Neurological complications in patients with SARS-CoV-2 infection: a systematic review

Background: SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings.Methods: We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19.Results: A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5% to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-COV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients. Conclusions: Our evidence synthesis led to a categorical analysis of the central and peripheral involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's CNS and PNS involvement and generate strategies for therapeutic decision-making.Registration: This review is registered in PROSPERO (CRD42020193140), July 24, 2020.

Background: Here we performed a systematic review of literature of CSF findings associated with neurological complications in coronavirus disease-2019 (COVID-19) to establish a pattern and understand the significance of CSF analysis which can possibly be useful in deciding prognosis and exploring therapeutic options in the future. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 in cerebrospinal fluid”, “SARS-CoV-2 and CNS Complication”.Results: We performed CSF analysis results in total of 113 patients from 67 papers. There were 7 patients out of 113 patients (6.2 %) were fatal and 35 patients (31 %) were considered severe and rest non-severe. Elevated cell counts (>5 cells/µL) were found in 43% (3/7) of the fatal cases, 25.7% (9/35) of the severe cases and 29.4% (15/51) of non-severe cases. The average CSF protein of 110.0 mg/dl found in fatal, and in 85.4mg/dl in non-fatal cases. Whereas, average CSF protein levels were 78 mg/dl in severe and 103 mg/dl in non-severe cases. In addition, 76.5% (13/17) of the patients with CNS complications and 74.1% (40/54) of the patients with a PNS manifestation showed elevated protein levels.Conclusion: The most common finding of CSF analysis in the setting of neurological manifestations in Covid-19 is noted to be elevated CSF protein with occasionally elevated, predominantly lymphocytic cell count. Interestingly, CSF protein is noted to be majorly elevated in all spectrums of severity of neurological illness including CNS and PNS complications. This may be indicative of only one common pathophysiological mechanism of neurological illness. In future, A combination of SARS-CoV-2 CSF RT-PCR, CSF IgM testing, and CNS targeting antibodies should be further studied to understand pathophysiology of neurological complications in Covid-19.

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