Supplementary Material for: Gender Disparities in Neurological Symptoms of Long-COVID: A systematic review and meta-analysis

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.

背景：女性性别是已知的长新冠（long-COVID）危险因素。随着新冠病毒感染病例数不断增加，相应的新冠幸存者规模也预计将持续扩大。据我们所知，目前尚无系统综述专门针对长新冠神经系统症状的性别差异展开研究。
方法：本研究从PubMed、Cochrane中心资料库（Central）、Scopus及Web of Science数据库中，检索了确诊新冠病毒感染后至少12周出现特定神经系统症状的女性个体相关研究。检索时限设置为2020年1月1日至2024年6月15日。本研究排除了未提供性别特异性结局数据、非英文文献、病例报告、病例系列及综述类文章。
结果：最终共检索到5632篇符合纳入标准的文献。本研究纳入12项相关研究，涉及6849名患者，其中女性3414名。纳入研究的样本量范围为70至2856，最长随访时长为18个月。最早的文献发表日期为2021年9月16日，最晚为2024年6月11日。针对女性群体，以下神经系统症状的风险比（Risk Ratio, RR）存在显著差异：疲劳（RR=1.40，95%置信区间（Confidence Interval, CI）：1.22~1.60，p<0.001）、头痛（RR=1.37，95%CI：1.12~1.67，p=0.002）、脑雾（brain-fog，RR=1.38，95%CI：1.08~1.76，p=0.011）、抑郁（RR=1.49，95%CI：1.2~1.86，p<0.001）及嗅觉丧失（anosmia，RR=1.61，95%CI：1.36~1.90，p<0.001）。由于各研究采用的研究方法存在差异，疲劳、脑雾及焦虑症状的研究异质性较高。
结论：本研究结果表明，与男性相比，女性罹患长新冠（long-COVID）相关神经系统症状（包括疲劳、头痛、脑雾、抑郁及嗅觉丧失）的风险更高。基于该时间节点后少量研究的有限数据，上述症状的患病率在1年后有所下降。