Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis [version 2; peer review: 2 approved]

Abstract

<ns3:p> <ns3:bold>Background</ns3:bold> : This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. </ns3:p> <ns3:p> <ns3:bold>Methods</ns3:bold> : Available articles from PubMed, Scopus, and Web of Science were searched as of September 2 <ns3:sup>nd</ns3:sup> , 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. </ns3:p> <ns3:p> <ns3:bold>Results</ns3:bold> : We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. </ns3:p> <ns3:p> <ns3:bold>Conclusion</ns3:bold> : Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. </ns3:p> <ns3:p> <ns3:bold>PROSPERO registration</ns3:bold> : <ns3:ext-link xmlns:ns4="http://www.w3.org/1999/xlink" ext-link-type="uri" ns4:href="https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=210332">CRD42020210332</ns3:ext-link> (28/09/2020) </ns3:p>

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