Centers for Disease Control and Prevention

Infectious susceptibility is a component of many inborn errors of immunity. Nevertheless, antibiotic use is often used as a surrogate in history taking for infectious susceptibility, thereby disadvantaging patients who present with viral infections as their phenotype. Further complicating clinical evaluations are unusual manifestations of viral infections which may be less familiar that the typical respiratory viral infections. This review covers several unusual viral phenotypes arising in patients with inborn errors of immunity and other settings of immune compromise. In some cases, chronic infections lead to oncogenesis or tumor‐like growths and the conditions and mechanisms of viral‐induced oncogenesis will be described. This review covers enterovirus, rubella, measles, papillomavirus, and parvovirus B19. It does not cover EBV and hemophagocytic lymphohistiocytosis nor lymphomagenesis related to EBV. EBV susceptibility has been recently reviewed. Our goal is to increase awareness of the unusual manifestations of viral infections in patients with IEI and to describe treatment modalities utilized in this setting. Coincidentally, each of the discussed viral infections can have a cutaneous component and figures will serve as a reminder of the physical features of these viruses. Given the high morbidity and mortality, early recognition can only improve outcomes.

Background While the number of immunocompromised (IC) individuals continues to rise, the existing literature on influenza vaccine effectiveness (VE) in IC populations is limited. IC individuals have a higher risk of severe influenza and influenza-related hospitalizations, and understanding the VE of the seasonal influenza vaccines in IC populations remains paramount. Methods Using 2017-2018 US Flu VE Network (US Flu VE) data, we examined the VE of the 2017-2018 seasonal influenza vaccine against symptomatic influenza in outpatient settings among IC adults. Patients were enrolled from outpatient sites in five states. IC status was determined by ICD-10 codes. We used logistic regression and adjusted for enrollment site, race, self-reported general health status, age, and onset date of symptoms. Separate models were used to calculate and compare the VE for non-IC and IC among outpatient adults >18 years. Results 5671 participants were included in the adult analytic dataset, and 455 (8%) were IC. The VE among non-IC was 31% (95% CI: 22, 39) and among IC participants was -4 % (95% CI: -66, 35). P-value for interaction by IC status was 0.100. Conclusion We observed lower VE against symptomatic influenza among non-hospitalized patients with immunocompromising conditions though the difference was not statistically significant. This study demonstrates the capacity to study a large IC population using an existing influenza VE network and contributes to the literature to support large, multicenter VE studies for IC populations. Disclosures Richard K. Zimmerman, MA; MD; MPH; MS, Sanofi Pasteur: Grant/Research Support MaryPatricia Nowalk, PhD, RDN, Merck & Co.: Grant/Research Support|Merck & Co.: Honoraria|Sanofi: Grant/Research Support Fernanda P. Silveira, MD, Ansun: Grant/Research Support|Eurofins Viracor: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Grant/Research Support|Regeneron: Grant/Research Support|Takeda: Advisor/Consultant Emily T. Martin, PhD, MPH, Merck: Grant/Research Support

Background A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but there are limited data on long-term immunogenicity. We assessed persistence of measles and rubella neutralizing antibodies among adults after receipt of three MMR doses. Methods Adults who received two MMR doses in childhood and a third dose as young adults (aged 18-28 years) in 2009-2010 were recalled at around 5 (2014-2016) and 9-11 (2019-2021) years after receipt of the third MMR dose. Measles and rubella antibody levels were assessed by plaque-reduction and soluble immunocolorimetric neutralization assays, respectively. Participants with measles antibody concentrations < 120 mIU/ml or rubella antibody concentrations < 10 U/mL were considered potentially susceptible to infection. Generalized estimating equations models were used to estimate geometric mean concentrations (GMC) and 95% confidence intervals (CI) of antibody levels over time. Results Approximately 5 and 9-11 years after receipt of the third MMR dose, 408 (aged 22-33 years) and 304 (aged 26-37 years) adults were reassessed, respectively. For measles, GMC was 428 mIU/mL (95% CI, 392 – 468 mIU/mL) at 5 years after the third MMR dose, declining to 381 mIU/mL (95% CI, 339 – 428 mIU/mL) at 11 years after the third MMR dose (Fig 1). Measles antibody concentrations during both long-term follow-up periods declined to levels lower than before receipt of the third dose (Fig 2). At the last follow-up visit (2019-2021), 10% of participants were potentially susceptible to measles infection compared to 3% before receipt of the third MMR dose up to 11 years earlier. For rubella, GMCs were stable throughout the long-term follow-up period (63 U/mL to 65 U/mL) (Fig 3). Rubella antibody concentrations during the long-term follow-up periods remained higher than levels before receipt of the third MMR dose and were similar to levels at 1 year after receipt of the third MMR dose (Fig 2). None of the participants were susceptible to rubella at the last follow-up visit. The solid black line shows the trend in population GMC estimates from before vaccination (0 year) through 12 years after receipt of the third MMR dose. The gray lines show the measles virus antibody concentrations over time for each individual. The dotted horizontal line shows concentration <120 mIU/mL used as the cutoff for susceptibility. The vertical dotted lines represent the cutoff for susceptibility. The geometric mean concentrations (GMCs) were estimated using generalized estimating equations model. The solid black line shows the trend in population GMC estimates from before vaccination (0 year) through 12 years after receipt of the third MMR dose. The gray lines show the rubella virus antibody concentrations over time for each individual. The dotted horizontal line shows concentration <10 U/mL used as the cutoff for susceptibility. Conclusion Neutralizing antibody levels to measles and rubella remained high and persisted through 11 years after vaccination among adults who received three MMR doses. However, some adults may become susceptible to measles infection over time despite receipt of three MMR doses. Disclosures Stephen N. Crooke, PhD, Bionano Genomics: Stocks/Bonds|Caribou Biosciences: Stocks/Bonds|Pfizer: Stocks/Bonds|Vistagen Therapeutics: Stocks/Bonds Huong McLean, PhD, MPH, Seqirus: Grant/Research Support

