Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection

A Two-arm, Double-blind, Randomized, Placebo-controlled Trial Investigating the Efficacy of the Probiotic Dietary Supplement SmartProbio C in the Supportive Supplementation of Patients With a Complicated Course of COVID-19 Infection

The aim of the study is to test the efficacy of the probiotic SmartProbio C in patients with a severe course of COVID-19 infection. Patients were randomly divided into two arms between the probiotic group and the placebo group. They were further divided into four groups according to 1) BMI (Body mass index; <=30/>30), 2) age (<=65/>65), 3) CRP (C-reactive protein; <=100/>100), 4) chronic lung disease (yes/no). Gut microbiome analysis and its changes in selected parameters (amount of lactobacilli, bifidobacteria, Akkermansia, Proteobacteria, Firmicutes/Bacteroidetes ratio) were chosen as the primary endpoint. Other assessed indicators include:

• Tracking of time to clinical improvement by two points on a seven-point ordinal scale for clinical improvement according to R&D Blueprint: COVID-19 Therapeutic Trial Synopsis (WHO, 2020) or time to hospital discharge (whichever comes first)
• Monitoring the length of oxygen dependence
• Monitoring of laboratory markers of inflammation - serum peripheral blood CRP levels
• Monitoring of mortality

Inclusion Criteria:

• The subject is willing and able to provide informed consent prior to any study procedure.
• Age at the time of screening between 18 and 85 years inclusive.
• Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) or immunochromatographic detection of SARS CoV-2 specific antigens no more than three days prior to randomization.
• COVID-19 symptoms lasting less than or equal to seven days, including.
• Subject is currently hospitalized and requires medical care due to COVID-19 disease and was admitted at most two days prior to randomization.
• Peripheral blood oxygen saturation <94% on air (as measured by pulse oximetry or arterial blood sampling) at the time of inclusion in the trial.

Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment for COVID-19 disease.
• Concomitant treatment of COVID-19 with other non-standard-of-care medications less than 24 hours prior to initiation of the study intervention dosing (excluding remdesivir, corticosteroids, casirivimab, imdevimab, or bamlanivimab).
• Immunosuppressant treatment three months prior to hospital admission (excluding topical and inhaled corticosteroids or systemically administered corticosteroids at a dose equivalent to <40 mg Prednisone)
• Necessity of invasive pulmonary ventilation.
• Patients with known primary or secondary immunodeficiency.
• History of Crohn's disease or ulcerative colitis.
• Abnormal screening laboratory results - laboratory abnormalities that, in the opinion of the investigator, will interfere with completion of participation in the clinical trial or will interfere with the results of the trial.
• Participation in another clinical trial of a drug or medical device, or less than 30 days have elapsed since the completion of participation in another trial or use of the investigational drug or device.
• Other probiotic supplementation.
• Hypersensitivity to any ingredient of a product administered during a clinical trial.
• Women who are pregnant or breastfeeding.
• Patients with preterminal and terminal organ failure (COPD GOLD 3 and 4, CKD G4 and G5, NYHA 3 and 4).
• Any condition that, in the opinion of the investigator, may compromise the patient's ability to provide informed consent and/or comply with all required study procedures.