permission for utilization of human COVID-19 tissue samples was granted by the Medical Ethics Review Committee (MEC-2020-0322).

Keywords: SARS-CoV-2, histology, proteomics, Thrombosis, comparative pathology, mink, human