Background On July 18, 2022, a case of paralytic polio was reported in a person from Rockland County, New York. In August 2022, the proportion of children in Rockland County with 3 doses of polio vaccine by age two was 60.3%. That month, Rockland County, New York State, and CDC initiated a campaign to conduct physician-mediated patient outreach to improve Inactivated Polio Vaccine (IPV) coverage in Rockland County. Methods We contacted 38 Vaccines for Children enrolled providers, serving patients aged 3-60 months who were overdue for polio vaccinations, to send reminders to parents. Providers contacted parents by phone, text message, or mailed personalized letter. To assess success of the intervention on vaccine uptake, we retrospectively identified cohorts of patients missing >1 dose of polio vaccine in the New York State Immunization Information System as of August 9, for baseline years 2017 and 2018, and for intervention year 2022. We used logistic regression to compare the odds of receiving polio vaccine among under-vaccinated cohorts during August 15–October 31 of the baseline and intervention years. Results Thirty providers conducted patient outreach using phone calls (19 providers), text messages (4 providers), and letters (14 providers). At the outset, 4,887 patients aged 3-60 months were missing 1 or more recommended doses of polio vaccine. During the 10 weeks following initiation of outreach, 1,292 (26.4%) of these patients received an IPV dose; 7.1% were 3-6 months old, 17.9% 7-11 months, 27.9% 1 year, 47.1% 2-5 years. Of the IPV doses received, 1st, 2nd, and 3rd doses accounted for 7.5%, 33.1% and 59.4%, respectively. The odds of an un- or under-vaccinated patient receiving a dose of polio vaccine during the 10-week analysis period were significantly higher in 2022 compared to 2017 (OR=1.41, 95% CI [1.27-1.56]) and 2018 (OR=1.46, 95% CI [1.32-1.62]). Conclusion Following physician-mediated patient outreach urging vaccination among under-immunized children in August 2022, 26% of undervaccinated children received polio vaccine in the 10 weeks after outreach. This reflected an increased odds of vaccination by 40% compared to baseline years 2017 and 2018, highlighting the positive impact of conducting this type of outreach during a polio outbreak in an area with low vaccine coverage. Disclosures All Authors: No reported disclosures

