BACKGROUND: National data previously demonstrated an increase in invasive disease due to non-type b Haemophilus influenzae from the 2000s to the 2010s. Significant shifts in the epidemiology of respiratory pathogens in children have occurred in the post-SARS-CoV-2 era. We examined pediatric invasive H. influenzae disease in the pre- and post-SARS-CoV-2 years. METHODS: Invasive H. influenzae infections were identified from culture records of the Texas Children's Hospital microbiology laboratory from January 2011 to December 2023. Invasive cases were considered those with isolation of H. influenzae from a sterile site. The annual number of cases/1000 admissions was used as a surrogate for incidence. RESULTS: One hundred twenty-four cases of invasive disease were identified. The median age was 1.9 years, and 57% had pre-existing comorbidities. The most common diagnosis was bacteremia without a focus (50%), followed by pneumonia (27%). An increase in invasive disease occurred from 2011 to 2019 (P <
0.002) followed by a decline from 2020 to 2021 (P = 0.04) and a subsequent resurgence (P <
0.002). Bacteremia declined in 2020 followed by an increase in 2022 (P = 0.003)
50% of pneumonia cases occurred in the final 2 study years. The most common strain types were nontypeable H. influenzae (NTHi, 52.4%), type a (17.5%) and type f (15.9%). NTHi declined in 2020 followed by a peak in 2022, exceeding prepandemic rates (P = 0.002). Respiratory viruses were codetected in 52.9% of those tested. CONCLUSIONS: The frequency of pediatric invasive H. influenzae has undergone change throughout the SARS-CoV-2 pandemic. Recent increases in disease activity are driven by NTHi presenting as bacteremia and pneumonia. Given the high burden of disease, these trends should continue to be monitored.