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SARS-CoV-2 RNA and antigens were detected in the appendix, skin and breast of two patients with long COVID syndrome (case report)

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a new disease, known as post-acute sequelae of SARS-CoV-2 infection or long COVID syndrome. Although this disease is more common in hospitalization survivors, even those who have experienced mild acute COVID-19 have a wide range of organ dysfunction and clinical symptoms. In this study, the authors from Singapore and Spain investigated the presence of SARS-CoV-2 RNA and antigens in tissue specimens obtained from two patients diagnosed with long COVID syndrome. 

Although patients who developed a long COVID syndrome often test negative for SARS-CoV-2, numerous studies reported the persistence of viral RNA and/or antigen(s) in tissue specimens, especially from the gastrointestinal (GI) tract. The same research group reported before the persistence of SARS-CoV-2 RNA and specific viral antigens for up to 180 days in the GI of COVID-19 convalescents who did not develop long COVID syndrome. The GI tract is considered a potential viral reservoir for SARS-CoV-2 and a major viral shedding route.

A recent study has shown that the virus present in the intestinal lumen could damage the intestinal epithelial barrier, enter the blood vessels, and spread to various organs. The infection of the intestinal cells with the SARS-CoV-2 at the apical side (not at the basolateral side) resulted in severe damage to the integrity of the intestinal epithelial barrier.   https://discovermednews.com/sars-cov-2-infection-of-the-intestinal-cells-at-the-apical-side/

 

 

Case 1

A 44-year-old woman presented with fever, pharyngitis, bronchospasm, dysphagia, loss of smell and taste, anorexia, expectoration, headache, nausea and diarrhea, and weight loss. She was diagnosed with COVID-19 via serological testing. After two months she tested negative for SARS-CoV-2 with a polymerase chain reaction (PCR) test, but her symptoms persisted.

During the next months, the patient developed various symptomatology of long COVID syndrome, like chronic fatigue, headaches, dizziness, “brain fog”, loss of spatial orientation, myalgia, bronchospasm, reactive sinus tachycardia after minimal effort, inflammatory bowel disease, tongue inflammation, recurrent pharyngitis, tinnitus, and skin flare-ups.

After a year, the patient presented with generalized abdominal pain, loss of appetite, and nausea, and a laparotomy and appendectomy were performed urgently. She tested negative for SARS-CoV-2 before the surgery. The appendix sample and skin sample from her leg were taken for further examination 426 days after the onset of COVID-19. Histologic examination showed reactive lymphoid hyperplasia in the appendix and superficial and deep perivascular dermatitis in the skin tissue.

SARS-CoV-2 specific antigens, spike (S), and nucleocapsid (N) proteins were detected in the appendix tissue and co-localized with the myeloid and macrophage markers CD68, CD14, CD206, and CD169. Viral RNA was detected in the extracellular and intracellular space of the appendix. SARS-CoV-2 N protein was also detected in the skin macrophages.

 

Case 2

A 45-year-old woman with ductal carcinoma in situ presented with intensive headache, upper stomach pain, nausea, diarrhea, myalgia, and fatigue. She was diagnosed with COVID-19 by polymerase chain reaction (PCR) test for SARS-CoV-2.

After two months, she tested negative on a PCR for SARS-CoV-2. However, she developed various symptoms of post-acute COVID-19, including headaches, mental confusion, dysarthria, sleep disorder, lack of concentration, dyspnoea, tachycardia, stomachache, loss of appetite, pain in the liver and spleen area, arthralgia, and spontaneous bruises.

Six months after the onset of COVID-19 she underwent partial breast resection and margin control surgery. She tested negative for SARS-CoV-2 before the surgery. The breast tissue sample was taken 175 days after the onset of initial symptoms of COVID-19. SARS-CoV-2 N and S proteins were detected in the tumor-adjacent area and co-localized with the myeloid and macrophage markers CD68, CD14, CD206, and CD169. Viral RNA was detected in the extracellular and intracellular space of the breast tissue. 

 

 

Conclusion

This study has shown that SARS-CoV-2 RNA, nucleocapsid, and spike proteins were detected in GI and non-GI tissues (appendix, skin, and breast tissues) of two patients diagnosed with long COVID syndrome, 426 and 175 days after the onset of COVID-19. 

The authors emphasized a need for further investigation into the susceptibility of immunocompromised cancer patients to persistent viral replication and long COVID syndrome.  

 

This article was published in the Frontiers of Immunology

Journal Reference

Joseph CR, Edwards SG, Neo ZW, et al. Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID. Front. Immunol. 2022; 13: 939989.  https://doi.org/10.3389/fimmu.2022.939989

 

 

 

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