Background Nirmatrelvir/ritonavir (N/R) protects against severe outcomes after SARS-CoV-2 (SCV2) infection, but patients and studies have described symptom and viral rebound after treatment. Our aim was to compare symptom and viral trajectories during acute illness among individuals with COVID-19 treated with N/R compared to similar individuals who did not receive any COVID-19 treatment. Methods This analysis included participants enrolled ≤ 6 days of index symptom onset in a US household transmission study who tested SCV2-positive, Mar. 2022–Mar. 2023. We followed participants for 10 days after enrollment, obtaining demographics, clinical history, daily symptoms (list of 15), medications, and specimens for SCV2 quantitative PCR. Symptomatic participants eligible for N/R were included (Fig. 1). We used propensity score matching to select untreated participants who were similar to N/R treated participants (Table 1). We assessed symptoms and viral load (when ≥ 2 nasal swab results were available) from N/R completion (N/R treated) or after seven days since symptom onset (untreated) to the end of follow up. We defined symptom rebound as an increase of ≥ 2 symptoms and viral load rebound as an increase of ≥ 0.5 log10(IU/mL) over a minimum of 5 log10(IU/mL). We used Wilcoxon Test to compare mean daily symptoms and viral loads and logistic regression to calculate odds of rebound. Case-ascertained household transmission study participants were included in this analysis if they were enrolled in March 2022 (first report of nirmatrelvir/ritonavir) or after and tested positive for SARS-CoV-2 (n=2075). We included symptomatic N/R eligible participants who had non-missing data for propensity score model variables and daily specimens and symptoms (n=1224) and then excluded N/R treated participants who did not complete N/R in 5-6 days according to EUA (n=108). Propensity score matching was performed by calculating propensity score of nirmatrelvir/ritonavir use based on age, sex, race/ethnicity, prior COVID-19, recruitment method, participant type, medical care access, COVID-19 vaccination history, comorbidities, and predominant variant at the time of index onset. The best covariate balance was achieved using nearest propensity score matching method with a ratio of 2:1 no treatment to N/R treated. Those that did not match to a treated participant were excluded (n=768). The two recruitment sources collected different specimen types (sentinel sites collected nasal swabs and remote recruitment collected saliva) and used different viral load quantification standards. Because of this, viral load analysis was limited to only those that collected nasal swabs and had at least two viral load results after nirmatrelvir/ritonavir completion or, for the no treatment participants, after day 7 since symptom onset. N/R=nirmatrelvir/ritonavir; SCV2=SARS-CoV-2; EUA=Emergency Use Agreement Results N/R treated (n=116) and untreated (n=232) participants had similar baseline characteristics (Table 1). Median days from symptom onset to N/R initiation was 2 days (IQR=1-3). Symptom rebound occurred among 32% of N/R treated and 19% of untreated participants (OR=1.95; 95% CI=1.17, 3.24; Fig. 2). Mean daily symptoms were lower among N/R treated (1.6 vs 2.0; p=0.2) and significantly lower among N/R treated when rebound did not occur (0.8 vs 1.5; p=0.01). Viral load rebound occurred among 25% of N/R treated and 13% of untreated participants (OR=2.31; 95% CI=1.17, 4.55) and mean daily viral load was significantly lower among N/R treated overall (1.5 vs 2.7), without rebound (1.1 vs 2.5), and with rebound (4.8 vs 5.6, all p < 0.05, Fig. 3). The following symptoms were elicited daily from participants: fever/feverish/chills, cough, sore throat, runny nose, nasal congestion, fatigue/feeling run down, wheezing, trouble breathing/shortness of breath, chest tightness/chest pain, loss of smell/loss of taste, headache, abdominal pain, diarrhea, vomiting, and muscle or body aches. Symptom rebound was defined as an increase of at least two symptoms after the completion of nirmatrelvir/ritonavir or, when no treatment was reported, after seven days since symptom onset. Daily symptoms after end of treatment were averaged from the day after the last day of nirmatrelvir/ritonavir or, if no treatment, day eight since symptom onset to the last available symptom diary follow up. N/R=nirmatrelvir/ritonavirFigure 3.Viral load trajectory during the first two weeks after symptom onset by nirmatrelvir/ritonavir treatment and viral load rebound visualized by (A) median viral load each day since symptom onset and proportion with viral load rebound and (B) average daily viral load after nirmatrelvir/ritonavir completion or seven days since symptom onset Nasal swabs were tested for SARS-CoV-2 by PCR using the Panther Fusion Hologic system. Viral load as logIU/mL was determined using WHO standard. Negative results were set to zero and below limit of quantification (3 logIU/mL) results were set to 1.5 logIU/mL. Viral load rebound was defined as an increase of at least 0.5 logIU/mL (with a threshold of 5 logIU/mL) after the completion of nirmatrelvir/ritonavir or, if no treatment was reported, after seven days since symptom onset. Daily viral load after end of treatment was averaged from the day after the last day of nirmatrelvir/ritonavir or, if no treatment, day eight since symptom onset to the last available viral load result. N/R=nirmatrelvir/ritonavir; IU=international units Conclusion In outpatient settings, N/R treated individuals had fewer symptoms and lower viral loads, but greater odds of symptom and viral rebound compared to similar untreated individuals. Disclosures Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edward Belongia, MD, Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support

Background Universal congenital cytomegalovirus (cCMV) screening is controversial. In 2023, we completed a study evaluating analytical and clinical sensitivity of dried blood spots (DBS) for detection of cCMV infection and disease. Analytical sensitivity is the ability of an assay to detect infection, while clinical sensitivity is an assay's ability to identify individuals with disease. The completion of this study coincided with implementation of new legislation making Minnesota the first state in the USA to mandate universal cCMV testing. Methods In six newborn nurseries in Minnesota, consented newborns were screened for cCMV, comparing PCR of saliva with PCR of the DBS obtained for routine newborn screening. Screen-positive infants had a confirmatory urine PCR, and a diagnostic clinical evaluation. Using international consensus criteria, we categorized cCMV cases as: moderate-to-severe; mildly symptomatic; asymptomatic with isolated sensorineural hearing loss (SNHL); or asymptomatic. Results From February 2016 - January 2023, among 23,644 newborns screened, 87 (3.7 per 1,000) were identified with cCMV. Analytical sensitivity of saliva was 93.1% (81); for DBS, it was 73.6% (64) by the UMN lab, and 77.0% (67) by the CDC lab. At birth, 67 (77%) infants were asymptomatic; 6 moderately-to-severely symptomatic (2 with SNHL); 10 mildly symptomatic; and 4 asymptomatic with isolated SNHL. 4 infants had delayed-onset SNHL (2 asymptomatic, 2 symptomatic). Among 20 infants with symptomatic cCMV at birth and/or SNHL, clinical sensitivity of saliva was 95% (19), and for DBS was 75% (15) in the UMN lab, and 85% (17) in the CDC lab. Conclusion This unselected screening study demonstrated a prevalence of 3.7/1000 of cCMV in Minnesota newborns. The enhancement in clinical sensitivity of DBS (over analytical sensitivity) to identify children with symptoms or sequelae suggests their usefulness for cCMV screening, though most identified infants will be asymptomatic. In parallel with this work, in the spring of 2023, Minnesota became the first state to screen all newborns for cCMV, using the newborn DBS. Continued evaluation of CMV DBS testing methods for reproducibility, efficiency, high-throughput capability and clinical correlation will be important as other states consider universal cCMV screening. Disclosures All Authors: No reported disclosures

