ABSTRACT
The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5-10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system's hyperresponsiveness and a severe inflammatory condition (collectively referred as "cytokine storm") are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.
ABSTRACT
The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response;(ii) the fact that 5–10% of the patients present gastrointestinal symptoms;and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system’s hyperresponsiveness and a severe inflammatory condition (collectively referred as “cytokine storm”) are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.
ABSTRACT
Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients present a complex clinical picture that, in severe cases, evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. The underlying pathophysiological mechanisms are complex and multifactorial and have been summarized as a hyperresponse of the immune system that originates an inflammatory/cytokine storm. In elderly patients, particularly in those with pre-existing cardiovascular, metabolic, renal, and pulmonary disorders, the disease is particularly severe, causing prolonged hospitalization at intensive care units (ICU) and an increased mortality rate. Curiously, the same populations have been described as more prone to a gut microbiota (GM) dysbiosis profile. Intestinal microflora plays a major role in many metabolic and immune functions of the host, including to educate and strengthen the immune system to fight infections, namely of viral origin. Notably, recent studies suggest the existence of GM dysbiosis in COVID-19 patients. This review article highlights the interplay between the triad GM dysbiosis-immune hyperresponse-inflammation in the individual resilience/fragility to SARS-CoV-2 infection and presents the putative impact of pharmacological and nutraceutical approaches on the triumvirate, with focus on GM.
ABSTRACT
Coronavirus disease 19 (COVID-19) is a pandemic condition caused by the new coronavirus SARS-CoV-2. The typical symptoms are fever, cough, shortness of breath, evolving to a clinical picture of pneumonia and, ultimately, death. Nausea and diarrhea are equally frequent, suggesting viral infection or transmission via the gastrointestinal-enteric system. SARS-CoV-2 infects human cells by using angiotensin converting enzyme 2 (ACE2) as a receptor, which is cleaved by transmembrane proteases during host cells infection, thus reducing its activities. ACE2 is a relevant player in the renin-angiotensin system (RAS), counterbalancing the deleterious effects of angiotensin II. Furthermore, intestinal ACE2 functions as a chaperone for the aminoacid transporter B0AT1. It has been suggested that B0AT1/ACE2 complex in the intestinal epithelium regulates gut microbiota (GM) composition and function, with important repercussions on local and systemic immune responses against pathogenic agents, namely virus. Notably, productive infection of SARS-CoV-2 in ACE2+ mature human enterocytes and patients' GM dysbiosis was recently demonstrated. This review outlines the evidence linking abnormal ACE2 functions with the poor outcomes (higher disease severity and mortality rate) in COVID-19 patients with pre-existing age-related comorbidities and addresses a possible role for GM dysbiosis. The article culminates with the therapeutics opportunities based on these pathways.