Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge

• Published in: The Journal of experimental medicine Vol. 219; no. 2
• Main Authors: Hilligan, Kerry L, Namasivayam, Sivaranjani, Clancy, Chad S, O'Mard, Danielle, Oland, Sandra D, Robertson, Shelly J, Baker, Paul J, Castro, Ehydel, Garza, Nicole L, Lafont, Bernard A P, Johnson, Reed, Ronchese, Franca, Mayer-Barber, Katrin D, Best, Sonja M, Sher, Alan
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.02.2022
• Subjects: Administration, Intravenous; Angiotensin-Converting Enzyme 2 - metabolism; Animals; BCG Vaccine - immunology; Brief Definitive Report; Chemokines - metabolism; Covid-19; COVID-19 - immunology; Humans; Infectious Disease and Host Defense; Inflammation - pathology; Innate Immunity and Inflammation; Mice; Mice, Inbred C57BL; Mice, Transgenic; SARS-CoV-2 - immunology; Viral Load
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20211862

In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (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 α 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.