Background On February 3, 2023, the Kazakhstan Ministry of Health was notified of 71 hospitalized cases of acute gastointestinal illness among people who had ordered food from a delivery sushi and pizza restaurant in Talgar (population=50,000). We conducted an investigation from February 4 to 16 to identify risk factors. Methods We conducted a retrospective cohort study among people who consumed food from the sushi bar from January 31 to February 1, 2023. To find additional cases, we used a line list of orders made by customers provided by the restaurant. We interviewed customers by telephone and face-to-face. Patient gastric samples and food samples were submitted for microbial testing. We conducted an environmental assessment. We performed Poisson logistic regression using R software. Results Of 381 people identified, 364 were interviewed, of which 215 (59%) had become ill. Main symptoms were abdominal pain (98%), diarrhea (94%), nausea (94%), headache (91%), chills (82%), fever (81%), and vomiting (55%). Mean illness duration was 4 days (range=1-8). Mean onset time was 34 hours (range=6-91 hours) and 33% were hospitalized. Risk of illness was significantly higher among people who ate Caesar sushi rolls (1.55, 95% confidence interval [CI]=1.18-2.04), chicken and mushroom pizza (1.74, CI: 1.16-2.5), and "American" pizza (1.59, CI: 1.21-2.09). Among people who became ill, 60% had eaten Caesar sushi rolls and 40% american pizza. Attack rate was highest among those who had chicken pizza (97%). There was no common ingedient identified in the three foods. E.coli at concentration 103 and Enterococcus spp. were detected in Caesar rolls. Of 22 gastric samples tested, B. cereus was detected in 45%, Enterococcus in 50%, E. coli in 23%. Environmental assessment found several food safety violations including improper storage conditions, prepared foods being stored with raw materials, and missing or expired workers' health and food certifications. Factors associated with acute gastrointestinal illness, Talgar, Kazakhstan, 2023 Conclusion Because multiple pathogens were detected in food and patient samples and disease was associated with multiple foods, we suspect that food contaminated at different points in the preparation process was likely the source of the outbreak. The restaurant was closed and sanitized. We made recommendations to improve food handling and safety practices. Disclosures All Authors: No reported disclosures

Background Inappropriate urine cultures (UCs) lead to misdiagnosis and unnecessary antibiotic use and can impact surveillance. The absence of pyuria on a urinalysis (UA) has a high negative predictive value for urinary tract infections (UTIs) in certain settings and can reduce unnecessary UCs. UCs performed without UA or with a negative UA indicate opportunities for diagnostic stewardship. Understanding facility variability and patient characteristics associated with inappropriate UCs can inform improvements in acute care hospitals (ACHs). Methods Using clinical microbiology data from 279 ACHs reporting UC and UA data to the PINC AI Healthcare Database, we assessed appropriateness of the first UC collected during adult hospitalizations, excluding pregnant and urologic procedure patients identified using ICD-10-CM diagnosis codes. Each UC was categorized as follows: (1) UC with at least 1 positive UA (WBC ≥10/HPF, presence of leukocyte esterase or nitrite) 24 hours before/after UC (UA+ UC), (2) UC with negative UA in 24 hours (UA- UC), and (3) UC without UA in 24 hours (no-UA UC). Overall percentages of UC categories were described by year and patient characteristics. Monthly facility-specific percentages of UCs were calculated, and facility-level variability was described by medians, quartiles 1 and 3 (Q1:Q3). Results 1.2 million incident UCs were included. Of those, 65% were UA+, 21% UA-, and 14% no-UA UCs. From 2017 to 2020, UA+ UCs increased from 60.5% to 68.2%, no-UA UCs decreased from 19.3% to 10.5%, and UA- UCs stayed at 21%. UA- and no-UA UCs were more common among male, younger age, and Medicaid patients (Figure 1). No-UA UCs were more commonly obtained on day 4 or later. The median monthly facility-level percentages of UA+, UA-, no-UA UCs were 75 (Q1:Q3, 55.6-86.5), 15 (Q1:Q3, 6.5-28.6), and 5.3 (Q1:Q3, 2.1-10.5), respectively (Figure 2). Overall Percentages of Urine Cultures Variability in Hospital Monthly Percentages of Urine Cultures (UC) in Each Category, 2017-2020, N hospital-months = 9,863 Hospital-level Variability Conclusion During the study period, urine culturing practices improved; however, 35% of incident UCs had no UA or negative UA. The high proportion of these UCs and facility-level variability of the monthly proportions call for diagnostic stewardship to identify and address causes of the potentially suboptimal UC practices. This will support the efforts to decrease UTI overdiagnosis and antibiotic overuse. Disclosures All Authors: No reported disclosures

Background Congenital syphilis (CS) rates have increased in the United States since 2013. Management of infants exposed to syphilis during pregnancy entails a detailed clinical evaluation, followed by stratified work-up and treatment. Methods During 2016─2021, 9,827 surveillance cases of CS were notified to the National Notifiable Diseases Surveillance System. Using the clinical framework described in the 2015 CDC Sexually Transmitted Diseases Treatment Guidelines, we assigned a clinical scenario (Proven or Highly Probable CS, Possible CS, CS Less Likely, and CS Unlikely) to 8,280 liveborn cases which had sufficient data for case classification (Figure 1). Based on data documented in the case report, we described the elements of evaluation and therapy provided to neonates, assessing whether they met, were in excess of, or were less extensive than recommendations, and stratified these findings by race, ethnicity, and geography. Results Of the 8,280 surveillance cases which were assigned a clinical scenario, the majority (80.9%) were classified as Possible CS, of whom 60.7% received an appropriate evaluation, while 68.4% received appropriate treatment. Of those assigned to Proven or Highly Probable CS, 46.0% received an appropriate evaluation, while 82.3% received appropriate treatment. By U.S. census region, infants born in the Northeast were most likely to receive evaluation (75.7%) and treatment (87.3%) at or above recommendations for their case scenario, while infants born in the South were least likely to receive at or above recommended evaluation (49.5%) and treatment (59.3%). Infants born to a birth parent reporting non-Hispanic Native Hawaiian/Pacific Islander race were most likely to report less than recommended evaluation (36.7%), while infants of a non-Hispanic Black birth parent were most likely to experience less than recommended treatment (32.2%). Conclusion This analysis of CS clinical scenarios underscores disparities in evaluation and therapy across geographic, racial, and ethnic lines. Further research is needed to understand factors involved in the evaluation and treatment of infants affected by CS, particularly for those born in the South and to birthing parents reporting minority racial and ethnic backgrounds. Disclosures All Authors: No reported disclosures

