RFA-IP-22-004, Component A _ Credible Effectiveness Measures of Seasonal Influenza, COVID-19 and Other Respiratory Virus Vaccines against Ambulatory Care for Acute Illness in Texas (and Component D).

COMPONENT A - PROJECT SUMMARY/ABSTRACT: Influenza (Flu) viruses are constantly evolving, requiring vaccines to be reformulated every season. New SARS- CoV-2 (SC2) variants have caused recurrent Coronavirus Infectious Disease - 2019 (COVID) surges in different regions of the United States through the winter of 2021-22. Estimating ongoing real-world Flu and COVID vaccine effectiveness (VE) against ambulatory care for acute illness (ACAI) are essential in evaluating the protection provided by nationwide vaccination programs and for monitoring the duration of protection afforded by respective vaccines each of which are high priorities for fulfilling the CDC's mission of serving as the nation's health protection agency. Our long-term research goal is to advance the understanding of the epidemiology and prevention of respiratory virus (RV) infections (i.e., seasonal and pandemic influenza, SC2 and Other Respiratory Viruses (ORVs) such as Respiratory Syncytial Virus [RSV]) while reducing the burden of disease and improving the health of the population. We plan to systematically evaluate the VE against ACAI associated with lab-confirmed influenza, COVID and vaccine-preventable ORVs with respective CDC recommended vaccinations in the Baylor Scott & White Health, Central Texas (BSWCTX) enrollment eligible population. The objective is to obtain reliable vaccination information and to provide accurate interim and annual estimates of VE to prevent ACAI in respective RV vaccine age-eligible population. Our central hypothesis is that timely and accurate measurement of VE and burden of illness due to vaccine preventable RVs is sustainable. The rationale is that by assessing the interim and annual VE against vaccine preventable RVs, the CDC ACIP can modify recommendations for receiving the vaccines and booster doses as well as use of appropriate antiviral agents. The specific aims are to: 1) Measure effectiveness of seasonal and pandemic Flu, COVID and vaccine-preventable ORV vaccines against ACAI for respective lab-confirmed mild to moderate infection in at least 1,000 children and adults from the 2022-23 to 2026-27 seasons. 2) Monitor ongoing Flu and SC2 viral evolution by genomic sequencing among at least 1,000 enrolled children and adults from the 2022-23 to 2026-27 seasons. 3) Perform potentially year-round SC2 surveillance during periods when Flu viruses are not circulating to measure current COVID VE against ACAI for lab-confirmed mild to moderate SC2 infection in children and adults from the 2022-23 to 2026-27 seasons. To accomplish these aims, we will estimate real-time VE in the ambulatory setting using a test-negative design, estimate burden of illness of vaccine preventable RVs in the BSWCTX burden subset, and examine factors affecting VE. The proposed research is innovative as we have adapted methods to include verified vaccinations and accurate lab diagnosis of RV infections with one or both influenza and SC2 in participants who are systematically screened for eligibility and enrolled using a well-defined ACAI case-definition in our approach, enabling us to aptly measure VE and burden of illness of influenza, COVID, and ORVs in the West South Central United States.