nCoV-2019 infection induced neurological outcome and manifestation, linking its historical ancestor SARS-CoV and MERS-CoV: a systematic review and meta-analysis

Abstract

The first systematic review and meta-analysis to help clinician to identify early signs and symptoms of neurological manifestation in COVID-19 positive patients which will further help in early management of patients. Present systematic review and meta-analysis aimed to discuss the prevalence of neurological involvement of the 2019-nCoV patients and assess the symptomatic trend of events as compared to the 2002 “SARS” and 2012 “MERS” pandemics. The articles were systematically screened through several search engine and databases. The articles published or in preprint were included in the study till 15th May 2020. The systematic review done as per the published literatures which included 31 cross sectional, observational studies and case reports which revealed neurological signs and symptoms in SARS-COV-2 disease. For meta-analysis, we included 09 observational and cross-sectional studies which included COVID-19 positive patients and assessed the predominance of various neurological signs and symptoms in COVID-19 patients with relation to SARS-2002 and MERS-2012. Data was analyzed by using the “MedCalc” Statistical Software version 19.2.6 and reported as pooled prevalence. Standard I2 test was used to analyze the heterogeneity. We have collected and screened about a total 2615articles, finally we have included 31articles for the systematic review and 09 for meta-analysis as per the inclusion/exclusion criteria. The analysis was made as per the prevalence rate of neurological symptoms in COVID-19 positive patients. The cumulative neurological outcome of SARS-2002 and MERS-2012 was assessed to get the trends which was further tried to correlate the events with the current pandemic. During the analysis severity and outcome of neurological manifestations range from simple headache to vague non-focal complaints to severe neurologic impairment associated with seizure or meningitis. Central and peripheral nervous system (CNS/PNS) manifestations were seen during the SARS-2002, MERS-2012 and COVID-19. However, none of the publication had primary or secondary objectives of searching neurological manifestations in the COVID-19 patients and the pathogenic mechanism which will subsequently strengthen the importance to start more prospective clinical trials. The prevalence of neurological signs and symptoms were taken as primary objective. Thereafter, the prevalence of each CNS/PNS symptoms was categorized and their prevalence studied. The selection of Bagheri et al., 2020 may be discussed because they have done the cross-sectional study with the neurological finding and correlated the data with prevalence of the COVID-19 positive patients. The proportion of patients presenting with neurological outcome and clinical/PCR positivity were done. We had searched and followed all the possible online/web source, still the data collection process may remain a limitation of work due to addition of several publications on COVID-19 every day. Due to lack of data of SARS-CoV and MERS-CoV, we have included the case reports, MERS and COVID-19 in CNS/PNS manifestations.

COVID-19-Associated Encephalopathy (COVEP): Basic Aspects of Neuropathology

“…As a multisystem infection, it is essential not to underestimate or focus the chronic or acute sequelae of COVID-19 purely to the respiratory system [21,[23][24][25]. A myriad of symptoms in the acute and chronic phases of the disease show signs of its effect on the central nervous system-anosmia, ageusia, migraine headaches, confusion, clouding of consciousness, memory problems, etc., [8,22,[26][27][28].…”

“…Coronaviruses, as a diffuse group of viruses, have shown many properties and organ targets in their biology [3,6,[29][30][31]. The previous two coronaviruses of concern-severe acute respiratory syndrome coronavirus (SARS) and middle eastern respiratory syndrome coronavirus (MERS)-also had signs pointing toward central nervous system involvement, including morphological ones [26,29,[32][33][34]. Furthermore, close relatives to SARS-CoV-2 have been known to cause encephalitis in other animals, such as the mouse hepatitis virus, which is known to have significant neurotropic properties [35][36][37].…”

“…Reports on meningitis and meningeal involvement in COVID-19 are relatively scarce. Most scientific literature reports signs of meningism-severe headaches, disorientation, and neck stiffness, with some also noting seizures [26,38,63]. In most of these cases, aseptic meningitis is diagnosed in a predominantly severe clinical course setting, although in some patients, meningism may be the initial presentation of the disease [26,63].…”

“…Most scientific literature reports signs of meningism-severe headaches, disorientation, and neck stiffness, with some also noting seizures [26,38,63]. In most of these cases, aseptic meningitis is diagnosed in a predominantly severe clinical course setting, although in some patients, meningism may be the initial presentation of the disease [26,63]. Only a handful of reports were able to isolate SARS-CoV-2 from the cerebrospinal fluid of such patients [64,65].…”

“…Given the mechanisms described so far and their inevitable neuronal degeneration and necrosis spectrum of sequelae, they are predominantly the ones occurring in severe and fatal cases [26,68,89]. Accumulating evidence suggests additional mechanisms associated with SARS-CoV-2 infection that could trigger or accelerate already-developed neurodegenerative disorders [117,118].…”