Background Candida auris is an emerging fungal pathogen which is often multidrug-resistant, can cause severe infections, and spreads readily in healthcare settings. While echinocandin resistance (ech-R) remains low in the United States (< 5%), the number has been increasing, which is concerning because echinocandins are first-line therapy for C. auris infections. In May 2022, the first ech-R C. auris isolate in Michigan was detected at long-term acute care hospital (LTACH) A and enhanced lab surveillance was conducted to assess potential for ech-R transmission. Methods Upon detection of C. auris in a urine specimen at LTACH A in March 2022, a containment response was initiated, which included clinical surveillance and colonization screening of patients at LTACH A. C. auris colonization screening testing and antifungal susceptibility testing (AFST) was performed at Wisconsin State Laboratory of Hygiene and whole genome sequencing (WGS) by the CDC. Ech-R was determined using tentative breakpoints defined by CDC. Results From Mar 2022 – Sept 2022, 15 C. auris-positive specimens were detected from 12 patients at LTACH A (5 clinical specimens, 10 screening swabs). In May 2022, AFST on a blood isolate from a C. auris-colonized patient showed resistance to azole and echinocandin classes. This patient had no history of prior echinocandins use. AFST conducted on 12 available isolates (5 clinical, 7 screening) detected ech-R in 10 (83%) isolates (3 clinical, 7 screening); all isolates were resistant to azoles and susceptible to polyenes. WGS was performed on 4 isolates and revealed 3 closely-related clade III isolates (all ech-R), suggesting possible facility transmission, and 1 clade IV isolate (susceptible), suggesting a separate introduction. Conclusion Multiple ech-R C. auris isolates detected among patients overlapping in the same facility and with close genetic relatedness provide further evidence that echinocandin resistant strains can be transmitted among patients and raise concerns about spread to a larger population of patients without prior echinocandin use. Enhanced surveillance for C. auris detection and antifungal resistance, public health reporting, and robust infection prevention and control measures are critical to containing the spread of concerning resistance. Disclosures All Authors: No reported disclosures

Background People with immunocompromising conditions (IC) are at increased risk of severe COVID-19 and death. These individuals show weaker immunogenicity following vaccination than individuals without IC, yet immunogenicity after SARS-CoV-2 infection is poorly understood. To address this gap, the presence of infection-induced antibodies in sera following a positive COVID-19 test result was compared between people with and without IC. Methods Data were from CDC’s national commercial laboratory seroprevalence study, a repeated, cross-sectional survey that includes associated diagnostic codes and previous COVID-19 viral test results. Infection-induced antibody seroprevalence in sera from people with a positive COVID-19 test result was compared by IC status for three post-infection periods: 14–90 (early), 91–180 (mid), and >180 (late) days. A logistic regression produced adjusted odds ratios (aOR) comparing infection-induced antibody prevalence among specimens with and without associated IC adjusted for age, sex, and infection-induced antibody assay used (Abbott Architect, Ortho VITROS, or Roche Elecsys). Results The analytic sample consisted of 15,554 specimens across the three periods (4,571 early, 4,465 mid, and 6,518 late). Of these, 188, 157, and 283 specimens had one or more associated, recorded IC, respectively. During the early period, 22.3% of specimens with IC lacked infection-induced antibodies compared with 6.8% of those without IC. After adjustment, specimens with IC were more likely to lack infection-induced antibodies in the early (aOR: 4.85; 95% CI: 3.20–7.38), mid (aOR: 2.53; 95% CI:1.57–4.09), and late (aOR:1.62; 95% CI:1.12–2.36) periods compared to specimens without IC. Conclusion Sera from people with IC is less likely to contain infection-induced antibodies following SARS-CoV-2 infection compared to sera from those without IC within the studied periods. These findings stress the importance of prevention measures for people with IC, such as pre-exposure prophylaxis, additional vaccination doses, and consistent mask use before and after a documented infection. Disclosures All Authors: No reported disclosures

