The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19
The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19
Coronavirus disease 2019 (COVID-19) rapidly spread across China and throughout the world,
 causing hundreds of thousands died. Studies had shown that "cytokine storms" and subsequent
 multiple organ dysfunction (MODS) are important causes for disease progression and death in
 patients with COVID-19. Similar to SARS-CoV infection, SARS-CoV-2 would infect humans via
 binding of S-protein to angiotensin-converting enzyme 2 (ACE2), a host cell receptor, and the
 S protein is activated and cleaved by cellular transmembrane serine proteases, allowing the
 virus to release fusion peptides for membrane fusion. In addition to the lungs, ACE2 is also
 highly expressed in the esophagus, small intestine and colon, suggesting that the gut might
 also be an important target organ for SARS-CoV-2. About 8-16% of severe pneumonia cases
 confirmed with SARS-CoV-2 infection developed gastrointestinal symptoms such as abdominal
 pain, vomiting, and diarrhea. Moreover, the stool of patient with COVID-19 also positive by
 real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Furthermore,
 elevated faecal calprotectin was observed in patients with COVID-19 suggested an inflammatory
 response in the gut, which was significantly correlated with IL-6. For severe and critical
 cases, control "cytokine storms" and maintain intestinal microenvironment balance have been
 included into the Diagnosis and Treatment Guideline of patients with COVID-19 (Edition 7).
 Berberine is a quaternary ammonium alkaloid isolated from rhizoma coptidis. It is often used
 in treatment of infectious diarrhea by bacteriostasis and inhibition of intestinal gland
 secretion. Berberine has also been found to have a role in intestinal immune regulation,
 inhibiting both AP-1 and NF- B, the key factors in cell signal transduction, and reducing the
 inflammatory response. Investigators conducted a prospective randomized controlled clinical
 trial to investigate the effects of berberine on intestinal function, serum concentrations of
 the inflammatory biomarkers, and organ function in severe patients with SARS-CoV-2 infection.
Patients aged 18-80 years who confirmed with COVID-19 and classified as severe were enrolled
 in the study, and then separated randomly into two groups: a berberine group (B group) and a
 control group (C group). The diagnostic criteria for severe cases are in accordance with the
 Diagnosis and Treatment Guideline of patients with COVID-19 issued by the National Health
 Commission of the People's Republic of China (Edition 7). In general, patients diagnosed with
 COVID-19 pneumonia must also meet any of the following criteria: appears shortness of breath,
 respiratory rate (RR) ≥ 30 times/min; SPO2 ≤ 93% at rest; the ratio of partial oxygen
 pressure of arterial blood (PaO2) to oxygen absorption concentration (FiO2) ≤ 300mmHg
 (1mmHg=0.133KPa); pulmonary imaging showed the lesion progression >50% within 24-48 hours.
 All enrolled patients were given general support therapy, oxygen therapy, antiviral drugs, in
 combination with antibiotics and small doses of glucocorticoids if necessary, nutritional and
 organ function support. Patients in the berberine group (B group) were given berberine 0.3g
 tid orally or tube feed daily, while patients in the control group (C group) were given
 montmorilonite orally if they presence of diarrhea. The duration of the study intervention
 was 14 days and followed up to discharge. Investigators record general information about
 patients at admission, including age, gender, age, exposure history, time from onset of
 symptoms to hospital, APACHE II score, the presentation of X-ray, comorbidity, mechanical
 ventilation, fever or not,gastrointestinal symptoms. Investigators also evaluate the
 gastrointestinal function daily,including gastrointestinal symptoms (nausea, vomiting,
 abdominal pain, abdominal distension or diarrhoea), frequency of diarrhea, the
 characteristics of stool (Bristol scal). Peripheral blood are collected on day 1,3, 7 and 14
 after admission to determine the level of interleukin-6 (IL-6), interleukin-1β (IL-1β),
 interleukin-10 (IL-10) and tumor necrosis factor (TNF-α). Laboratory tests are also performed
 to evaluate leucocyte, c-reactive protein (CRP), and procalcitonin (PCT) levels at the same
 time. Glutamate transaminase (ALT), glutamate transaminase (AST), urea nitrogen (Bun),
 creatinine, prothrombin time (PT), partially activated prothrombin time (APTT), and
 Sequential Organ Failure Assessment (SOFA) score are used to evaluate organ function on day
 1,3, 7 and 14 after admission. Investigators also record the adverse events associated with
 the drug, length of stay and the prognosis at discharge. The patients are blinded to the
 group allocation. Two physicians are responsible for data processing, one is responsible for
 recording and collecting, and the other is responsible for checking, and they are all blind
 to the research.
Inclusion Criteria:

 -  Patients confirmed with COVID-19 and classified as severe

 Exclusion Criteria:

 -  inflammatory bowel disease;

 -  have other sources of infection;

 -  death is anticipate within 72 hours;

 -  participated in other clinical trials;

 -  pregnant or lactating women;