Introduction
The neuroinvasive potential of the Severe Acute Respiratory Syndrome novel coronavirus, SARS-CoV-2, is being recognized, with enhanced awareness that the associated infection, Coronavirus Diseases 2019 (COVID-19), might result in neurological injury. Indeed, there is a growing body of evidence to suggest that a subset of COVID-19 patients will experience neurological manifestations of the infection [1]. Since genomic studies show that the SARS-CoV-2 virus has similar homological sequences with two of its beta-coronavirus predecessors, the SARS-CoV associated with Severe Acute Respiratory Syndrome (SARS) [2] and the virus associated with Middle Eastern Respiratory Syndrome (MERS) [3], it is helpful to review the neurological symptoms of these two earlier diseases as the plausible link between COVID-19 and neurological symptoms are explored. Furthermore, the pathophysiological pathways of these three conditions (COVID-19, SARS, and MERS) might be expected to be similar [4–6]. Neurotropism has been observed in both MERS and SARS [7–9], and there are early findings of certain neurological manifestations in COVID-19 patients [4,10]. The RNA of the SARS-CoV-2 virus has been identified in the cerebrospinal fluid of a COVID-19 patient, demonstrating its neurotropic potential. It is clinically relevant to determine how the SARS-CoV-2 virus can access the central nervous system (CNS) and whether the neuronal injury caused by the virus might be connected to the injury of the autonomic nervous system.
The transmission of a novel infectious pathogen among humans such as the SARS-CoV-2 may be complicated, but it is far from rare. As many as 75% of emerging human infections have some connection to a zoonotic disease [11]. Typically, viral, bacterial, fungal, or parasitical pathogens may emerge due to one or a combination of factors: human and animal interaction, changes in human or animal behavior, consumption of exotic animal foods, globalization, world travel, or things that disrupt human and animal interactions, such as wars, natural disasters, and environmental changes. The pathogen itself may play a role in its pattern of emergence by mutation; in some instances, humans may facilitate the rapid progress of these mutations by the use of antimicrobials. Thus, while often multifactorial and complex, the sudden emergence of a novel infectious agent is not a novelty [12]. The novel SARS-CoV-2 virus, which first appeared in 2019, is just one of several coronaviruses that have caused epidemics in the past two decades. These pathogens are sometimes able to adapt to new hosts, as occurred with the zoonotic SARS-CoV-2 virus, which appears to have originated in bats, then rapidly accommodated to human hosts [13].
Coronaviruses are single-stranded, positive-sense, enveloped RNA viruses in the nidovirales order that are categorized into four genera: alpha, beta, gamma, and delta. The SARS-CoV-2 virus associated with the COVID-19 epidemic is a beta-coronavirus. Seven known coronaviruses affect humans: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2. Many coronavirus-related illnesses are mild. In fact, coronaviruses were first studied in the 1960s as being agents of the common cold [14]. Nevertheless, of these viruses, only MERS-CoV, SARS-CoV, and SARS-CoV-2 are associated with potentially severe symptoms and fatal outcomes [15].
Once in the body, viruses may invade the CNS through hematogenous spread defined by viremia. Viruses may also enter the CNS through retrograde neuronal dissemination, which occurs when the virus infects peripheral neurons, subsequently spreading to the spine and brain by way of the existing neuronal transport mechanisms.
It is the aim of this narrative review to describe what is known about neurological manifestations of SARS, MERS, and COVID-19, with special emphasis on reports about neurological symptoms in COVID-19.