text: The OM 85 bacterial lysate inhibits SARS CoV 2 infection of epithelial cells by downregulating SARS CoV 2 receptor expression Treatments for coronavirus disease of 2019 COVID 19 which is caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 are urgently needed but remain limited SARS CoV 2 infects cells through interactions of its spike S protein with ACE2 and TMPRSS2 on host cells Multiple cells and organs are targeted particularly airway epithelial cells OM 85 a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile is widely used to prevent recurrent respiratory infections We found that airway OM 85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung suggesting that OM 85 might hinder SARS CoV 2 host cell interactions To investigate whether and how OM 85 treatment protects non human primate and human epithelial cells against SARS CoV 2 ACE2 and TMPRSS2 mRNA and protein expression cell binding of SARS CoV 2 S1 protein cell entry of SARS CoV 2 S protein pseudotyped lentiviral particles and SARS CoV 2 cell infection were measured in kidney lung and intestinal epithelial cell lines primary human bronchial epithelial cells and ACE2 transfected HEK293T cells treated with OM 85 in vitro OM 85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells OM 85 also strongly inhibited SARS CoV 2 S1 protein binding to SARS CoV 2 S protein pseudotyped lentivirus entry into and SARS CoV 2 infection of epithelial cells These effects of OM 85 appeared to depend on SARS CoV 2 receptor downregulation OM 85 inhibits SARS CoV 2 epithelial cell infection in vitro by downregulating SARS CoV 2 receptor expression Further studies are warranted to assess whether OM 85 may prevent and or reduce the severity of COVID 19 