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

Coronaviruses (CoVs) cause common diseases of animals and humans.16 In recent decades, zoonotic CoVs that cause severe disease and mortality in humans have been identified. Severe acute respiratory syndrome (SARS) was first reported in 2003 in Asia. The cause was identified as a novel CoV, SARS-CoV, which may have originated from wild animals in a Chinese city food market. Soon thereafter, research on the virus was conducted in laboratory animals throughout the world to study the pathogenesis of the disease, as well as for therapy and prevention research. Fortunately, clinical human disease from SARSCoV disappeared soon thereafter. In 2012, Middle East respiratory syndrome (MERS) was discovered to be caused by a new CoV that infected humans with close contact with dromedary camels in the Middle East but is currently limited as an endemic infection of humans. In late 2019, another CoV infection (COVID-19), caused by SARS-C0V-2, was found in Wuhan, China.21 Within a few months of the first reported infections, it was declared a global pandemic by the World Health Organization (WHO), with widespread human infections and deaths world-wide over the subsequent 2 years. 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. The overwhelming response of the medical community in many countries to a world-wide disease crisis showed the strength of medical research and underscores the paramount importance of adoption of the “One Health” approach to address zoonotic coronaviruses (CoVs) and other global health challenges. Many veterinarians, veterinary pathologists and others in medical research were involved in this massive SARS-CoV-2 research undertaking producing many publications. This special issue of Veterinary Pathology (59[4], July 2022) emphasizes the pathophysiology of respiratory CoV infection from veterinary pathologists and their research colleagues. The field of pathology is critical for infectious disease research from the discovery of disease causes and mechanisms to the development of preventive and therapeutic measures. We include reviews on pathology of specific animal models, in some cases with overlap of content, highlighting areas of consensus and divergent perspectives among pathologists. The various animal models and their applications for study of SARS-CoV-2 infection is reviewed as an introduction to the issue.9 Working with these viruses requires biological safety level-3 (BSL-3) animal and laboratory containment, which presents some challenges, and involves defined safety standards and biosafety protocols for necropsy and tissue handling and storage.4 The histopathology of SARS-CoV-2 infection in mice, hamsters, NHPs, ferrets, and cats has been described by many authors, but there is no uniform histopathology nomenclature for the lung and upper respiratory tract lesions. Investigators either do not provide histopathology scoring or use different criteria for different lesions. Diffuse alveolar damage (DAD) is a major often-fatal group of lesions in humans after SARSCoV, 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 mink24 and experimentally infected Roborovsky hamsters15 and in some studies with mouseadapted SARS-CoV-2 virus. A limiting factor in documenting the histopathology of human and experimental animal lung disease is the extent of the investigation of the whole lung and its lesions. For experimental animals, few studies use a whole lung section or section of all lobes individually as applied for larger animals to characterize the extent of lesions.23 Some hamster studies have reported the evaluation of the large left lobe15 while others do not report the sampling method. Also, insufflation of lungs with fixative or intravenous perfusion is not often reported. Thus, the actual morphology of the entire infected lung is 1096502 VETXXX10.1177/03009858221096502Veterinary Pathology XX(X)Adissu et al research-article2022