COVID-19 News: Emerging Studies Shows SARS-CoV-2 Attacks The Digestive Tract Especially The Intestines Directly, Reported Case Of Bowel Perforation

COVID-19-News: Initial hypothesis that the it was the cytokine storms as a result of SARS-Cov-2 infections that were destroying various organ tissues including the heart, kidneys, intestines and even brain tissues are now being replaced with the stark fact it is actually the SARS-CoV-2 coronavirus itself that is causing these issues and in some cases it might be also compounded by the inflammatory responses.



The digestive tract has already been known to be affected as even stools were found to be carry infectious viral loads of the SARS-CoV-2 coronavirus.
 
Various studies have shown that the alimentary canal especially the intestines are extremely rich in ACE2 receptors and CD147 receptors, both binding targets of the SARS-CoV-2 coronavirus. (Vabret et al. 2020)
 
In the first study by Chinese researchers from West China Hospital-Sichuan University, 25 patients with COVID-19 and 13 with suspect COVID-19 were studied in detail including various biomarkers and also intestinal tissue samples
 
Their findings which are published on a preprint server(not peer-reviewed yet) found that the intestines were attacked by the SARS-CoV-2 coronavirus which resulted in acute inflammation. https://www.researchsquare.com/article/rs-56005/v2
 
Interestingly the researchers found that when the intestines and other parts of the alimentary canal was infected, the patients did not experience a immune dysregulation suggesting that involvement of alimentary system may provide protection through competitive inhibition and anti-inflammatory mechanism.
 
The study team found a soluble form of ACE2 that lacks the membrane anchor and partly circulates in blood can be produced by proteolytic cleavage. It has been proposed that the soluble form of ACE2 competitively inhibits the cellular full-length ACE2 protein so that SARS-COV is sequestrated, limiting infective progression and reducing susceptibility to further infection
 
Also interestingly is the discovery that the cleavage of ACE2 into the soluble form is mediated by the ADAM17, a TNF-α convertase upregulated in patients with gastrointestinal injury or inflammation. Moreover, ACE2 has been demonstrated to participate in reninangiotensin-aldosterone system (RAAS) that includes the classical ACE2/Ang 1–7/MAS-1 receptor (MAS1-R)
 
Past studies have suggested that ACE2/MasR system plays a critical role in numerous anti-inflammatory pathways regulating tissue protection. https://www.nature.com/articles/nature11228
 
In another study by Italian researchers from Università degli Studi di Pavia at Lombardy, it was found that as a result of intestinal attack by the SARS-CoV-2, a patient suffered necrotizing vasculitis leading to pseudomembranous colitis and a perforated bowel. https://www.researchsquare.com/article/rs-79258/v1
 
The Italian researchers reported that a 73-years-old man came into emergency department with 24‐hour history of fever and progressive dyspnoea. His remote medical history revealed ischemic heart disease, hypertension, NIDDM and mild chronic renal impairment. At physical examination he presented lower limbs edema, dyspnea, 37.3°C temperature, arterial hypertension, sinus rhythm at 85 bpm and a peripheral oxygen saturation of 94% in spontaneous breathing in air. No abdominal symptoms were reported. Anteroposterior chest X-ray shows right basal consolidation and bilateral lung congestion.
 
A nasopharyngeal swab specimen for COVID-19 collected, reported back as negative. The patient was admitted in a General Medicine ward with the diagnosis of COVID-19 negative pneumonia leading to heart failure and pulmonary edema. Antibiotics (ceftriaxone and azithromycin), diuretics and continuous positive airway pressure (CPAP) ventilation has been started. Ten days after, a worsening of respiratory involvement despite treatment, and typical radiological findings leads to perform a second nasopharyngeal swab specimen for testing COVID-19 which came back positive. The patient was transferred to a cohort isolation ward and hydroxychloroquine administration and LMWH treatment have been started, CPAP ventilation and antibiotic therapy (azithromycin only) were continued.
 
However the patient developed fever and profuse diarrhea without vomiting and on physical examination, it was found that the abdomen was treatable but widely painful and distended. After collecting urine and blood samples, empirical antibiotic therapy with Piperacillin/tazobactam aas been started. Laboratory tests show normal WBC count and formula and normal PCT level, while RCP and D-Dimer levels are elevated. Given the patient’s clinical progressive worsening, an abdominal CT scan was performed and it showed a 10 cm caudo-cranial extended parietal thickening of the ascending cecum-colon and intraperitoneal free air collection.  
 
Hence, emergency surgery was been performed, leading to right hemicolectomy for bowel perforation. After surgery, the patient was admitted to ICU both to treat COVID-19 related respiratory failure and to perform postoperative care.
 
The anatomopathological examination of the surgical sample revealed a pseudomembranous colitis with masses of mucus and neutrophilic granulocytes, present from the ileocecal valve to part of the ascending colon. However, a vast oedema, acute inflammation and foci of necrotizing vasculitis, with fibrin thrombi and abundant infiltration of intravascular neutrophilic granulocytes was been identified. Given the typical presentation and  the long hospitalisation and the risks factors, samples for Clostridium Difficile toxins research was collected both from ileostomy and from stool from rectal ampule, with negative results. A PCR test for SARS-CoV-2 isolation was performed for gastric fluid, which came back positive. After improvement of clinical conditions, in day 24, the patient was discharged from ICU to a low intensity ward.


ACE2 Expression in Organs and Systems Most Frequently Implicated in COVID-19 128
Complications. Source: Vabret et al. (2020)
 
The study team describes a possible critical complication of the still largely unknown disease related to SARS-CoV-2 infection. Many COVID-19 patients present GI symptoms together with respiratory ones. They said that Gastro-enteric involvement may be due to enteric virus replication. Necrotizing vasculitis is a histopathological pattern commonly found in COVID-19 patients in several organs. Clostridium difficile negative pseudomembranous colitis due to a necrotizing vasculitis, in this case, may be a SARS-CoV-2 infection complication too.
 
The team warned that such manifestations might be more common that thought and suggest that more clinical investigations are done fast when patients admitted are reporting similar symptoms or condition.
 
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