Gender Disparities in Neurological Symptoms of Long COVID: A Systematic Review and Meta-Analysis

Abstract

Background- Female sex is a known risk factor for long-COVID. With the increasing number of COVID-19 cases, the corresponding number of survivors is also expected to rise. To the best of our knowledge, no systematic review has specifically addressed the gender differences in neurological symptoms of long-COVID. Methods: We included studies on female individuals who presented with specific neurological symptoms at least 12 weeks after confirmed COVID-19 diagnosis from PubMed, Central, Scopus, and Web of Science. The search limit was put for after 01/2020 until 15/06/2024. We excluded studies that did not provide sex-specific outcome data, those not in English, case reports, case series, and review articles. Results: A total of 5632 eligible articles were identified. This article provides relevant information from 12 studies involving 6849 patients, of which 3414 were female. The sample size ranged from 70 to 2856, with a maximum follow-up period of 18 months. The earliest publication date was 16/09/2021 while the latest was 11/06/2024. The following neurological symptoms had significant difference in risk ratio (RR) for female gender: fatigue RR 1.40 (95% confidence interval (CI): 1.22 – 1.60, p<0.001), headache RR 1.37 (95% CI: 1.12 – 1.67, p=0.002), brain-fog RR 1.38 (95% CI 1.08-1.76, p=0.011) depression RR 1.49 (95% CI: 1.2 – 1.86, p<0.001), and anosmia RR 1.61 (95% CI: 1.36 – 1.90, p<0.001). high heterogenicity was found for fatigue, brain fog, and anxiety due to the diverse methodologies employed in the studies. Conclusion- Our findings suggest that women are at a higher risk for long-COVID neurological symptoms, including fatigue, headaches, brain fog, depression, and anosmia, compared to men. The prevalence of these symptoms decreases after one year, based on limited data from the small number of studies available beyond this period.