Abstract
Background & aims: The coronavirus disease 2019 (COVID-19) pandemic has affected populations, societies, and lives for more than 2 years. Long-term sequelae of COVID-19, collectively termed the postacute COVID-19 syndrome, are rapidly emerging across the globe. Here, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen persistence underlies the postacute COVID-19 syndrome.
Methods: We performed an endoscopy study with 46 patients with inflammatory bowel disease (IBD) 219 days (range, 94-257) after a confirmed COVID-19 infection. SARS-CoV-2 antigen persistence was assessed in the small and large intestine using quantitative polymerase chain reaction of 4 viral transcripts, immunofluorescence of viral nucleocapsid, and virus cultivation from biopsy tissue. Postacute COVID-19 was assessed using a standardized questionnaire, and a systemic SARS-CoV-2 immune response was evaluated using flow cytometry and enzyme-linked immunosorbent assay at endoscopy. IBD activity was evaluated using clinical, biochemical, and endoscopic means.
Results: We report expression of SARS-CoV-2 RNA in the gut mucosa ∼7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8 + T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19, immunosuppressive therapy, and gut inflammation. We were unable to culture SARS-CoV-2 from gut tissue of patients with viral antigen persistence. Postacute sequelae of COVID-19 were reported from the majority of patients with viral antigen persistence, but not from patients without viral antigen persistence.
Conclusion: Our results indicate that SARS-CoV-2 antigen persistence in infected tissues serves as a basis for postacute COVID-19. The concept that viral antigen persistence instigates immune perturbation and postacute COVID-19 requires validation in controlled clinical trials.
Keywords: COVID-19; Postacute COVID-19; SARS-CoV-2; Viral Antigen Persistence.
【저자키워드】 COVID-19, SARS-CoV-2, Postacute COVID-19, Viral Antigen Persistence., 【초록키워드】 coronavirus disease, Inflammation, Coronavirus disease 2019, coronavirus, immune response, pandemic, therapy, T cells, severity, clinical trials, severe acute respiratory syndrome Coronavirus, CD8, flow cytometry, immune, nucleocapsid protein, Antigen, RNA, Inflammatory bowel disease, polymerase chain reaction, enzyme-linked immunosorbent assay, Stool, Culture, COVID-19 infection, nucleocapsid, persistence, endoscopy, intestine, Patient, Mild, SARS-CoV-2 RNA, SARS-CoV-2 antigen, immunofluorescence, virus cultivation, Quantitative, questionnaire, immunosuppressive therapy, IBD, SARS-CoV-2 antigens, immunosuppressive, Gut, Chain Reaction, Viral antigen, acute respiratory syndrome, large intestine, biochemical, acute respiratory syndrome coronavirus, tissue, acute respiratory syndrome coronavirus 2, enzyme, viral transcripts, syndrome, controlled clinical trials, Confirmed COVID-19 infection, acute COVID-19, quantitative polymerase chain reaction, viral nucleocapsid protein, populations, means, enzyme-linked immunosorbent, gut mucosa, polymerase chain, performed, affected, globe, reported, investigated, detectable, evaluated, majority, expression of SARS-CoV-2,