Background Delays in TB treatment prolong the period of infectivity and are associated with drug resistance. Tajikistan has a high and increasing burden of multidrug-resistant tuberculosis (incidence of 28/100,000 in 2021). Many new cases present with severe disease, indicating delayed care. The COVID-19 pandemic further threatened to undo progress. Methods We conducted a retrospective cohort study of people >15 years old newly diagnosed with pulmonary TB in Dushanbe in 2019-2021. We conducted face-to-face interviews using structured questionnaires and abstracted data from medical records. We defined patient-delay as >14 days between TB symptom onset and initial visit, and provider-delay as >3 days from initial visit to treatment initiation. We ran multivariable Poisson regressions to estimate variables associated with presentation-delay and provider-delay. Results From 2019-21, 472 people were newly diagnosed with pulmonary TB. Of these, 82% had delayed treatment, 49% were male, 61% had lung tissue decay, 11% had diabetes, and 4% had HIV. Additionally, 42% had been diagnosed in 2019. The proportion with patient-delay was similar before and during the pandemic (83% vs. 82%, respectively, p=0.8). However, the proportion with provider-delay was higher before than during the pandemic (44% vs. 34%, p=0.02). There was no statistical difference in median days of patient-delay before (60 days; interquartile range [IQR]: 15–541) and after (60 days; IQR: 15–360, p=0.6) the pandemic, nor in median days of provider-delay before (7 days; IQR: 4–336) and after (7 days; IQR: 4–225, p=0.6) the pandemic. In multivariable analysis, the COVID-19 pandemic was not associated patient-delay (adjusted risk ratio and 95% confidence interval=1.00; 0.96-1.04). Patient-delay was significantly higher in people who ignored disease symptoms (1.41; 1.20-1.65) and thought services were expensive (1.10; 1.01-1.20) even though they are free of charge (Table 1). Conclusion Contrary to expected, presentation-delay for TB diagnosis did not differ before and during the COVID-19 pandemic, and provider-delay was lower. Increased vigilance of respiratory diseases and differential diagnosis for SARS-CoV-2 may have resulted in timelier TB diagnosis. However, interventions to further reduce delays are still needed. Disclosures All Authors: No reported disclosures

Background COVID-19 vaccines are safe and effective. Rapid rollout of vaccines reduced COVID-19 morbidity and mortality globally. Pharmacovigilance systems have ensured safety of these vaccines. Well-functioning vaccine safety surveillance builds public confidence in vaccine programs, but these systems may be lacking in limited-resource settings. To identify gaps in pharmacovigilance surveillance, we conducted an evaluation in Khojaly District, Uzbekistan, with population of 120 thousand people. Methods We reviewed regulatory documents related to COVID-19 vaccination and registration of side effects after immunization. We also conducted a survey in April 2022 of 30 healthcare providers in 5 of 10 polyclinics in Khojaly districts whose responsibilities included vaccination of the population. The survey asked about their knowledge and practices related to adverse events following immunization (AEFI). AEFI was defined as any health condition that occurs after immunization and does not necessarily have a causal relationship with vaccination. Results From April 2021 to March 2022, 78,453 doses of COVID-19 vaccines were given in Khojaly district. Of these, 70% of doses were from ZF-UZ-VAC-2001 (Zifivax) vaccine doses, an adjuvanted protein produced in Uzbekistan (Table 1), 9% Pfizer–BioNTech vaccine doses and 7% Moderna vaccine doses. All AEFIs are mandatorily reported by providers (Figure 1). Of 2,464 reported AEFI, majority (75%) were procedural errors, 1% were mild allergic reactions, and only 2 cases of anaphylactic shock. Among healthcare providers surveyed (Table 2), 33% did not know where to report the AEFI and 10% reported large patient load as a barrier to reporting. Half (50%) of providers had encountered a case of AEFI following COVID-19 vaccination, 10% encountered a severe AEFI, and 43% submitted an AEFI report. In record review, we identified cases of AEFI that had only been registered in patient medical charts, and not reported into the AEFI surveillance system. Diagram of AEFI surveillance for COVID-19 vaccines in Uzbekistan COVID-19 vaccine doses and reported AEFI, Khojaly district, Uzbekistan, 2021-22 Knowledge of AEFI and AEFI reporting among COVID-19 vaccine providers, Khojaly district, Uzbekistan, 2021-22 Conclusion Important considerations were identified in COVID-19 pharmacovigilance surveillance. The system can be strengthened through increased training of healthcare providers in standard operating procedures for identifying, reporting and investigation AEFI cases associated with COVID-19 vaccines. Disclosures All Authors: No reported disclosures

Background Social vulnerability impacts the transmission of SARS-CoV-2 (SCV2) among household contacts. Understanding these correlates can inform interventions to prevent infection among close contacts. We examined whether the social vulnerability index (SVI), a composite measure of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation, is associated with the risk of SCV2 infection among household contacts. Overall Social Vulnerability Index Diagram Methods We used data from a multi-site, prospective, case-ascertained household transmission study with daily nasal swabs for 10 days and RT-PCR testing to detect SCV2 infections in household contacts. Age and gender were self-reported and vaccination status was self-reported and verified. We mapped households to 2020 census tracts and the 2020 SVI (Figure 1). We examined the association between census tract-level SVI (in quartiles) and the risk of infection among household contacts using Poisson regression with generalized estimating equations, accounting for household clustering. Inclusion criteria for analysis in this study. Inclusion criteria for analysis in this study. Results Among 1,171 household contacts from 719 households, 67.4% developed SCV2 infection. After adjusting for the age of the contact and study site, contacts living in the most vulnerable SVI quartiles, Q3 (Incidence Rate Ratio [IRR] 1.19, 95% CI 1.01-1.40) and Q4 (IRR=1.18, 95% CI 1.00-1.40), had higher rates of infection compared to those living in the least vulnerable quartile (Q1) at the census tract level. To describe the effect of SVI accounting for vaccination, we performed a second regression adjusting for vaccine receipt among participants. We found that Q3 (IRR 1.19, 95% CI 1.01-1.40) still had higher rates of infection compared to those living in the least vulnerable quartile (Q1). Q4 was directionally consistent but confidence bounds crossed 1 (IRR=1.17, 95% CI 0.99-1.39). Conclusion Household contacts from census tracts with greater social vulnerability at the census tract level had a greater risk of SCV2 infection. These risks held even after accounting for vaccine receipt among participants. Future public health interventions should focus on reducing infection and transmission among individuals living in areas with higher social vulnerability beyond vaccination coverage. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member

