The world-wide pandemic involving SARS-CoV2 in which high infectivity and pathogenesis necessitated the critical need for rapid and accurate preclinical modeling of this new virus. Unfortunately, the species-restricted tropism of the CoV2 spike protein towards human and not mouse ACE2, seriously hampered the ability to understand pathogenesis and potential efficacy of potential therapeutics and vaccines. Vaccine responses are particularly imperative given the likely need for continuous vaccine administration and viral evasion processes. This barrier necessitated the development of genetically altered mouse models or adapting the virus to infect murine cells.

The immune responses underlying SARS-CoV2 infection are complex as are the immunopathology associated with infection and resolution in which multiple organs and tissues are affected. This is highlighted by the occurrence of prolonged pathology and symptoms termed “Long Covid” well after resolution of infection and also coupled with the high mutation rate of the virus. Preclinical models allow for mechanistic dissection of the pleiotropic effects of the virus as well as vaccine responses. These can include mouse models but also involve non-human primate models, all of which have advantages but limitations that must be considered when extrapolating to humans. Preclinical models may also include in vitro modeling components.

This collection seeks manuscripts consisting of reviews or primary data that may include, but are not limited to:

• Different aspects of preclinical CoV2 modeling in which the pathogenesis of the virus and the role the immune system plays in various affected tissues (pulmonary, hematopoietic, neurological) and readouts used.
• Factors that affect immune responses (age, sex, body fat, species, genetic alteration allowing for CoV2 infection, strain of mouse, time after challenge, etc)
• Similarities and differences with original SARS-CoV models
• Components of the virus or vaccine (formulation, adjuvants, target antigen) itself which can affect immune responses and the different components of the immune responses (innate, adaptive, cytokines) will all be covered.

Attempts to link to clinical data or other species also are encouraged. Particular attention will be given for acknowledging the caveats or limitations of the preclinical models used and issues still needing to be addressed.

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Frontiers in Immunology

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