Advances and gaps in SARS-CoV-2 infection models

Abstract

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.

Fig 1. SARS-CoV-2 VOC in animal models.

The schematic summarizes findings related with virulence, transmission, and cross-protection gathered in the indicated animal models so far. Figure created with Biorender (Biorender.com). huACE2, human angiotensin I-converting enzyme 2; K18, cytokeratin-18; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; VOC, variant of concern.

Fig 2. Animal models and immunobridging.

Comparative and standardized studies in animal models such as those performed by WHO-COM scientists can help to extrapolate vaccine immunogenicity data across preclinical and clinical studies. Figure created with Biorender (Biorender.com). VAERD, vaccine-associated enhanced respiratory disease; VOC, variant of concern; WHO-COM, WHO COVID-19 Modeling group.