Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells

Alok K. Singh, Rulin Wang, Kara A. Lombardo, Monali Praharaj, C. Korin Bullen, Peter Um, Manish Gupta, Geetha Srikrishna, Stephanie Davis, Oliver Komm, Peter B. Illei, Alvaro A. Ordonez, Melissa Bahr, Joy Huang, Anuj Gupta, Kevin J. Psoter, Patrick S. Creisher, Maggie Li, Andrew Pekosz, Sabra L. KleinSanjay K. Jain, Trinity J. Bivalacqua, Srinivasan Yegnasubramanian, William R. Bishai

Research output: Contribution to journalArticlepeer-review


Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

Original languageEnglish (US)
Article number107733
Issue number10
StatePublished - Oct 20 2023


  • Immune response
  • Model organism
  • Virology

ASJC Scopus subject areas

  • General


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