Animal Models for the Study of Neurologic Manifestations Of COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the worldwide coronavirus (COVID-19) pandemic, has infected an estimated 525 million people with over 6 million deaths. Although COVID-19 is primarily a respiratory disease, an escalating number of neurologic symptoms have been reported in humans. Some neurologic symptoms, such as loss of smell or taste, are mild. However, other symptoms, such as meningoencephalitis or stroke, are potentially fatal. Along with surveys and postmortem evaluations on humans, scientists worked with several animal species to try to elucidate the causes of neurologic symptoms. Neurologic sequelae remain challenging to study due to the complexity of the nervous system and difficulties in identification and quantification of neurologic signs. We reviewed animal models used in the study of neurologic COVID-19, specifically research in mice, hamsters, ferrets, and nonhuman primates. We summarized findings on the presence and pathologic effects of SARS-CoV-2 on the nervous system. Given the need to increase understanding of COVID-19 and its effects on the nervous system, scientists must strive to obtain new information from animals to reduce mortality and morbidity with neurologic complications in humans.

Figure 1.

Overview of hypothesized COVID-19 mechanisms of neuropathogenesis and symptoms observed in humans. Abbreviations, ACE2: angiotensin-converting enzyme 2, NRP1: neuropilin 1, TLR2: toll-like receptor 2, OE: olfactory epithelium.

Figure 2.

Chart comparing animal models of COVID to the human condition, and relevant neurologic findings. Abbreviations: NR, none reported.