Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription–polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.

Vascular Implications of COVID-19: Role of Radiological Imaging, Artificial Intelligence, and Tissue Characterization: A Special Report

“…In COVID-19, SARS-CoV-2 viral entry results in the downregulation of ACE2 expression and function due to its manner of host cell entry [ 64 ]. Subsequently, reduced ACE2 levels lead to a deficiency of B1R ligand inactivators locally in the lungs, resulting in the activation of BK [ 65 , 66 ]. This might establish a direct link between the virus and pulmonary angioedema by causing vasodilation.…”

Characterization of entry pathways, species-specific ACE2 residues determining entry, and antibody neutralization evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 variants

“…Apart from humans, SARS-CoV-2 was also found to naturally infect diverse domestic and wild animal species, including farm minks 19,20 , companion pets (e.g., cats, dogs, ferrets, Syrian hamsters) [21][22][23] , zoo animals (e.g., lions, tigers, cougars, snow leopards, gorillas, otters, and hippopotami) 24 , and free ranging white-tailed deer 25 . Furthermore, experimental infections in livestock species have determined low-level replication of ancestral variants in cattle 26,27 , pigs 28 , and sheep 27,29 .…”

Special focus on SARS-CoV-2 and other zoonotic respiratory coronaviruses in animal models

“…Numerous publications have been written about the virus, the human disease, diseases found in domestic, zoo, and wild animals, and infection of experimental animals. In Pubmed searches, by early 2022, there were over 2100 publications reporting on experimental infection in mice, over 500 in hamsters, over 300 in nonhuman primates (NHPs), and 200 in ferrets, and more recently, naturally occurring cases in exotic and companion animals including domestic cats and zoo cats, mink, 24 and wild deer. Several of these animal models are reviewed in this issue.…”

“…Diffuse alveolar damage (DAD) is a major often-fatal group of lesions in humans after SARS-CoV, SARS-CoV-2, and influenza infection, but the criteria are not as well described in experimental laboratory animals as they are in domestic animals. 5 Diffuse alveolar damage is usually not a major lesion in SARS-CoV-2-infected animals except in naturally infected mink 24 and experimentally infected Roborovsky hamsters 15 and in some studies with mouse-adapted SARS-CoV-2 virus.…”

“…Other SARS-CoV-2-focused papers in this issue review alternatives to animal models to study SARS-CoV-2 and other respiratory infectious pathogens; 26 influence of SARS-CoV-2 on airway mucus production; 20 SARS-CoV-2 infection in mustelids including ferrets 11 and in experimentally infected cats; 22 and natural SARS-CoV-2 infection in mink, 24 zoo, and companion animals. 25 These papers illustrate the wide species range of SARS-CoV-2 infection and disease, experimental or natural.…”