The COVID-19 pandemic has infected over 26 million and killed at least 450,000 Americans as of 4 February
2021. Early reports show coinfections are possibly the greatest predictor of disease severity. Mixed viral/bacterial
pneumonias are notoriously difficult to treat. The most extensively researched respiratory coinfection is influenza
and Streptococcus pneumoniae, which contribute significant morbidity and mortality during normal respiratory
infection seasons. Despite nearly two decades of vaccination with the highly effective pneumococcal conjugate
vaccine (PCV), S. pneumoniae (Spn or the pneumococcus) remains a significant cause of community acquired
pneumonia, sepsis, and meningitis. Much pneumococcal morbidity and mortality occurs during seasonal and
pandemic flus. The physiological reasons for this are incompletely understood despite extensive investigation
into this critical aspect of pneumococcal pathogenesis. Anti-viral immunological shifts, “activation” signals,
proinflammatory upregulation of adhesins, and sialic acid availability have all been implicated. The general host
responses observed during flu (fever, strong inflammatory cytokine profile, and release of DAMPS) are
recapitulated during COVID-19. Spn is a normal colonizer of the human nasopharynx and a febrile state has
been shown to lead to invasive pneumococcal disease by “activating” pneumococci. This also occurs with
respiratory viruses other than flu and is likely to occur during COVID-19-associated fever, promoting the
development of secondary bacterial pneumonia. A recent single-site study found S. pneumoniae to be the most
common coinfection in SARS-CoV-2 infected individuals and a significant source of mortality in the aged.
Although much work has been conducted with influenza/Spn coinfections, essentially nothing is known about
SARS-CoV-2/Spn coinfections. As the world braces for multiple waves of SARS-CoV-2, it is of paramount
importance to understand how these pathogens interact to promote severe disease.
The long-term goal of this research program is to understand the interaction between SARS-CoV-2 and the
pneumococcus; the objective here is to investigate the mechanisms of SARS-CoV-2 + pneumococcal disease
pathogenesis during mixed infections and to model disease in appropriate animal models. The overarching
hypothesis is that the host response to SARS-CoV-2 promotes invasive pneumococcal disease (IPD),
ultimately resulting in increased disease severity including mixed pneumonia. More specifically, we
hypothesize the inflammatory milieu created by SARS-CoV-2 infection upregulates pIGr, PafR, LamininR, and
K-10, adhesins utilized by Spn to facilitate IPD. We further hypothesize that common COVID-19 treatments
could impact the severity of coinfection.