Gene

2019-20 coronavirus outbreak

Biology

Tissue tropism

Virology

Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Coronavirus disease 2019 (COVID-19)

Immunology

Genetics

Immune system

Vaccination

Tropism

Infectious disease (medical specialty)

Internal medicine

Coronavirus Infections

Medicine

Virus

Pandemic

Innate immune system

Influenza A virus

Heterologous

Disease

Cell Reports

Since the vast majority of species solely rely on innate immunity for host defense, it stands to reason that a critical evolutionary trait like immunological memory evolved in this primitive branch of our immune system. There is ample evidence that vaccines such as bacillus Calmette-Guérin (BCG) induce protective innate immune memory responses (trained immunity) against heterologous pathogens. Here we show that while BCG vaccination significantly reduces morbidity and mortality against influenza A virus (IAV), it fails to provide protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In contrast to IAV, SARS-CoV-2 infection leads to unique pulmonary vasculature damage facilitating viral dissemination to other organs, including the bone marrow (BM), a central site for BCG-mediated trained immunity. Finally, monocytes from BCG-vaccinated individuals mount an efficient cytokine response to IAV infection, while this response is minimal following SARS-CoV-2. Collectively, our data suggest that the protective capacity of BCG vaccination is contingent on viral pathogenesis and tissue tropism.

BCG vaccination provides protection against IAV but not SARS-CoV-2