SARS CoV-2 Organotropism Associated Pathogenic Relationship of Gut-Brain Axis and Illness

Abstract

COVID-19 has resulted in a pandemic after its first appearance in a pneumonia patient in China in early December 2019. As per WHO, this global outbreak of novel COVID-19 has resulted in 28,329,790 laboratory-confirmed cases and 911,877 deaths which have been reported from 210 countries as on 12th Sep 2020. The major symptoms at the beginning of COVID-19 are fever (98%), tussis (76%), sore throat (17%), rhinorrhea (2%), chest pain (2%), and myalgia or fatigue (44%). Furthermore, acute respiratory distress syndrome (61.1%), cardiac dysrhythmia (44.4%), shock (30.6%), hemoptysis (5%), stroke (5%), acute cardiac injury (12%), acute kidney injury (36.6%), dermatological symptoms with maculopapular exanthema (36.1%), and death can occur in severe cases. Even though human coronavirus (CoV) is mainly responsible for the infections of the respiratory tract, some studies have shown CoV (in case of Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) to possess potential to spread to extra-pulmonary organs including the nervous system as well as gastrointestinal tract (GIT). Patients infected with COVID-19 have also shown symptoms associated with neurological and enteric infection like disorders related to smell/taste, loss of appetite, nausea, emesis, diarrhea, and pain in the abdomen. In the present review, we attempt to evaluate the understanding of basic mechanisms involved in clinical manifestations of COVID-19, mainly focusing on interaction of COVID-19 with gut-brain axis. This review combines both biological characteristics of the virus and its clinical manifestations in order to comprehend an insight into the fundamental potential mechanisms of COVID-19 virus infection, and thus endorse in the advancement of prophylactic and treatment strategies.

A cohort autopsy study defines COVID-19 systemic pathogenesis

“…Investigations of SARS-CoV-2 organotropism, its duration in the target organs and the correlation with disease progression are pivotal for developing effective strategies for the containment of the pandemic. Some studies revealed SARS-CoV-2 distribution in human tissues and viral shedding in body fluids, 18,[35][36][37][38] but the translational significance remains unclear. Our pathological evidence of SARS-CoV-2 presence in late stage of critically ill patients with COVID-19 suggests that continued usage of antiviral therapy is indispensable throughout the disease course.…”

COVID-19 and the digestive system: A comprehensive review

“…However, recent studies have revealed that SARS-CoV-2 infection can alter the intestinal microbiota in COVID-19 patients, characterized by the enrichment of pathogenic microbes and opportunistic pathogens, resulting in gut dysbiosis[ 100 - 105 ]. As described previously, the absorption of tryptophan is associated with neurological abnormities, as it is the precursor for the synthesis of 5-hydroxytryptophan in the brain[ 103 ]. It also regulates the levels of antimicrobial peptides that affect the composition of the gut microbiota, leading to increased sensitivity to intestinal inflammation and epithelial dysfunction[ 106 ].…”

“…It also regulates the levels of antimicrobial peptides that affect the composition of the gut microbiota, leading to increased sensitivity to intestinal inflammation and epithelial dysfunction[ 106 ]. Thus, this viral infection might affect the homeostasis of the gut-brain axis through the intestinal microbiota[ 103 , 107 ]. However, further investigations are needed to clarify whether the dysbiosis is specific to SARS-CoV-2 infection or a consequence of critical illness.…”

The Role of the Gastrointestinal System in Neuroinvasion by SARS-CoV-2

“…The human intestinal tract, the niche of a large number of intestinal microflora, is mainly dominated by Firmicutes and Bacteroides, which produce a variety of metabolites to maintain intestinal homeostasis (Foster and McVey Neufeld, 2013). Intestinal microflora can affect immune functions such as the production of acetate and butyrate and protection from respiratory virus infection; changes in the intestinal microflora may induce behavioral changes, leading to depression and confusion (Dinan et al, 2015;Dhar and Mohanty, 2020;Shinu et al, 2020).…”