A recent article published in Cell Death Discovery has explored digestive symptoms of COVID-19 and the potentially pathogenic route of SARS-CoV-2 infection in digestive tract organs.
Researchers have established that SARS-CoV-2 invades the host cell by binding to the transmembrane receptor Angiotensin-converting enzyme 2 (ACE2). As ACE2 plays a critical role in cellular entry, it means ACE2-positive cells are susceptible to infection. Therefore, the expression of ACE2 may impact the virus invasion path and pathogenicity.
The most common symptoms of coronavirus include fever, fatigue, cough, myalgia and dyspnoea. Other individuals may also suffer from digestive symptoms including diarrhoea, nausea, vomiting and pharyngalgia. The presentation of these symptoms suggests that digestive tract organs may be a key target of the virus. ACE2 expression has been reported in some organs, such as the lung, kidney and oral mucosa; however, there is little information about its expression in the entire digestive tract (from oral cavity to the gastrointestinal tract).
In this study, researchers from the Sun Yat-sen University in China investigated the digestive symptoms of 48 COVID-19 positive patients from Guangzhou Eighth People’s Hospital. They also explored ACE2 expression in digestive tract cancers and lung cancers from a series of bulk tissue and single-cell RNA sequencing (RNA-Seq) data from public databases.
The team found that 25% (12/48) of patients suffered from digestive symptoms, with pharyngalgia being the most common manifestation (7/48). The bulk tissue RNA-Seq analysis highlighted that organs within the digestive tract had increased ACE2 expression compared to the lung. In addition, results from single-cell RNA-Seq revealed that the ACE2-positive-cell ratio in digestive tract organs was significantly higher compared to in the lung. The team discovered that the expression of ACE2 in the lung increased with age. Interestingly, they also found that tumour cells had a higher expression of ACE2 compared to normal control tissues. Furthermore, expression of ACE2 in gastric tissues gradually increased with histological grading – from chronic gastritis to intestinal metaplasia, to early gastric cancer.
This study has provided evidence to suggest that the digestive tract organs should be considered vulnerable targets for SARS-CoV-2 infection. It has also emphasised that cancer patients may be more susceptible to SARS-CoV-2 infection, a recurrent theme in current studies.