The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19
Condition: Berberine; COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Berberine; Montmorrillonite
Intervention type(s): Drug; Drug
Intervention description(s): Patients in the intervention group received berberine daily, regardless of gastrointestinal symptoms.If the patient has a serious drug-related adverse event, the drug will be discontinued and the patient will be excluded from the study.; Patients in the control group were routinely not given special treatment.However, if the patient has diarrhea symptoms, montmorillonite powder should be given orally.
Other intervention name(s): Berberine Hydrochloride Tablets; Montmorrillonite Powder
Intervention MeSH terms: Bentonite
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Gastrointestinal function; inflammatory biomarkers; Organ function