INTRANASAL APPLICATION OF LACTOCOCCUS LACTIS W 136 BACTERIA EARLY IN SARS-Cov-2 INFECTION MAY HAVE A BENEFICIAL IMMUNOMODULATORY EFFECT: A PROOF-OF-CONCEPT STUDY
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Abstract
Justification
Stimulation of early innate anti-viral responses during the early phase of SARS-COV-2 infection oxygen may improve evolution of illness and late pulmonary complications. This may be possible using a TLR agonist such as a probiotic bacterium possessing desirable immunomodulatory properties.
Method
We performed a non-contact, open-label, prospective randomized clinical trial comparing intranasally applied Lactococcus lactis W136 with saline irrigation alone in patients within 96 hours of diagnosis of SARS-COV-2 infection not requiring supplemental oxygen.
Results
Twenty-three of a planned forty participants aged 18-59 without comorbidities were recruited. Irrigation with intranasal L lactis W136 twice-daily for fourteen days of was associated with a nasal response characterised by increase in the symptom of Facial and Throat pain/discomfort, and with a lesser severity in symptoms of i) Fatigue ii) Olfactory dysfunction and iii) Breathlessness. Safety and tolerability were good, with no acute infections or severe deteriorations.
Interpretation
Facial and throat pain may correspond to postulated mechanism of action corresponding to activation of innate defences with antiviral effects and may explain the potentially protective effects seen. Intranasal L lactis W136 irrigations may thus represent a potentially inexpensive, safe, and easily scalable non-antigen based therapeutic for the continuing global SARS-COV-2 pandemic.
Data availability statement
Data is available on request from the senior author, Dr Desrosiers: martin-yvon . desrosiers . med@ssss . gouv . qc . ca
Funding
This work was supported with internal funds from the Desrosiers laboratory at the Centre de Recherche du Centre Hospitaller de l’Université de Montreal (CRCHUM).
Competing Interests
Dr Desrosiers holds equity in Probionase Therapies inc., Which commercialises Lactococcus lactis W136 for chronic rhinosinusitis.
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SciScore for 10.1101/2021.04.18.21255699: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Approval was obtained from Health Canada (Health Canada registration number: 249512) and the CHUM Institutional Review Board and Ethics committee (Registration No. 20.012) prior to trial performance.
Consent: Informed consent was obtained from all participants prior to inclusion in the study.Sex as a biological variable Healthy males and females aged 18-59 years without comorbidities were recruited. Randomization Study Design: We performed a non-contact, open-label, prospective randomised clinical trial comparing intranasally applied Lactococcus lactis W136 with saline irrigation alone in patients within 96 hours of diagnosis of SARS-COV-2 infection. Blinding Strategies for reducing bias: … SciScore for 10.1101/2021.04.18.21255699: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Approval was obtained from Health Canada (Health Canada registration number: 249512) and the CHUM Institutional Review Board and Ethics committee (Registration No. 20.012) prior to trial performance.
Consent: Informed consent was obtained from all participants prior to inclusion in the study.Sex as a biological variable Healthy males and females aged 18-59 years without comorbidities were recruited. Randomization Study Design: We performed a non-contact, open-label, prospective randomised clinical trial comparing intranasally applied Lactococcus lactis W136 with saline irrigation alone in patients within 96 hours of diagnosis of SARS-COV-2 infection. Blinding Strategies for reducing bias: This trial was single blinded and open label. Power Analysis not detected. Cell Line Authentication Authentication: Given the lack of validated instruments to measure SARS-COV-2 symptoms, we opted to assess all of the symptoms accepted as reported in SARS-COV-2 infection at the time of trial design. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, in this instance, systemic involvement does not appear to be present, as at same timepoints where dyspnea is reported as maximal, the same individual reported a score of “0” for every other measured symptom, having completely recovered their sense of smell and manifesting no Fatigue, Limitation of activities or chills. On telephone follow up one month after end of study, this subjects’ symptoms had cleared completely. This may be considered to be reflection of the discrepancies involved between subjective questionnaires and objective assessments in other studies of SARS-COV-2 and serve to highlight the need to perform future studies in-person, with nasal examinations to collect secretions and assess toxicity, and use of home pulse oximetry to accurately assess O2 saturation. A concern may be the effectiveness in the context of emerging variants increasing contagion and potentially reducing vaccine efficiency. variants. Our postulated mechanism of action suggests induction of non-specific anti-viral responses which should not be modified by the modification of antigen targets on the virus, as can be observed with variants, but will need to be confirmed by monitoring subject’s variant status in future studies. LIMITATIONS: This study has major limitations. This proof-of-concept study was designed to assess a novel therapy in the context of the early pandemic and was powered to detect only major effects, if present. While our estimates of ability to perform irrigation a...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04458519 Recruiting Efficacy of Intranasal Probiotic Treatment to Reduce Severit… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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