Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge.
Hilligan, Kerry L. 1, 2, *; Namasivayam, Sivaranjani 1, *; Clancy, Chad S. 3; O'Mard, Danielle 1; Oland, Sandra D. 1; Robertson, Shelly J. 4; Baker, Paul J. 5; Castro, Ehydel 5; Garza, Nicole L. 6; Lafont, Bernard A.P. 6; Johnson, Reed 6; Ronchese, Franca 2; Mayer-Barber, Katrin D. 5; Best, Sonja M. 4; Sher, Alan 1
[Report] Journal of Experimental Medicine. 219(2):e20211862, February 7, 2022.

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: In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guerin (BCG) has been reported to confer nonspecific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 (SCV2) and results in reduced viral loads in non-transgenic animals infected with an [alpha] variant. The observed increase in host resistance was associated with reductions in SCV2-induced tissue pathology, inflammatory cell recruitment, and cytokine production that multivariate analysis revealed as only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and ensuing immunopathology. While intravenous BCG vaccination is not a clinically acceptable practice, our findings provide an experimental model for identifying mechanisms by which nonspecific stimulation of the pulmonary immune response promotes host resistance to SCV2 lethality.

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