Preclinical coronavirus studies and pathology: Challenges of the high-containment laboratory

Abstract

The COVID-19 pandemic has highlighted the critical role that animal models play in elucidating the pathogenesis of emerging diseases and rapidly analyzing potential medical countermeasures. Relevant pathologic outcomes are paramount in evaluating preclinical models and therapeutic outcomes and require careful advance planning. While there are numerous guidelines for attaining high-quality pathology specimens in routine animal studies, preclinical studies using coronaviruses are often conducted under biosafety level-3 (BSL3) conditions, which pose unique challenges and technical limitations. In such settings, rather than foregoing pathologic outcomes because of the inherent constraints of high-containment laboratory protocols, modifications can be made to conventional best practices of specimen collection. Particularly for those unfamiliar with working in a high-containment laboratory, the authors describe the logistics of conducting such work, focusing on animal experiments in BSL3 conditions. To promote scientific rigor and reproducibility and maximize the value of animal use, the authors provide specific points to be considered before, during, and following a high-containment animal study. The authors provide procedural modifications for attaining good quality pathologic assessment of the mouse lung, central nervous system, and blood specimens under high-containment conditions while being conscientious to maximize animal use for other concurrent assays.

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

“…Hibret A. Adissu 1 , David K. Meyerholz 2 , Amanda J. Martinot 3 , and Jerrold M. Ward 4 Veterinary Pathology 59 (4) frequently not well visualized, standardized, or described. This situation is especially true for NHPs and humans.…”

“…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.…”

“…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.…”

“…Also, insufflation of lungs with fixative or intravenous perfusion is not often reported. Thus, the actual morphology of the entire infected lung is 1096502V ETXXX10.1177/03009858221096502Veterinary Pathology XX(X)Adissu et al research-article2022 1 Independent Researcher, Gaithersburg, MD 2 The University of Iowa, Iowa City, IA 3 Tufts University, North Grafton, MA 4 Global VetPathology, Montgomery Village, MD Corresponding Author: Hibret A. Adissu, Independent Researcher, Gaithersburg, MD 20878, USA. Email: hibretadissu@gmail.com…”

“…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…”