Clearance of gut mucosal SARS-CoV-2 antigens and post-acute COVID-19 after two years in patients with inflammatory bowel disease, 2024, Zollner et al.

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Clearance of gut mucosal SARS-CoV-2 antigens and post-acute COVID-19 after two years in patients with inflammatory bowel disease
Andreas Zollner; Robert Koch; Almina Jukic; Alexandra Pfister; Moritz Meyer; Nikolaus Wick; Georg Wick; Annika Rössler; Janine Kimpel; Timon E. Adolph; Herbert Tilg

Persistent SARS-CoV-2 antigens in human tissue long beyond acute SARS-CoV-2 infection could be a cause of post-acute COVID-19, also termed long-COVID. In our previous endoscopy study in patients with inflammatory bowel diseases (IBD), we linked viral antigen persistence in the gut mucosa ~7 months after acute infection with symptoms compatible with post-acute COVID-19. Whether patients are able to clear SARS-CoV-2 antigens and related symptoms is unknown.

Here, we report clearance of gut mucosal antigen persistence and restoration of serotonin concentration along with resolution of post-acute COVID-19 symptoms in IBD patients after 2 years, corroborating the link between viral antigen persistence and post-acute COVID-19.

Link | PDF (Gastroenterology)

 

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Follows on from Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases (2022, Gastroenterology)

 

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In the patients who received endoscopic examination, biopsy specimens from the duodenum, ileum and colon were obtained for comprehensive SARS-CoV-2 antigen assessment by qPCR and confocal immunofluorescence, as previously described, and patient characteristics are detailed in Supplementary Table 2. Along with resolution of post-acute COVID-19 symptoms, we noted resolution of SARS-CoV-2 antigen persistence determined by qPCR and confocal immunofluorescence in all 3 gut segments from 9 of 9 patients.

These findings indicated clearance of viral antigens from the gastrointestinal tract, which coincided with symptom resolution ~2 years after acute SARS-CoV-2 infection. Notably, patients with post-acute COVID-19 (similar to patients with antigen persistence) exhibited reduced serotonin serum concentration at first endoscopy when compared to patients without post-acute COVID-19 symptoms, and longitudinal analysis revealed that resolution of post-acute COVID-19 was associated with restoration of serum serotonin concentration.

The complete symptom resolution in all 32 patients exhibiting antigen persistence in our initial examination 10 did not allow us to explore patients with ongoing symptoms. Consequently, this study cannot determine whether ongoing postacute COVID-19 symptoms were associated with persistence of SARS-COV-2 antigens, which reflects a limitation of our study.

The window of gut mucosal antigen clearance (months to years) suggests that stem cells in the gut or bone marrow are affected, because most gut-resident immune cells exhibit a half-life of days to weeks. 19 As such, our study indicates that viral antigen clearance is associated with resolution of symptoms and serum serotonin restoration in post-acute COVID-19. The concept that SARS-CoV-2 antigen persistence contributes to post-acute COVID-19 warrants further clinical trials (e.g. NCT05595369). As we currently lack therapy for post-acute COVID-19, the spontaneous resolution gives hope for many patients suffering from this complex syndrome.

 

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In our initial cohort of 46 participants, serotonin concentrations were evaluated.

I couldn't find mention of serotonin in that paper. In this paper they report serum concentrations in ng/mL and methods says —

Serotonin concentrations were quantified by a commercial ELISA kit (#EEL006, Invitrogen, Waltham, MA), following the manufacturers protocol.

Serotonin measurement is not straightforward (in platelet poor plasma) as noted in Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration (2024, Journal of Inflammation Research) though that may not apply with the technique they used here?