The relationship of headache as a symptom to COVID-19 survival: A systematic review and meta-analysis of survival of 43,169 inpatients with COVID-19

Objective To study the relationship between coronavirus disease 2019 (COVID-19) mortality and headache among patients evaluated for COVID-19 in Emergency Departments and hospitals. Background COVID-19 has disparate impacts on those who contract it. Headache, a COVID-19 symptom, has been associated with positive disease prognosis. We sought to determine whether headache is associated with relative risk of COVID-19 survival. Methods A systematic search in PubMed was performed independently by three reviewers to identify all COVID-19 clinical inpatient series in accordance with the PRISMA guideline. Studies were included if the study design, COVID-19 confirmation method, disease survival ratio, and presence of headache symptom were accessible. We included 48 cohort studies with a total of 43,169 inpatients with COVID-19: 81.4% survived (35,132/43,169) versus 18.6% non-survived (8037/43,169). A meta-analysis of the included studies was then performed. The study was registered on PROSPERO (ID: CRD42021260151). Results When considering headache as a symptom of COVID-19, we observed a significantly higher survival rate (risk ratio: 1.90 [1.46, 2.47], p < 0.0001) among COVID-19 inpatients with headache compared to those without headache. Conclusion Headache among patients with COVID-19 presenting to hospitals may be a marker of host processes which enhance COVID-19 survival. Future studies should further confirm these findings, in order to better understand this relation and to try to address possible limitations related to the inclusion of more severe patients who would be unable to report symptoms (e.g., patients who were intubated).