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Table 1 The characteristics of included systematic reviews regarding the general manifestations of COVID-19 infection

From: Neurological manifestations of COVID-19 infection: an umbrella review

Authors Origin Type Quality Number of included studies Types of included studies Assessing the quality of included studies Searched databases Main results
1. Whittaker et al. 2020 [25] UK Systematic review Critically Low 31 Cohort, case report, cross-sectional, case–control None Pubmed, Embase, Scopus, Google Scholar, Cochrane Library, Ovid Headache and anosmia were the most common neurological manifestations of SARS-CoV-2 in hospitalized patients. Less common symptoms include seizure, stroke and isolated cases of GBS1
2. Wang et al. 2020 [18] China Systematic review + meta-analysis Critically Low 41 Case series, case report, cross-sectional, case–control, letters NIH2 quality assessment tool Pubmed, Embase, Scopus, medRxiv, bioRvix The most common manifestationswere fatigue, anorexia, dyspnea/shortness of breath, and malaise. The common specific neurological symptoms included OGD3, especially in mild cases. GBS and acute inflammation of the brain, spinal cord, and meninges
3. Chen et al. 2020 [20] Germany Systematic review Moderate 92 Cohort, case series, case report, case–control, letters 1. Criteria for diagnosis of Covid-192. Laboratory confirmation method 3. The respiratory specimens used for testing Pubmed, medRxiv, bioRxiv, Three Chinese databases Headache, dizziness, taste and smell dysfunctions, and impaired consciousness were the most frequently described neurological symptoms
4. Neishaboori et al. 2020 [15] Iran Systematic review + meta-analysis Moderate 7 Cohort, case series, case–control NHLBI4 quality assessment tool Pubmed, Embase, Scopus, Web of Science The most common type of CNS5 complications included encephalopathy and acute cerebrovascular disease
5. Di Carlo et al. 2020 [21] Italy Systematic review Moderate 19 Cohort, case series, case report, case–control Modified NOS6 Pubmed, Embase Headache, dizziness, OGD were reported in patients, three studies reported radiological confirmed acute cerebrovascular disease
6. Asadi-Pooya et al. 2020 [26] Iran Systematic review Critically Low 8 Cohort, case series, case report None Pubmed, Scopus Nonspecific neurological symptoms, such as confusion and headache were reported in COVID-19 patients. A few patients also showed more specific manifestations, such as seizure or cerebrovascular problems
7. Nepal et al. 2020 [28] Nepal Systematic review Critically Low 37 Cohort, case series, case report, case–control None Pubmed, Google Scholar, Chinese National Knowledge Infrastructure, Research square, medRxiv, Social Science Research Network, and ChinaXiv The most commonly reported neurological manifestations of COVID-19 weremyalgia, headache, altered sensorium and OGD. Uncommonly, COVID-19 can also present with CNS manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, PNS7 manifestations such as GBS and Bell’s palsy, and skeletal muscle manifestations such as rhabdomyolysis are also reported
8. Taherifard et al. 2020 [27] Iran Systematic review Critically Low 22 Case series, case report None Pubmed, Scopus, Web of Science The virus seemed to affect both PNS and CNS. The most frequently reported neurological complication was acute ischemic cerebrovascular accident, followed by GBS syndrome
9. Ghannam et al. 2020 [31] USA Systematic review Moderate 42 Case series, case report JBI8 Critical Appraisal Tool Pubmed, Ovid Medline COVID-19 patients demonstrated cerebrovascular insults, neuromuscular disorders, and encephalitis or encephalopathy
10. Abdullahi et al. 2020 [11] Nigeria Systematic review + meta-analysis Moderate 60 Cohort, case series, case report, cross-sectional, case–control Modified McMaster critical review form Pubmed, Embase, Google Scholar, Web of Science The most common type of neurological and musculoskeletal manifestations were as followed: OGD, myalgia, headache, back pain, dizziness, acute cerebrovascular disease and impaired consciousness
11. Cagnazzo et al. 2020 [19] France Systematic review Moderate 39 Case series, case–control Modified NOS Pubmed, Embase, Scopus Headache, muscle injury, psychiatric involvement, impaired consciousness, OGD, acute cerebrovascular events and dizziness were the most frequently reported neurological manifestations. Less common ones were ischemic stroke, cranial nerve impairment, nerve root and plexus disorders, epilepsy, and hemorrhagic stroke
