Efficacy of Probiotics in the Treatment of Hospitalised Patients With Novel Coronavirus Infection
Condition: Coronavirus Infection
MeSH terms: Infections; Communicable Diseases; Coronavirus Infections
Study type: Interventional

Summary: 
      The treatment of the new coronavirus infection (COVID-19) and COVID-19-associated diarrhoea
      and liver injury remains challenging. Optimizing treatment approaches for COVID-19 remains an
      issue. It is assumed, that changes in composition of intestinal microbiota is closely related
      to a change in the regulation of the immune response in the lungs in patients with COVID-19.
      These gut microbiota changes in combination with antibiotic prescription during the treatment
      increase the risk of antibiotic-associated diarrhea and C. difficile infection as well as
      worse clinical outcomes in these patients. Probiotics are useful for restoring the human gut
      microbiome and increasing anti-inflammatory response also. Despite the variety of uses of
      probiotics, there is still insufficient data on the clinical efficacy of including probiotics
      in the treatment of patients with COVID-19 infection.
    

Detailed description: 
      A randomized controlled open-label study approved by the local ethical committee. The study
      included patients with COVID-19 admitted to the T.M. Tareev Clinic of Internal Diseases of
      I.M. Sechenov First Moscow State Medical University in whom the disease was confirmed using
      polymerase chain reaction on nasopharyngeal and oropharyngeal swabs to detect severe acute
      respiratory syndrome-related coronavirus 2 (SARS-COV-2). The study was conducted from
      December 2020 to March 2021 and included participants in the age range from 18 to 75 years.

      The exclusion criteria were age over 75 years or under 18 years, consumption of probiotics
      for 3 months prior to admission, history of intolerance to probiotics or their components,
      refusal to participate and sign informed consent, pregnancy or breastfeeding, cancer or
      mental illness, and severe renal (glomerular filtration rate less than 50 mL/min) or hepatic
      (equivalent to cirrhosis class B or C on the Child-Pugh scale) dysfunction at the time of
      admission.

      Patients who prematurely discontinued the consumption of probiotics for reasons not related
      to the development of side effects were excluded from the study.

      The patients were randomised to the probiotics group (PRO group) or the control group (CON
      group). Patients in the PRO group received probiotics containing ~109 colony forming units
      (CFU) of Lactobacillus rhamnosus PDV 1705, ~109 CFU of Bifidobacterium bifidum PDV 0903, ~109
      CFU of B. longum subsp. infantis PDV 1911, and ~109 CFU of B. longum PDV 2301 three times a
      day during the hospital stay but for no more than 14 days (PDV is the commercial letter
      designation of the bacterial strains). The end point of the trial was day 14 of
      hospitalisation or the day of the patient's discharge or death, whichever occurred earlier.

      The control group consisted of patients who did not receive probiotics. Patients in both the
      groups also received dexamethasone and antiviral (favipiravir and/or riamilovir),
      antibacterial, anticoagulant (enoxaparin in most cases; rivaroxaban and dabigatran were used
      much less frequently), and anticytokine (tocilizumab or/and olokizumab) drugs according to
      indications and contraindications.

      Death from any cause was considered the primary outcome. Duration of hospitalisation, total
      duration of the disease, incidence of admission to intensive care unit, need for oxygen
      support or mechanical ventilation, and changes in the values of key biomarkers were
      considered the main secondary outcomes. The duration of diarrhoea [loose or watery stools or
      an increase in the frequency of bowel movements (more than three times per day)] and
      incidence of hospital-acquired diarrhoea as well as the progression of pre-existing liver
      injury and onset of liver injury were considered additional secondary outcomes. Liver injury
      was determined through the presence of abnormalities in any of the main liver test findings
      (serum alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl
      transferase, total bilirubin, and albumin levels).

      The volume of the affected lungs was measured using chest computed tomography (CT); it
      included the sum of ground glass and consolidation volumes.

      Results are presented as the median [interquartile range]. The groups were compared using
      Mann-Whitney test for continuous data and chi-square test for categorical data. Wilcoxon test
      was used to assess the changes in continuous biomarker values. Mortality was assessed using
      the Kaplan-Meier estimator and Cox's test. A p value ≤0.05 was considered the criterion for
      significance. Statistical calculations were performed using "Statistica 10" soft (TIBCO
      Software inc, Palo Alto, CA)
    

Intervention name(s): Probiotics
Intervention type(s): Other
Intervention description(s): Probiotics (10^9 CFU of each strain: Lactobacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911 and Bifidobacterium longum PDV 2301) 3 times per day in addition to standard treatment regimen for 2 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Novel Coronavirus Infection; Probiotics; Lactobacillus; Bifidobacterium; Clinical outcomes; C.difficile; Diarrhea; Liver; mortality