ARS-CoV-2 PERSISTS IN INTESTINAL ENTEROCYTES UP TO 7 MONTHS AFTER SYMPTOM RESOLUTION
Tuesday, Mar 9, 2021
Authors:
Minami Tokuyama1, Mark S. Ladinsky2, Divya Jha1, Francesca Cossarini1, Alexandra E. Livanos1, Jason Reidy1, Michael Tankelevich1, Gustavo Martinez-Delgado1, Pamela J. Bjorkman2, Saurabh Mehandru1
Institutions:
1Icahn School of Medicine at Mt Sinai, New York, NY, USA, 2California Institute of Technology, Pasadena, CA, USA
Background:
Host proteins ACE-2 and TMPRSS2 facilitate SARS-COV-2 infection and are expressed in the lungs as well as the intestinal tract, particularly in the small bowel. Gastrointestinal symptoms represent the most common extrapulmonary manifestation of COVID-19. Viral RNA has been isolated from fecal samples from COVID-19 patients, where it can persist longer than detection in nasopharyngeal swabs. While SARS-CoV-2 infection of enterocytes has been demonstrated in vitro, in vivo studies are lacking.
Methods:
Small intestinal biopsies from patients who underwent clinically indicated endoscopic procedures after a positive SARS-COV-2 nasopharyngeal swab (n=27) or were found to have positive serology (n=2) were analyzed by immunofluorescence (IF) (n=25) and electron microscopy (EM) (n=14) for the presence of virus. Clinical details were also collected.
Results:
Sixteen of 29 patients had detectable SARS-CoV-2 antigen by either IF or EM (Figure 1). Virus was restricted to the epithelium and patchy in distribution. Virus was detected as soon as 15 days after symptom onset and persisted up to 6 months after symptom resolution. Five patients were nasopharyngeal swab positive at the time of procedure and, of these, 4 had detectable antigen on biopsy. Despite the presence of virus, only 9/16 patients had any signs of inflammation on histology, and when present, this was mild. In two patients where virus was present at 3 months and 4 months, additional biopsies were obtained at 7 months and 6 months, respectively. Viral antigen was persistently detected in both patients and both patients were nasopharyngeal swab negative for all procedures. Interestingly, only 37.5% (6 of 16) of patients with virus detected in the small bowel had GI symptoms (diarrhea, nausea or vomiting) during their acute COVID-19 illness as compared to 46.1% (6/13) of patients where no virus could be detected in the intestines.
Conclusion:
SARS-COV-2 infects enterocytes in humans in vivo and can persist in the intestines up to 7 months following symptoms resolution. This persistence is not associated with an overt inflammatory infiltrate and does not appear to correlate with presence of GI symptoms in the acute COVID-19 setting.
