Comparison of model‐specific histopathology in mouse models of COVID‐19

Abstract

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS‐CoV‐2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock‐in strains, and viral vector‐mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS‐CoV‐2 are unknown. Here, we perform systematic comparisons of the mouse models including K18‐hACE2 mice, KI‐hACE2 mice, Ad5‐hACE2 mice and CAG‐hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS‐CoV‐2 researches. The similarities or differences among the model‐specific pathologies may help in better understanding the pathogenic process of SARS‐CoV‐2 infection and aiding in the development of effective medications and prophylactic treatments for SARS‐CoV‐2.

Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

“…The paraffin-embedded tissue sections were stained with H&E for evaluation of the histopathological score by a pathologist. The semiquantitative scoring system (0 - normal, 1 - mild, 2 - moderate, and 3 - severe) was applied by examining the tissues under digital microscopy as described previously ( Winkler et al, 2020 ; Yang et al, 2022 ; Zheng et al, 2021 ). Immunoreactivity in the lung tissues was assessed using a rabbit anti-SARS-CoV-2 Nucleocapsid pAb as the primary antibody (Sinobiological, China) and further processed using a Ventana Discovery Ultra (Roche, USA) system.…”

Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

“…The paraffin-embedded tissue sections were stained with H&E for evaluation of the histopathological score by a pathologist. The semiquantitative scoring system (0 - normal, 1 - mild, 2 - moderate, and 3 - severe) was applied by examining the tissues under digital microscopy as described previously (18, 45, 46). The cumulative scoring system was applied by considering perivascular inflammation, bronchiolar epithelial necrosis, bronchiolar epithelial necrosis regeneration, bronchiolar inflammation, alveolar inflammation, and perivascular edema.…”

Early pathogenesis profiles across SARS-CoV-2 variants in K18-hACE2 mice revealed differential triggers of lung damages

“…The use of K18-hACE2 murine model to understand SARS-CoV-2 infection has been instrumental to the understanding of SARS-CoV-2 pathogenesis mechanisms since the start of the pandemic, including comparisons of early clades’ differential severity ( 13 , 30 – 34 ). Moreover, the K18-hACE2 mice were shown to be simulating severe SARS-CoV-2 infection useful in the identification of immune responses leading to severe outcome ( 35 ). Hence, here we reported results using the model to correlate early cytokine profiles (4 dpi) of early SARS-CoV-2 evolutionary iterations (L, V, G, GR), and the VOCs Alpha (GRY-α), Beta (GH-β), Delta (GK-δ) and Omicron (GRA-o), with their infection outcome.…”