12. Collantes et al. 2020 [13] Philippines Systematic review + meta-analysis High 35 Cohort, case series, case report, case–control Murad tool Pubmed, Embase, Scopus, WHO database The most common type of neurological involvements were headache, dizziness, headache and dizziness, nausea, vomiting, nausea and vomiting, confusion and myalgia. The most common neurological complication associated with COVID-19 was vascular disorders; others included encephalopathy, encephalitis, oculomotor nerve palsy, isolated sudden-onset anosmia, GBS, and Miller–Fisher syndrome
13. Orrù et al. 2020 [22] Italy Systematic review Critically Low 87 Cohort, case report, case–control, in-press articles None Pubmed, Scopus OGD, ischemic/hemorrhagic stroke, meningoencephalitis and encephalopathy, including acute necrotizing encephalopathy were commonly associated with COVID-19; PNS involvements included, GBS and Miller Fisher syndromes
14. Favas et al. 2020 [14] India Systematic review + meta-analysis High 212 Cohort, experimental, case report, cross-sectional, case–control, letters NOS, CONSORT9 Pubmed, Embase, Scopus, Google Scholar, Cochrane Library, Web of Science, WHO database, EBSCO, Clinicaltrial.gov OGD, myalgia, headache, dizziness, and syncope are reported in COVID-19. Ischemic stroke, followed by hemorrhagic stroke, and cerebral venous thrombosis were also reported
15. Munhoz et al. 2020 [29] Brazil Systematic review Critically Low 43 Cohort, experimental, case series, case report, case–control None Pubmed, LILACS Non-specific symptoms, such as hyposmia and myalgia, to more complex and life-threatening conditions, such as cerebrovascular diseases, encephalopathies, and GBS are associated with COVID-19 infection
16. Romoli et al. 2020 [23] Italy, Austria, Zurich, Switzerland Systematic review Moderate 27 Cohort, case series, case report, cross-sectional, case–control NOS Pubmed, Embase, Google Scholar, medRxiv, ChinaXiv Cases of OGD, GBS, Miller-Fisher syndrome, cranial neuropathy, meningitis, encephalitis, and various other conditions were linked to COVID-19
17. Pinzon et al. 2020 [16] Indonesia Systematic review + meta-analysis Moderate 33 Cohort, experimental, case report, ross-sectional, case–control The Oxford CEBM12 Pubmed Myalgia was the most common, neurologic symptom of COVID-19, followed by headache, dizziness; nausea with or without vomiting; concurrent cerebrovascular disease; and impaired consciousness
18. Chua et al. 2020 [12] Singapore Systematic review + meta-analysis Critically Low 48 Cohort, case series, case report, cross-sectional, case–control, letters, rapid comments None Pubmed, Google Scholar Stroke is the most frequently reported neurological manifestation in COVID-19 and has the highest mortality rate. Other manifestations included GBS and variants, meningitis, encephalitis, encephalopathy, myelitis and seizures
19. Scoppettuolo et al. 2020 [24] Switzerland, Belgium Systematic review Critically Low 42 Case series, case report None Pubmed, Scopus, Cochrane Library Neurological complications of SARS-CoV-2 are mainly related to OGD, cerebrovascular disease and PINS10 are rare
20. Tsai et al. 2020 [17] Taiwan Systematic review + meta-analysis Critically Low 79 Case series, case report None Pubmed, Embase, Cochrane Library OGD, myalgia, headache, acute cerebral vascular disease, dizziness, altered mental status, seizure, encephalitis, neuralgia, ataxia, GBS, Miller Fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture were demonstrated in COVID-19 patients
21. Ibrahim 2020 [30] Egypt Systematic review Critically Low 20 Cohort, experimental, case series, case report, cross-sectional None Pubmed, Scopus, Cochrane Library, clinicaltrials.gov CNS symptoms was more common compared to the PNS. Headache was the most common neurological symptoms in regard to number of patients, meanwhile dizziness had the highest incidence
  1. 1. GBS: Guillain–Barré syndrome, 2. NIH: National Institutes of Health, 3. OGD: Olfactory and Gustatory Disorder, 4. NHLBI: National Heart, Lung, and Blood Institute, 5. CNS: central nervous system, 6. NOS: Newcastle–Ottawa Scale, 7. PNS: Peripheral Nervous System, 8. JBI: Joanna Briggs Institute, 9. CONSORT: Consolidated Standards of Reporting Trials, 10. PINS: Post-infection Neurological Syndrome. P value < 0.05 was considered to be statistically significant