Neurological manifestations in COVID‐19 caused by SARS‐CoV‐2

The recent outbreak of COVID-19 caused by SARS-CoV-2 coronavirus has turned the world into chaos with its ominously high rate of transmissions. As the SARS-CoV-2 infection has become pandemic, the scientific community is in a race against time to beat the COVID19 by unraveling molecular targets and discover epitopes in the protein sequences of SARS-CoV-2 for vaccines/antibodies synthesis. It has been reported that in addition to the conventional respiratory complains of flu, patients are also exhibiting neurological signs and symptoms. Recently, the report of a patient with COVID-19 exhibiting loss of the involuntary process of breathing1 controlled by the inspiratory area in the brainstem, is alarming. Additionally, neurological deficits reported in uncomplicated and complicated patients with COVID-192 from hospitals in Wuhan, China, are convincing enough that the neurological deficits could be ongoing in the recent outbreak without getting noticed. As the recent outbreak has now spread to almost all of the continents and has become pandemic, we are in the early phases of our attempts to understand the syndromic complexity of the COVID-19. The SARS-CoV-2 causing COVID-19 can take two pathways to involve the brain (Figure 1). Early occurrences of loss of smell, ataxia, and convulsions should be further evaluated for CNS involvement by SARS-CoV-2. The clinicians throughout the world in general, and Wuhan, China, in particular, are getting the firsthand to study and report the real-time clinical presentations of the patients affected by COVID19. The prognostic and diagnostic significance of neurological sign and symptoms in COVID-19 patients can be gauged by fact that the protocol designed to investigate the First Few X cases (FFX) and their close contacts by the World Health Organization (WHO), includes a separate section for “other neurological signs” in addition to separate columns for respiratory symptoms.3 Additionally, reports of COVID-19-affected individuals experiencing convulsions in prevalent areas is alarming and need to be distinguished from febrile convolution that is expected to occur with high-grade fever in patients with COVID-19. Our experience with taxonomically related SARS-CoV patients in the past has proven beyond doubt the coronaviruses to affect the brain. Of many examples from the past, was a case where SARS-CoV was isolated from the brain of a patient who had exhibited features of neurological deficits on 28th day of infection.4 In past outbreaks with SARS-CoV, it has been shown that it targets the CNS5 and the reports that the brain also is an additional target of SARS-CoV4 raises the possibility of the presentation of more patients with neurological manifestations in the ongoing outbreak of COIVD-19. Also, SARS-CoV has been isolated from brain tissue with edema and neuronal degeneration as seen at autopsies with immunohistochemistry, in situ hybridization, and electron microscopic confirmation of viral infection of the neurons.6 It would not be surprising to see the COVID-19 virus following the same trend as both viruses are near identical taxonomically. As the pandemic is in effect at present, a detailed timeline of the syndromic neurological manifestation in COVID-19 will emerge as more studies get published on complicated and uncomplicated cases of COVID-19. Though the understanding of the pathogenetic mechanisms underlying the CNS invasion will be revealed in time, there is an urgent need to distinguish between neurologically affected CVOID-19 patients and those who do not exhibit the sign and symptoms of CNS involvement. The hematogenous route appears to be the likely pathway for SARS-CoV-2 to reach the brain, but other routes to the CNS like across the cribriform plate (Figure 1B) of the ethmoid bone in proximity to the olfactory bulb7 should be taken into consideration in cases of early-phase COVID-19-affected patients who exhibit loss of smell and taste accompanied with neurological signs and symptoms. Studies believe that direct SARS-CoV infection of the human CNS does occur in some patients.8 It is also important to mention here that the neurological signs and symptoms observed in the COVID-19 cases could be a manifestation of hypoxia, respiratory, and metabolic acidosis at an advanced stage of the disease, but reasonably, a differential diagnosis of these cases is needed, which could prove lifesaving. The later distinction also appears to be important from the vantage point of selecting a treatment regimen, as management of the COVID-19 cases with neurological involvement would require more specific and aggressive treatments as compared to the patients without it. The significance of a thorough neurological assessment of COVID19 patients cannot be overemphasized which can rule-in or rule out a neurological deficit of a patient admitted after serological tests confirming the diagnosis of COVID-19. Presence of neurological deficits