Data_Sheet_1_The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study.pdf

BackgroundLong COVID is a clinical entity characterized by persistent health problems or development of new diseases, without an alternative diagnosis, following SARS-CoV-2 infection that affects a significant proportion of individuals globally. It can manifest with a wide range of symptoms due to dysfunction of multiple organ systems including but not limited to cardiovascular, hematologic, neurological, gastrointestinal, and renal organs, revealed by observational studies. However, a causal association between the genetic predisposition to COVID-19 and many post-infective abnormalities in long COVID remain unclear.
MethodsHere we employed Mendelian randomization (MR), a robust genetic epidemiological approach, to investigate the potential causal associations between genetic predisposition to COVID-19 and long COVID symptoms, namely pulmonary (pneumonia and airway infections including bronchitis, emphysema, asthma, and rhinitis), neurological (headache, depression, and Parkinson’s disease), cardiac (heart failure and chest pain) diseases, and chronic fatigue. Using two-sample MR, we leveraged genetic data from a large COVID-19 genome-wide association study and various disorder-specific datasets.
ResultsThis analysis revealed that a genetic predisposition to COVID-19 was significantly causally linked to an increased risk of developing pneumonia, airway infections, headache, and heart failure. It also showed a strong positive correlation with chronic fatigue, a frequently observed symptom in long COVID patients. However, our findings on Parkinson’s disease, depression, and chest pain were inconclusive.
ConclusionOverall, these findings provide valuable insights into the genetic underpinnings of long COVID and its diverse range of symptoms. Understanding these causal associations may aid in better management and treatment of long COVID patients, thereby alleviating the substantial burden it poses on global health and socioeconomic systems.

背景
长期新冠（Long COVID）是一种临床病症，指在感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）后出现持续健康问题或新发疾病，且无其他替代诊断依据，在全球范围内影响了相当比例的人群。观察性研究显示，该病症可因多器官系统功能障碍出现广泛症状，涉及心血管、血液、神经、胃肠及肾脏等多个系统（但不限于上述范围）。不过，新冠感染的遗传易感性与长期新冠诸多感染后异常之间的因果关联仍不明确。
方法
本研究采用孟德尔随机化（Mendelian randomization, MR）这一稳健的遗传流行病学方法，探究新冠遗传易感性与长期新冠症状之间的潜在因果关联，所关注的症状包括肺部疾病（肺炎及气道感染，涵盖支气管炎、肺气肿、哮喘与鼻炎）、神经系统疾病（头痛、抑郁症及帕金森病）、心脏疾病（心力衰竭与胸痛）以及慢性疲劳。本研究采用双样本孟德尔随机化方法，利用大型新冠全基因组关联研究（genome-wide association study）及多种疾病特异性数据集的遗传数据开展分析。
结果
本分析显示，新冠遗传易感性与肺炎、气道感染、头痛及心力衰竭的发病风险升高存在显著因果关联。同时，其与长期新冠患者中常见的慢性疲劳也存在较强的正相关关系。不过，针对帕金森病、抑郁症及胸痛的分析结果尚未明确。
结论
综上，本研究结果为长期新冠的遗传基础及其多样症状提供了有价值的见解。阐明此类因果关联或有助于优化长期新冠患者的管理与治疗方案，进而减轻该疾病对全球卫生及社会经济系统造成的沉重负担。