Abstract
The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.
Highlights
In December 2019, the disease known as Coronavirus Disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported for the first time and has been claimed over three and a half million lives around the world[1].COVID-19 is mainly characterized by symptoms caused by a viral infection of the upper airways and the lung such as fever, cough, dyspnea, anosmia, and fatigue[2]
Small intestinal reaction in COVID-19 patients To evaluate the macroscopic and histomorphologic changes in the duodenum of COVID-19 patients, duodenal biopsies were taken by esophagogastroduodenoscopy
While some affected organs were tested positive for SARS-CoV-24–6, others showed histopathological changes but did not show active viral replication as no SARS-CoV2 RNA could be detected within these organs[6,7,32]
Summary
In December 2019, the disease known as Coronavirus Disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported for the first time and has been claimed over three and a half million lives around the world[1].COVID-19 is mainly characterized by symptoms caused by a viral infection of the upper airways and the lung such as fever, cough, dyspnea, anosmia, and fatigue[2]. (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported for the first time and has been claimed over three and a half million lives around the world[1]. An increasing number of reports indicate that COVID-19 is more of systemic nature, including cardiovascular, haematological, renal, neurologic, and dermatologic as well as gastrointestinal manifestations[3]. To date it remains unknown, whether these effects are caused by direct SARS-CoV-2 infection of the respective tissues[4,5,6,7], indirectly by the excessive release of cytokines[8], by thromboembolic effects impairing microcirculation[3], or by a combination of all mentioned complications. SARS-CoV-2 RNA was shown to be present in feces and in esophageal, Received: 18 February 2021 Revised: 1 July 2021 Accepted: 2 August 2021 Published online: 21 August 2021
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