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Review
. 2021;84(5):307-324.
doi: 10.1159/000516258. Epub 2021 May 27.

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies

Kimia Vakili  1 , Mobina Fathi  2 , Mohammadreza Hajiesmaeili  3 , Melika Salari  4 , Diksha Saluja  5 , Abbas Tafakhori  6 , Fatemeh Sayehmiri  2 , Mostafa Rezaei-Tavirani  7
Affiliations
Review

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies

Kimia Vakili et al. Eur Neurol. 2021.

Abstract

Background: Recently, it has been shown that coronavirus disease 2019 (COVID-19), which has caused a pandemic since December 2019, can be accompanied by some neurological disorders. This study aimed to assess the prevalence of the most common neurological symptoms and comorbidities and systematically review the literature regarding the most prevalent neurological complications of COVID-19 infection.

Methods: All relevant studies had been collected from PubMed, Scopus, Embase, and Web of Science databases. All extracted data were analyzed using Stata version 11.2. The I2 index was applied, and a random-effects model or a fixed-effects model was used for pooled estimation to assess the heterogeneity of studies. Furthermore, Egger and Beeg's tests were used to evaluate the publication bias.

Results: Fifty-seven studies (26 observational and 31 case reports) were included (including 6,597 COVID-19 patients). The most prevalent general symptoms were fever, cough, and dyspnea with 84.6% (95% CI: 75.3-92.1; I2 = 98.7%), 61.3% (95% CI: 55.3-67.0; I2 = 94.6%), and 34.2% (95% CI: 25.6-43.4; I2 = 97.7%), respectively. Neurological symptoms observed among COVID-19 patients were fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea with 42.9% (95% CI: 36.7-49.3; I2 = 92.8%), 35.4% (95% CI: 11.2-64.4; I2 = 99.2%), 28.9% (95% CI: 19.9-38.8; I2 = 96.3%), 25.3% (95% CI: 1.6-63.4; I2 = 99.6%), 10.1% (95% CI: 2.7-21.0; I2 = 99.1%), 6.7% (95% CI: 3.7-10.5; I2 = 87.5%), and 5.9% (95% CI: 3.1-9.5; I2 = 94.5%). The most prevalent neurological comorbidity in COVID-19 was cerebrovascular disease with 4.3% (95% CI: 2.7-6.3; I2 = 78.7%).

Conclusion: The most prevalent neurological manifestations of COVID-19 include fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea. Cerebrovascular disorders can either act as a risk factor for poorer prognosis in COVID-19 patients or occur as a critical complication in these patients. Guillain-Barre syndrome, encephalitis, and meningitis have also been reported as complications of COVID-19.

Keywords: Cerebrovascular disease; Coronavirus disease 2019; Gustatory dysfunction; Headache; Neurological symptoms; Olfactory dysfunction.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Study flow diagram.
Fig. 2
Fig. 2
Forest plot of the prevalence of headache in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 3
Fig. 3
Forest plot of the prevalence of nausea in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 4
Fig. 4
Forest Plot of the prevalence of dizziness in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 5
Fig. 5
Forest plot of the prevalence of fatigue in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 6
Fig. 6
Forest plot of the prevalence of gustatory dysfunction in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 7
Fig. 7
Forest Plot of the prevalence of anorexia in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 8
Fig. 8
Forest plot of the prevalence of olfactory dysfunction in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 9
Fig. 9
Forest Plot of the prevalence of cerebrovascular disease in COVID-19 patients. Each square shows effect estimate of individual studies with their 95% CI. Size of squares is proportional to the weight of each study in the meta-analysis. In this plot, studies are shown in the order of publication date and first author's names (based on a random-effects model). COVID-19, coronavirus disease 2019.
Fig. 10
Fig. 10
Begg's funnel plot for publication bias.
See this image and copyright information in PMC

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