A systematic review uncovers a wide-gap between COVID-19 in humans and animal models

Abstract

Background: Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of humans COVID-19. Methods: We searched the Medline, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1, to May 20, 2020. We used the search terms COVID-19 OR SARS-CoV-2 AND, animal models, hamsters, nonhuman primates, macaques, rodent, mice, rats, ferrets, rabbits, cats, and dogs. Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. Findings: 13 peer-reviewed studies and 14 preprints met inclusion criteria. The animals used were nonhuman primates (n=13), mice (n=7), ferrets (n =4), hamsters (n= 4), and cats (n =1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in Rhesus macaques, hamsters, and mice. Notably, none of the animals unveiled cytokine storm or coagulopathy. Conclusions: Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.

On the whereabouts of SARS-CoV-2 in the human body: A systematic review

“…These limitations could be addressed with an appropriate animal model, replicating the pathogenesis of human COVID-19 [ 207 ]. However, although the mild COVID-19 phenotype and viral replication in the respiratory tract can be mimicked in non-human primates, hamsters, ferrets and cats, none of these animals features the cytokine storm and coagulopathy that characterizes severe COVID-19 in humans [ 208 ]. Therefore, this review primarily focused on SARS-CoV-2 studies in the context of humans.…”

Adult stem cell-derived complete lung organoid models emulate lung disease in COVID-19

“…Of these readouts, the host response, as assessed by ViP signatures, is a key vantage point because an overzealous host response is what is known to cause fatality. Recently, a systematic review of the existing preclinical animal models revealed that most of the animal models of COVID-19 recapitulated mild patterns of human COVID-19; no severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans ( Spagnolo et al, 2020 ) and animal models ( Ehaideb et al, 2020 ). It is noteworthy that alternative models that effectively support viral replication, such as the proximal airway epithelium or iPSC-derived AT2 cells (analyzed in this work) or a fetal lung bud tip-derived organoid model recently described by others ( Lamers et al, 2021 ), do not recapitulate the host response in COVID-19.…”

Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19

“…Of these readouts, the host response, as assessed by ViP signatures, is a key vantage point because an overzealous host response is what is known to cause fatality. Recently, a systematic review of the existing pre-clinical animal models revealed that most of the animal models of COVID-19 recapitulated mild patterns of human no severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans (Spagnolo et al, 2020) and animal models (Ehaideb et al, 2020). The model revealed here, in conjunction with the ViP signatures described earlier (Sahoo et al, 2020), could serve as a pre-clinical model with companion diagnostics to identify drugs that target both the viral and host response in pandemics.…”