Efficacy of Intranasal Probiotic Treatment to Reduce Severity of Symptoms in COVID19 Infection
Condition: COVID-19 Infection
MeSH terms: Infections; Communicable Diseases; COVID-19
Study type: Interventional

Summary: 
      Randomised, single-blinded trial. Patients with a diagnosis of COVID-19 infection within the
      past 96 hours and not requiring hospitalization will be recruited into a trial of BID Nasal
      irrigation for 14 days, followed by a 14 day observation period. Irrigation will be performed
      with either Probiorinse probiotic nasal irrigation solution or NeilMed Sinus rinse. Patients
      will be able to identify their treatments, but study staff will be blinded as to assignment.
    

Detailed description: 
      BACKGROUND/OBJECTIVE

      The potential role of the microbiome in COVID-19 disease remains little explored, yert may
      offer an unique therapeutic opportunity for its treatment. Airway inflammation and microbiome
      dysbiosis is present in COVID-19 patients and is related to evolution. The limited
      information on airway inflammation in COVID-19 suggests greater inflammation, as assessed by
      serum markers of inflammation, is associated by more severe disease. Late cell-mediated
      T-cell activation is paradoxically accompanied by TLR expression downregulation, which
      contributes to dysfunctional immune regulation. Individual predisposition to heightened
      inflammatory responses may contribute to this.

      The investigators believe this early TLR downregulation is an important feature of the
      disease, allowing the disease to reproduce unchecked and spread during a prolonged
      asymptomatic shedding period.

      Immune-evasion strategies are common to several viral infections such as influenza,
      respiratory syncytial virus, and human rhinovirus, COVID-19 may exploit this as well.

      Lung microbiome data in COVID-19 is limited, but a small dataset of 8 hospitalised cases has
      been reported from China suggests pulmonary inflammation can be influenced by the microbiome
      at the time of intubation, arguing the need for a more favorable upper airway microbiome.

      Based on the above information, the investigators believe that administration of probiotic
      bacteria directly to the upper airway via irrigation to patients receiving a diagnosis of
      COVID-19 will improve the status of the upper airway microbiome and reduce symptom severity
      and disease in patients with COVID-19 disease not requiring ICU admission or intubation.

      The investigators believe intranasally applied 'health-inducing' bacteria will favorably
      modulate the response to COVID-19 infection, reducing its severity and complications.
      Probiorinse may exert potentially beneficial effects in COVID-19 infection via two potential
      and distinct mechanisms:

        1. Activation of the innate immune system via enhanced TLR signalling:

           - Abundant TLR ligands present on the probiotic bacterial capsule may counter the
           downregulation in TLR expression and function seen with COVID-19 infection.

        2. Promotion of a 'healthy' microbiome profile in the nasopharynx:

             -  Reducing "seeding" the lower respiratory tract with inappropriate bacteria or
                pathogens.

             -  Conditioning inappropriate or excessive immune responses of the airway

      The purpose of this clinical trial is thus to compare the safety and validity of intranasal
      irrigation with Lactococcus lactis W136 with saline nasal irrigation alone in patients with
      mild COVID-19 infection.

      METHODOLOGY

      Consent process in the current context of the COVID-19 pandemic: Verbal consent and
      confirmation of consent in writing or electronically.

      Participants will be recruited via posted signs in the COVID-19 clinic and hospital Intranet
      advertising a research project for individuals diagnosed with COVID-19 infection.

      This study will include three (3) periods, which will take the form of telephone calls /
      email contacts:

        1. Eligibility determination period (Day 0)

        2. Treatment period (Day 1 to Day 14): Probiorinse or Saline solution

        3. Follow-up period (Day 21 and Day 28)

      STATISTICAL ANALYSIS

      Analysis population:

      The primary analysis population for the efficacy endpoints will be the randomized ITT
      population which includes all patients who have been allocated to a randomized treatment
      regardless of whether the treatment kit was used or not. The efficacy analyses will be
      conducted according to the treatment to which they were randomized.

      The analysis population for safety endpoints is defined as all patients exposed to study
      medication, regardless of the amount of treatment administered. The safety analyses will be
      conducted according to the treatment patients actually received. The treatment emergent
      period is defined as the time from the first administration of study medication to Day 14 of
      post treatment period.

      Data Analysis:

      The following null hypothesis and alternative will be tested for the Probiorinse arm against
      NeilMed Sinus Rinse:

        -  H0: No treatment difference between Probiorinse and NeilMed Sinus Rinse.

        -  H1: There is a treatment difference between Probiorinse and NeilMed Sinus Rinse

      Descriptive statistics including number of subjects mean, standard error, and least squares
      (LS) means will be provided. In addition, difference in LS means and the corresponding 95%
      confidence intervals (CI) will be provided along with the p-values.
    

Intervention name(s): Probiorinse; Saline solution
Intervention type(s): Other; Other
Intervention description(s): Nasal irrigations with probiotic twice-daily for a period of fourteen days; Nasal irrigations with saline-only twice-daily for a period of fourteen days
Other intervention name(s): Natural health products; Probiotic; Natural health product
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single-blinded, randomized, prospective trial
Masking: Double (Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: COVID-19; Nasal irrigation; Probiotic; Microbiome; Lactococcus lactis W136