Gastrointestinal Manifestations in Covid-19

Covid-19 is caused by Severe Acute Respiratory Syndrome SARS-CoV-2 or novel Coronavirus. This is a  positive-sense single stranded RNA  virus. The mode of human to human transmission for Covid-19 virus is primarily through fomites, air droplets and aerosols. Presently airborne transmission is under study probably evolving in the transmission. The characteristic involvement of COVID-19 is of respiratory system. Fever, sore throat, cough, dyspnea, malaise, headache and myalgias or arthralgia are usual presenting symptoms in respiratory system involvement. Nearly 80 % of patients exhibit mild symptoms; 20 % have severe disease and approximately  5 % of patients demonstrate critical manifestations like respiratory failure, acute respiratory distress syndrme (ARDS) sepsis, or multiple organ dysfunction syndrome and sometimes death.

Gastrointestinal symptoms may be seen with COVID-19 infection. There are reports where few COVID-19 cases exhibit Gastrointestinal tract symptoms preceding respiratory signs symptoms. Some patients may present with Gastrointestinal tract symptomatology solely with the complete absence of respiratory system involvement. Present studies show prevalence  of gastrointestinal involvement in Covid-19 is as high as 50%, but most studies show ranges from 16% to 33%. The myriad of Gastrointestinal symptoms present in Covid-19 infection encompass diarrhea, loss of appetite, nausea or vomiting and abdominal pain. Anorexia is much more commonly reported than other symptoms, but since it is difficult to objectively assess, not considered as prime symptom. Patient may have single or present with multiple symptoms. Hepatic, pancreatic and gallbladder involvement has been documented in the Covid-19 infection. Gut perforation likely by Covid-19 is reported in literature. A high index of suspicion is required to clinically diagnose Covid-19 infection presenting with Gastrointestinal tract symptoms in high risk cases at earliest . High viral load shedding in the stool,intrinsic long viability on surfaces, lack of correlation with clinical symptomatology  makes easy potential of Covid-19 virus for human to human spread. A special mention is of “Toilet Plume”, aerosols generated from turbulence by flushing of toilet bowl, likely to fling Covid-19 aerosol.

Covid -19 is detected throughout the gastrointestinal tract, present on oesophagus, stomach, duodenum, small intestine and rectum. The receptor for attachment of Covid 19 virus is angiotensin-converting enzyme2(ACE-2). This ACE-2 receptor is present predominantly in type-2 alveolar cells in the lungs .In abdomen, this receptor is expressed abundantly in the glandular cells as well as in the enterocytes of the lining epithelium of stomach, duodenum, rectum,in cholangiocytes ,liver cells and pancreatic islets.Gallbladder show high expression of ACE2 in its glandular cells.In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a projection on its surface called the S-spike using the transmembrane serine protease 2(TMPRSS2)  catalysing the entry of virus into the host cells.The mechanism suggested for causation of diarrhea in COVID-19 infection involve damage to infected absorptive enterocytes  potentially leading to malabsorption, unbalanced intestinal secretion an activated enteric nervous system and dysbiosis. Abdominal pain, nausea and vomiting is significantly associated with increased COVID-19 severity.

Pro-inflammatory cytokine release storm by Covid-19 causes hypercoagulable state.This manifests  as generalized small-vessel vasculitis and extensive microthrombi due to local injury This morbid state, when associated with comorbidity like Diabetes, hypertension coronary disease and immunodeficiency disorders etc;,are associated with enormous risk of coagulation in an extensive tissue distribution.

Colon perforation reported in Gastrointestinal tract is directly or indirectly by ischemic changes due to septic and thromboembolic events induced by Covid-19 infection. Exploratory laparotomy for Covid-19 abdominal complications requiring intervention or the immediate postmortem findings of deceased show impaired visceral perfusion in the entire gastrointestinal tract, punctate lesions in the sigmoid colon,and rarely fecal peritonitis.Histopathology of the stomach, duodenum or rectum specimen show numerous infiltrating plasma cells and lymphocytes as well as interstitial oedema in the lamina propria of gut.

Liver-related transaminases are elevated as well as late cholestasis is frequently observed in  number  of Covid -19 patients. This is usually  mild enzymatic  elevation, resolves when the patient improves clinically.Covid-19 may lead to direct injury on hepatocytes,cholangiocyte dysfunction or hypoxic injury. A virus induced cytokine storm leads to liver dysfunction. Histopathological examination of liver specimen in  COVID-19 patients do not show viral inclusions in specimen .Presently till date , only 1 case of Gastrointestinal COVID-19 infection has been reported with features of acute liver failure.Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19 due to presence of ACE-2 receptors.Endoluminal obiletration of vessels ,inflammatory  infiltration ,hemmorhagic infarction and nerve hypertrophy of gallbladder are microscopic changes seen in Covid-19 infection.

Covid-19 viral adherence on ACE-2 receptors on pancreatic islets cause` acute elevated in serum glucose,cytokine storm with added drug induced pancreatic injury. Serum pancreatic enzyme rise have been reported, defined by an elevated serum amylase or lipase.No case of severe pancreatitis occurring by  Covid-19 has been reported yet.Those who  had pancreatic injury by Covid-19 are associated with higher incidence of anorexia and diarrhea and more severe illness.

COVID Infection Concomitant with Inflammatory Bowel Disease (IBD) is to be considered. If exposed to Covid-19 infection, pre-existing bowel related autoimmune disease like  inflammatory bowel disease or other conditions may progress to  severe disease. ACE-2 receptor has increased tissue concentration in the inflamed mucosa of patients with active ulcerative colitis and Crohn’s disease.The serine protease level, the key primer to activate S-protein is 10 times higher in patients with inflammatory bowel disease than others.These  factors contribute to enhanced viral adherence to the mucosal lining  and greater  risk of Covid-19 infection with worse prognosis.

Approximately 50% of patients with COVID-19 demonstrate detectable viral RNA in the stool as well as on anorectal swabs.Test of SARS-CoV-2 virus in stool has been found to be positive even after a negative nasopharyngeal swab test in 42.9%–81.8% of cases.The fecal-oral transmission has not been confirmed definitively despite evidence of viral replication and shedding of Covid-19 virus in stool.The occurrence of gastrointestinal manifestation is paving way to enhance utilisation of fecal nucleic acid(viral RNA) tests to diagnose COVID-19 .Management of Gastrointestinal symptoms is mainly conservative with the effective  Covid-19 infection control. Patients should be advised to use sanitisers,use of masks practice, proper hand hygiene and maintain social  distancing as well as physical distancing.

Dr Imtiaz Ahmed Wani is Consultant Surgeon, Directorate of Health Services, Kashmir