Background In July 2022, the Chicago Department of Public Health (CDPH) was notified of four residents with Elizabethkingia (Ek) infections at a ventilator-capable skilled nursing facility (vSNF A). The facility reviewed microbiology records, identified six additional cases and CDPH initiated an investigation. Methods A case-patient was defined as a resident at vSNF A with Ek spp. identified from a clinical specimen. Information was collected via case report form regarding risk factors for Ek infection. Site visits were conducted to observe dialysis, wound care practices, and water disruption. Environmental and clinical isolates were sequenced by the CDC to assess genetic relatedness. Results January 2021-2023, 14 case-patients were identified with Ek infection: 11 bacteremias, two pneumonias, and one had both. Two case-patients died. Nine case-patients were hemodialyzed, six required ventilator support, and all case-patients had decubitus ulcers. Seven had exposures to tap-water during care. Site visits revealed potential exposure through bathing or healthcare worker hands contaminated by tap-water, personal items on sink-tops, and sterile supplies stored by sinks. Water quality parameters verified chlorine levels above minimum standards by the Illinois Pollution Control Board. Among environmental samples collected, E. anophelis was isolated from first-catch water in the room of a ventilated case-patient. Whole genome sequencing indicated this isolate was closely related to the clinical isolate of the case-patient in the room and a case-patient on a different floor. Both patients were hemodialyzed and exposed to tap-water for bathing. Conclusion Infection control recommendations included avoiding tap-water for bathing, not disposing body-fluid in sinks, routine flushing, disinfecting or removing aerators, and disinfecting sink drains with scheduled foaming disinfectant application. This investigation demonstrates a persistent outbreak of Ek in a vSNF population, likely related to contaminated tap-water. We postulate that Elizabethkingia persisted in water system biofilms, despite measurable chlorine levels, leading to patient exposure by contaminated healthcare worker hands or through tap water bathing in the presence of decubitus ulcers. Disclosures All Authors: No reported disclosures

Background The COVID-19 pandemic highlighted the potential pathogenicity of betacoronaviruses. This elucidates the need to further investigate human coronaviruses (HCoV), which includes both alpha and betacoronaviruses, to better understand their seasonality and severity among children. Methods The New Vaccine Surveillance Network (NVSN) enrolled children at 7 pediatric medical centers in the United States seen at the emergency department (ED) or hospitalized with acute respiratory infection (ARI), during 12/1/2016–9/28/2020. Respiratory specimens were collected and tested using real-time reverse transcription polymerase-chain reaction assays. The frequency of seasonal HCoV (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) detections was measured and symptoms were reported by parent interview. Descriptive statistics were performed to compare HCoV-positive inpatients to those seen in the ED. SARS-CoV-2 infections were excluded. Results Of 34,455 children enrolled, 925 (2.7%) were positive for HCoV, of which 398 (43%) were inpatients and (57%) were ED patients (Table). 346 detections (37.4%) were HCoV-OC43, 298 (32.3%) HCoV-NL63, 186 (20.2%) HCoV-HKU1, and 107 (11.6%) HCoV-229E. More than one coronavirus was detected in 12 children (1.3%). HCoV were primarily detected between October and April of each season; 1 to 2 types dominated each year but not consecutively (Figure). Among HCoV-positive children, 527 (57.0%) received their highest level of care in the ED while 398 (43.0%) were hospitalized. HCoV-229E was the most common HCoV detected among inpatients (57.0%), followed by HCoV-HKU1-(45.2%); HCoV-OC43- (40.8%); and HCoV-NL63 (38.9%). Among those positive for a HCoV age, race, and insurance status were significantly associated with hospitalization. Conclusion HCoV followed a winter-season circulation pattern, but with variation in the predominant type across years. HCoV-OC43 accounted for the largest number of HCoV infections whereas HCoV-229E had the highest proportion hospitalized. Further surveillance is required to evaluate the impact of the emergent circulation of SARS-CoV-2 on seasonal HCoVs. Disclosures Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support Geoffrey A. Weinberg, MD, Merck & Co: Honoraria Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Pedro A. Piedra, MD, Ark Bioscience: Advisor/Consultant|Ark Bioscience: Grant/Research Support|GSK: Grant/Research Support|Icosavax: Advisor/Consultant|Icosavax: Grant/Research Support|Mapp Biologics: Grant/Research Support|Meissa Vaccines: Grant/Research Support|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Novavax: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Takeda: Advisor/Consultant Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support

