Streptococcus pneumoniae is a major causative agent of both noninvasive and invasive infections in both adults and children and is the leading cause of bacterial pneumonia and pneumonia-related death in children less than five years old worldwide. The introduction of the pneumococcal conjugate vaccine (PCV), which contains capsule components of the most prevalent and invasive serotypes, has dramatically decreased invasive pneumococcal disease (IPD) and death worldwide. In the U.S., there are clear racial and ethnic disparities in IPD. A recent study prior to global coronavirus pandemic (COVID-19) demonstrated that older blacks (>65 years) were 12% more likely to suffer from high-risk pneumococcal conditions compared to non-blacks. In the period after the COVID-19 pandemic, this disparity likely is wider given the challenges to access primary health care, and decreased rates of uptake of routine vaccinations, including those against S. pneumoniae. Recently, we have observed several healthy children (>5 years of age) who have received the routine recommended doses of PCV13 then go on to develop invasive disease in the form of necrotizing pneumonia, bacteremia, meningitis, and brain abscess.We hypothesize that Invasive pneumococcal disease (IPD) among children verified to have received PCV13 are from serogroups contained within PCV13 and reflect immune escape mechanisms and not vaccine failure. Secondary hypothesis:

(i) Serotypes 3, 19A and 19F infections predominate among breakthrough infections, demonstrating less real world effectiveness of PCV13 in otherwise, healthy, immune competent children.

(ii) The breakthrough infections could represent a novel serotype which needs to be interrogated at the molecular level for eventual inclusion into current vaccination strategies.

This is an observational epidemiology secondary analyses of patients who meet inclusion criteria for IPD.

SA1. Determine risk factors and compare differences among risks for patients identified to have invasive pneumococcal infections during three periods: 1.Pre-COVID-19 Pandemic, 2017-2019; 2.During COVID-19 Pandemic, 2020-2022; 3.Post-COVID-19 Pandemic, 2023- 2025

SA2. Characterize the molecular epidemiology of clinical isolates from children who presented for invasive pneumococcal infections from University of Chicago's hospitals and affiliate institutions (e.g., partners through the Institute of Translational Medicine) and have evidence of complete vaccination against Streptococcus pneumoniae using PCV10, or PCV13 vaccines.

Aim 1 employs retrospective data analyses using surveillance tool, and also applies statistical analyses and geospatial analyses.

Aim 2 employs an observational epidemiology study design, and then applies standard clinical research methods to collect bio specimens from hospitalized patients. We will partner with partners of the Institute of Translational Medicine to perform the molecular analyses in characterizing the bacterial isolates collected, including serotyping and identifying specific virulent factors.

1. SAS or R

2. ArcGIS

3. Molecular genomic analyses

ID Week -national conference for infectious diseases

APA- national public health meeting (annual)

PAS-national pediatric academic societies meeting (annual)