Dynamic single-cell RNA sequencing reveals that intravenous BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation
COVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guérin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 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 together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits 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, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing 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. Overall design: Groups of hamsters were intravenously (I.V.) administered saline or were vaccinated (I.V.) with 5×10^6CFU of BCG-Tice. 30 days after vaccination animals were challenged with 5×10^5TCID50units of SARS-CoV-2 (SCV2) (Wuhan-1/2020) by the intranasal route. At D4 and D7 post-challenge animals were sacrificed for analysis. 3 animals (BCG only) were not infected with SCV2 and were sacrificed 30 days post-vaccination to serve as controls