Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85

The Covid-19 pandemic has been characterised by acute respiratory distress syndrome (ARDS)
accompanied by a systemic cytokine-storm resulting in severe illness, respiratory failure and
death in some. Severe Acute Respiratory Syndrome (SARS)- Coronavirus (Cov-2) (COV) infection
per se is not the only underlying issue here, as it is becoming evident that ARDS is
relatively rare amongst infected subjects, and appears to be associated with gross
dysregulation of ensuing host-anti-viral responses resulting in collateral
immune-inflammatory-mediated damage to host tissues. Rather than waiting for susceptible
subjects to present with COV-associated ARDS, the investigators propose treatment of healthy
health care workers (HCW) with a therapeutic agent which simultaneously targets front-line
innate anti-viral immune defences, together with the core mechanism that controls immune
response intensity in the airways. This research addresses the hypothesis that resistance to
development of severe COV-associated respiratory disease in front-line HCW, even in those who
develop a primary infection, can be boosted via a regimen of daily dosing with the
bacterial-derived immunomodulatory agent OM85.

Aims

1. To demonstrate that daily treatment with OM85 will prevent HCW developing acute
respiratory infections (ARI) necessitating removal from the workforce.

2. To elucidate the mechanism of action by which OM85 regulates host immune responses
against COV.

Mechanistic studies will primarily test the hypothesis that OM85 pre-treatment modulates the
systemic immunoinflammatory response to COV, selectively attenuating potentially pathogenic
pro-inflammatory pathways without compromising activation of innate immune pathways central
to pathogen clearance. The investigators will additionally collect samples to test the
secondary hypothesis that the host response to COV displays uniquely aggressive
pro-inflammatory features that differ from those observed with non-COV respiratory
infections.

Experimental design: participants will be randomised into two groups; Immediate treatment
with OM85 (n=500) or wait-list control with OM85 commencing three months later (n=500).
Venous blood samples will be collected from each subject at four time points. Sera will be
stored from each time point for assay of COV-specific antibody. For the mechanistic studies
the investigators will focus on two groups of subjects who test respectively positive or
negative to COV during a defined respiratory illness. These will be further stratified by
treatment (OM85 treated (OM+) versus non-treated (OM-) prior to ARI, yielding 4 sets (each
n=50) of test samples collected at acute infection which will be utilized for two discrete
cross-comparisons: (i) COV+/OM+ versus COV+/OM-, and (ii) COV-/OM+ versus COV-/OM-. Analyses
in (i) will be prioritised as they relate exclusively to host-responses to COV and effects of
treatment thereon; those in (ii) which will contrast COV-associated response with those
elicited by conventional respiratory pathogens and compare respective susceptibility to OM85.