Comba Isin Y, Mars Ruben A T, Yang Lu, Dumais Mitchell, Chen Jun, Van Gorp Trena M, Harrington Jonathan J, Sinnwell Jason P, Johnson Stephen, Holland LaRinda A, Khan Adam K, Lim Efrem S, Aakre Christopher, Athreya Arjun P, Gerber Georg K, O'Horo Jack C, Lazaridis Konstantinos N, Kashyap Purna C
bioRxiv. 2024 Dec 11:2024.12.10.626852. doi: 10.1101/2024.12.10.626852.
Long COVID (LC), manifests in 10-30% of non-hospitalized individuals post-SARS-CoV-2 infection leading to significant morbidity. The predictive role of gut microbiome composition during acute infection in the development of LC is not well understood, partly due to the heterogeneous nature of disease. We conducted a longitudinal study of 799 outpatients tested for SARS-CoV-2 (380 positive, 419 negative) and found that individuals who later developed LC harbored distinct gut microbiome compositions during acute infection, compared with both SARS-CoV-2-positive individuals who did not develop LC and negative controls with similar symptomatology. However, the temporal changes in gut microbiome composition between the infectious (0-1 month) and post-infectious (1-2 months) phases was not different between study groups. Using machine learning, we showed that microbiome composition alone more accurately predicted LC than clinical variables. Including clinical data only marginally enhanced this prediction, suggesting that microbiome profiles during acute infection may reflect underlying health status and immune responses thus, help predicting individuals at risk for LC. Finally, we identified four LC symptom clusters, with gastrointestinal and fatigue-only groups most strongly linked to gut microbiome alterations.
长期新冠(LC)在10%-30%的非住院新冠病毒感染个体中出现,导致显著的发病率。肠道微生物群组成在急性感染期间对LC发生发展的预测作用尚未完全明确,部分原因是该疾病的异质性。我们对799名接受新冠病毒检测的门诊患者进行了一项纵向研究(380例阳性,419例阴性),发现与未发生LC的新冠病毒阳性个体以及有相似症状的阴性对照相比,后来发生LC的个体在急性感染期间肠道微生物群组成不同。然而,研究组之间在感染期(0-1个月)和感染后期(1-2个月)肠道微生物群组成的时间变化并无差异。使用机器学习,我们发现仅微生物群组成比临床变量更准确地预测了LC。仅纳入临床数据仅略微增强了这一预测,表明急性感染期间的微生物群特征可能反映了潜在的健康状况和免疫反应,从而有助于预测有LC风险的个体。最后,我们确定了四个LC症状群,其中胃肠道症状群和仅疲劳症状群与肠道微生物群改变的关联最为密切。