IMPORTANCE: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden. OBJECTIVE: To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022. DESIGN, SETTING, AND PARTICIPANTS: Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.9 million persons across 10 US states. A case was defined as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis or streptococcal toxic shock syndrome between January 1, 2013, and December 31, 2022. Demographic and clinical data were collected from medical record review. From 2013 to 2014, available isolates were emm typed and antimicrobial susceptibilities determined using conventional methods; from 2015 onward, whole-genome sequencing was used. MAIN OUTCOMES AND MEASURES: Incidence rates by sex, age, race, and selected risk factors; clinical syndromes, outcomes, and underlying patient conditions; and isolate characteristics, including antimicrobial susceptibility. RESULTS: Surveillance in 10 US states identified 21 312 cases of invasive GAS from 2013 through 2022, including 1981 deaths. The majority of cases (57.5%) were in males. Among case-patients, 1272 (6.0%) were aged 0 to 17 years, 13 565 (63.7%) were aged 18 to 64 years, and 6474 (30.4%) were 65 years or older; 5.5% were American Indian or Alaska Native, 14.3% were Black, and 67.1% were White. Incidence rose from 3.6 per 100 000 persons in 2013 to 8.2 per 100 000 persons in 2022 (P < .001 for trend). Incidence was highest among persons 65 years or older; however, the relative increase over time was greatest among adults aged 18 to 64 years (3.2 to 8.7 per 100 000 persons). Incidence was higher among American Indian or Alaska Native persons than in other racial and ethnic groups. People experiencing homelessness, people who inject drugs, and residents of long-term care facilities had substantially elevated GAS incidence rates. Among tested isolates, those nonsusceptible to macrolides and clindamycin increased from 12.7% in 2013 to 33.1% in 2022. CONCLUSIONS: Invasive GAS infections increased substantially in 10 US states during a surveillance period from 2013 to 2022. Accelerated efforts to prevent and control GAS are needed, especially among groups at highest risk of infection.

Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I(2). FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I(2)=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I(2)=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I(2)=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I(2)=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I(2)=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I(2)=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I(2)=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I(2)=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I(2)=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I(2)=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I(2)=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.