Supplementary Material for: Intestinal inflammation and permeability in patients recovered from SARS-CoV-2 infection.

Introduction: Different works suggest a close link between Long COVID Gastrointestinal (GI) manifestations
and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae.

Methods: Eighty-six subjects attending the Post-COVID Service and recovered from SARS-CoV-2 infection for six months, were investigated for Long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC), and
permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and The Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants.

Results: Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p=0.03), although remaining quite close to the normal range. No significant differences were shown
regarding the assessment of intestinal permeability. By GIQLI, long-term gastrointestinal sequelae were inversely correlated with quality of life (p=0.009).

Conclusion: Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post‐COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.

引言：多项研究表明，长新冠胃肠道（GI）表现与感染后肠-脑互动障碍（PI-DGBIs，全称post-infection disorders of gut-brain interaction）存在密切关联。然而，长期胃肠道后遗症的潜在发病机制仍未明确。本研究旨在评估新型冠状病毒（SARS-CoV-2）感染康复者的肠道炎症与肠道通透性情况，并分析其与长期胃肠道后遗症的潜在相关性。

方法：本研究纳入86名于新冠后遗症门诊就诊、且感染SARS-CoV-2已满6个月的康复受试者，对其长新冠表现进行评估。对于存在长期胃肠道症状的受试者，采用罗马IV问卷（Rome IV questionnaire）进一步评估其PI-DGBIs情况。所有受试者均接受肠道炎症指标（粪便钙卫蛋白，fecal calprotectin, FC）与肠道通透性指标（血清及粪便连蛋白（zonulin）水平）检测。此外，所有受试者均完成医院焦虑抑郁量表（Hospital Anxiety and Depression Scale, HADS）与胃肠道生活质量指数（Gastrointestinal Quality of Life Index, GIQLI）问卷调研。

结果：37名受试者（占比43%）存在长期胃肠道症状，其余49名受试者（占比57%）无相关症状。其中33名受试者符合PI-DGBIs的罗马IV诊断标准。无胃肠道症状的受试者粪便钙卫蛋白（FC）水平更高（p=0.03），但仍处于正常参考范围内。肠道通透性相关指标未观察到显著组间差异。通过胃肠道生活质量指数（GIQLI）评估发现，长期胃肠道后遗症与生活质量呈负相关（p=0.009）。

结论：长新冠胃肠道症状的潜在发病机制似乎并非局部炎症反应所致。鉴于新冠后DGBIs会带来医疗、经济及社会负担，应加强对这一新兴病症的研究，以优化受累受试者的管理方案。