Identification of Persistent Sars-Ncov-2 Viral Presence in the Intestines of Multiple Pediatric Patients Suggests Possible Common Etiology of Gi Long Covid

ABSTRACT

Background: The phenomenon known as "Long Covid," (LC) marked by post-infectious symptoms of a wide variety, and typically not associated with initial infectious severity, has the potential to become a tremendous public health burden as infections continue at a high rate. Variations of LC may impact over 80% of patients, with unclear pathogenesis, although many speculate that persistent viral presence in end-organ tissue may drive local changes. We previously published a case report noting persistent SARS-nCoV-2 activity in the cecum of a patient 3 months after initial infection (Arostegui et al, JPGN Reports, 2022). We have sought to expand that finding by assessing additional patients who have undergone endoscopic evaluation for presence of SARS-nCoV-2 nucleocapsid, seeking to expand our understanding of the clinical effects of persistent infection. Method(s) We identified 6 patients with onset of symptoms in the post-SARS-nCoV-2 window, who had undergone EGD/colonoscopy without histopathological diagnosis. New blank slides were cut and sent for staining at Histowiz inc (Brooklyn, NY), with rabbit monoclonal SARS-CoV-2 nucleocapsid antibody (GTX635686, 110,000). Resulting slides underwent blinded pathology review to identify positives. Chart review was completed on patients who were identified as positive, including histopathology data from endoscopy, medical history, presentation, laboratory results and clinical course. Result(s) Including our initial report, we have identified 4 female patients ages 11-16 to date. Viral presence was identified in the duodenum and TI, but only in one patient in the colon (cecum). Patients presented for evaluation of a variety of GI manifestations including chronic abdominal pain (100%), nausea and vomiting (50%), loss of appetite (50%), tenesmus (50%), hematochezia (25%) as well as weight loss (50%). Notably, of the 4 patients identified, only 1 had a known history of confirmed SARS-nCoV-2 infection. Endoscopic findings in the intestine were normal with the exception of edema noted in the cecum of two patients. Mucosal biopsies were also positive for notable (if typically felt to be non-pathologic) lymphoid aggregates in the Colon (75%) as well as in the Terminal Ileum (50%). Clinical information is summarized in Table 1. Conclusion(s) Additional identification of persistent SARS-nCoV-2 presence in patients ranging from 3-18 months after symptom onset demonstrates a high likelihood that persistent viral presence contributes to post-infectious symptoms in many patients. Patients demonstrated "red flag" symptoms like nighttime awakening with pain, weight loss, and elevated inflammatory markers or calprotectin, but symptomatically improved over time and with measures targeted at IBS. Our limited sample size prevents determination of typical location of persistent viral activity, but it is notable that symptoms for colonic vs. SI persistence were clinically consistent, with diarrhea in colonic persistence and early satiety/pain characterizing SI persistence. Most notably, we have identified a tendency for persistent infection to occur, potentially explaining at least a subset of persistent IBS-like symptoms associated with GI LC. Further work is necessary to determine exactly the prevalence of this issue, as well as to characterize the natural history of the clinical course, and possible effective therapies. (Table Presented).