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Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19
  1. Chun Chau Lawrence Cheung1,2,
  2. Denise Goh3,
  3. Xinru Lim3,
  4. Tracy Zhijun Tien3,
  5. Jeffrey Chun Tatt Lim3,
  6. Justina Nadia Lee3,
  7. Benedict Tan3,
  8. Zhi En Amos Tay1,
  9. Wei Yee Wan4,
  10. Eileen Xueqin Chen1,
  11. Sanjna Nilesh Nerurkar5,
  12. Shihleone Loong1,
  13. Peng Chung Cheow6,
  14. Chung Yip Chan6,
  15. Ye Xin Koh6,
  16. Thuan Tong Tan7,
  17. Shirin Kalimuddin2,7,
  18. Wai Meng David Tai8,
  19. Jia Lin Ng2,9,
  20. Jenny Guek-Hong Low2,7,
  21. Joe Yeong1,3,
  22. Kiat Hon Lim1,2
  1. 1Department of Anatomical Pathology, Singapore General Hospital, Singapore
  2. 2Duke-NUS Medical School, Singapore
  3. 3Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore
  4. 4Department of Microbiology, Singapore General Hospital, Singapore
  5. 5Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  6. 6Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
  7. 7Department of Infectious Diseases, Singapore General Hospital, Singapore
  8. 8National Cancer Centre Singapore, Singapore
  9. 9Department of Colorectal Surgery, Singapore General Hospital, Singapore
  1. Correspondence to Dr Joe Yeong, Department of Anatomical Pathology, Singapore General Hospital, Singapore 169608, Singapore; yeongps{at}

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We read with great interest the article published by Zuo et al, which highlighted the presence of SARS-CoV-2 RNA in stool samples during active and convalescence phases of COVID-19 infection.1 However, no study has reported the presence of viral antigens within GI and hepatic organs during the convalescent phase.

Using conventional immunohistochemistry, we detected SARS-CoV-2 nucleocapsid protein (NP) in the colon, appendix, ileum, haemorrhoid, liver, gallbladder and lymph nodes (figure 1A–K) from five patients who recovered from COVID-19, ranging from 9 to 180 days after testing negative for SARS-CoV-2 (online supplemental table 1). Notably, when multiple tissues were obtained from one patient (patients 1 and 4), all the tissues showed the presence of the viral antigen, suggesting widespread multiorgan involvement of the viral infection. Interestingly, for the colon, the viral antigen was only present in normal colonic crypts and polyps but not in the neoplastic tissues (figure 1Q). Similar negative staining in the hepatocellular carcinoma tumour region was also observed (figure 1R) albeit the positive staining in some of the scattered immune cells (figure 1D). Validating our findings, we detected SARS-CoV-2 spike protein (figure 1L–P) and RNA (figure 2B–F) in the above-mentioned tissues using conventional immunohistochemistry and RNAscope, respectively. However, we were unable to detect viral RNA in some patients’ tissues (online supplemental table 1), possibly because of higher RNA degradation rate as compared with protein and other patient-dependent factors such as disease severity, time since recovery and basal metabolic rate.

Supplemental material


Figure 1

Immunohistochemical staining of the SARS-CoV-2 nucleocapsid and spike proteins in intestinal and hepatic tissues. (A and B) Positive SARS-CoV-2 nucleocapsid protein (NP) staining in colonic crypts (A) and appendix (B), both with a granular supranuclear cytoplasmic pattern. (C) positive SARS-CoV-2 NP staining in scattered immune cells …

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  • CCLC, DG and XL contributed equally.

  • Presented at Part of the work has been published in the preprint server MedRxiv. DOI:10.1101/2020.10.28.20219014

  • Contributors Conception, design and supervision: JY and KHL. Drafting of the article: CCLC, DG, XL and JY. Providing information of the patients: ZEAT, WYW, PCC, CYC, YXK, TTT, SK, WMDT and JG-HL. Assistance with histology-related techniques: TZT, JCTL, JNL and BT. Performing RT-PCR experiments: EXC. Conducting flow cytometry experiments: XL. Generating figures: CCLC, DG, XL and SNN. Providing scientific input from the pathology perspective: SL. All authors have read and agreed to the published version of the manuscript.

  • Funding The authors received funding from the Centre Grant of Singapore General Hospital (grant no. NMRC/CG/M011/2017_SGH) and A*STAR Career Development Award (202D8226).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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