Background Although clinical applications of SARS-CoV-2 antibody tests during the COVID-19 pandemic were limited to identifying recent/prior infection, how these tests were used for clinical management of COVID-19 patients is unknown. We consider US infectious disease (ID) physicians’ perceptions about SARS-CoV-2 antibody tests to inform preparedness for future events. Methods In March 2022, we surveyed members of the Emerging Infections Network (EIN), a national network of ID physicians on use of SARS-CoV-2 antibody assays, interpretation of results, and clinical scenarios for which such tests were considered. We analyzed comments provided in a free text field for key themes. Results Overall, 96 respondents provided non-mutually exclusive free-text comments. Fourteen used serology to assess patients with suspected MIS-C. Another 8 used serology in individuals with immunocompromising conditions, including organ transplant recipients and those with human immunodeficiency virus (HIV) infection, for example, when making decisions to utilize anti-SARS-CoV-2 mAbs (available at the time of the survey but no longer authorized for PReP or treatment.) Twenty-one respondents shared that the most important need for SARS-CoV-2 antibody assays was to discern a correlate of immune protection. Twenty-six considered that serology was not useful for clinical decision-making, and 23 recognized the limitations of the antibody tests, called for more studies, and indicated that additional guidance would be beneficial, noting for example, “Many clinicians order antibody tests but have no idea how to interpret or misinterpret, so guidelines on usage and when not to use would be extremely helpful.” Conclusion This analysis provides historical insights into challenges practicing ID physicians faced in the midst of a pandemic. During March 2022, some respondents reported use of SARS-CoV-2 antibody assays including when making treatment decisions. As diagnostic and treatment modalities continue to evolve, federal agencies, medical societies, and academic partners can consider providing guidance on appropriate use of novel tests in clinical practice for near term and future responses. Disclosures Philip M. Polgreen, MD, Eli Lilly: Case adjudication for a clinical trial

Background Persons with respiratory viral infections (RVI) may shed detectable virus after symptom recovery. Duration of detection by molecular methods is not well described for non-SARS-CoV-2 respiratory viruses. Methods School KIDS is a prospective respiratory viral surveillance program in a Missouri school district. Participating students and staff with RVI symptoms can receive respiratory viral testing using self-collected nasal swabs. Symptomatic participants with detectable virus(es) on primary swabs were scheduled to receive 2 convalescent swabs weekly after initial test during weekly school surveillance testing. All convalescent tests performed within 21 days of the primary specimen were included. Only participants providing ≥ 1 convalescent swab were included. Specimens were tested using Hologic® Panther Fusion® or QIAstat-Dx PCR assays that included adenovirus (AdV); seasonal coronaviruses (sCoV) 229E, HKU1, NL63, OC43; human metapneumovirus, influenza A and B (Flu), parainfluenza viruses 1-4, respiratory syncytial virus, rhinovirus/ enterovirus (RV/EV), and SARS-CoV-2. We used survival analysis to quantify median number of days until individuals tested negative for each virus. Results From November 3, 2022 – April 14, 2023, 344 symptomatic participants (141 preK/elem, 49 middle, 22 high, 132 staff) submitted 586 primary specimens; 292 (50%) were positive for a virus. For positive primary specimens, median [IQR] time of symptom onset to specimen collection was 2 [1,3] days. A total of 320 viruses were detected; most common were RV/EV (37%) and sCoVs (25%) (Table). An additional 370 convalescent specimens were collected (87 specimens on days 1-7 following primary positive; 166 specimens on days 8-14; and 117 specimens on days 15-21). Median number of days [95% confidence interval] when repeat convalescent tests became negative varied by virus (AdV 15 [11,undefined] days, Flu A 14 [9,19] days, RV/EV 12 [11,14] days, SARS-CoV-2 14 [14,17] days, sCoV 10 [9,12] days) (Figure).Table.Characteristics of primary positive and convalescent testing (i.e. ongoing positivity) of nasal swabs from preK—12 grade students and staff with respiratory symptoms—Missouri, November 2022 -April 2023Figure.Cumulative probability of testing negative for a respiratory virus on subsequent respiratory viral testing Conclusion Students and staff continued to have detectable virus by nasal swabs 10-15 days after symptomatic positive specimen. Further data are needed to determine when participants are no longer infectious. Disclosures Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support

Background Understanding the transmissibility of respiratory viruses by symptoms is important for public health. Methods Persons who tested positive for SARS-CoV-2 and their household contacts (HHC) were recruited from 7 US sentinel sites or by remote invitation nationwide during Sep. 2021—Mar. 2023. The household primary case was the person with the earliest symptom onset or positive test. Starting ≤6 days after primary case onset, primary cases and HHC completed symptom logs (daily, retrospective since onset and for 10 days post-enrollment) and collected nasal or saliva specimens (daily for 10 days) that were tested by RT-PCR. Infected individuals were counted as having developed fever, lower respiratory symptoms (LRS: wheezing, chest tightness/pain, shortness of breath, cough), other symptoms (fatigue, aches, abdominal pain, diarrhea, vomiting, change of taste/smell, headache, sore throat, runny nose, nasal congestion), or as being asymptomatic based on all logs. Risk of secondary infection (any PCR positivity) among eligible, tested HHC (Methods 1) by symptoms of primary cases was estimated using Poisson regression with generalized estimating equations. We estimated days from onset to last PCR positive in a survival model. Methods upload 1. Enrolled and analytically included household members in case-ascertained studies of household transmission of SARS-CoV-2, United States, Sept 2021 - Mar 2023. Results This analysis included 842 households (839 primary cases, 836 infected HHC, and 615 uninfected HHC, median household size of 2). Most primary cases (99%) and infected HHC (81%) were symptomatic (Results 1). Primary cases had higher frequencies of fever or LRS than infected HHC (Results 2). HHC exposed to primary cases who developed fever or LRS were more likely to become infected than HHC exposed to primary cases who did not have fever or LRS (Results 3). Post-hoc comparisons by individual symptoms supported this for fever and all LRS but chest pain (fever: IRR 1.31 95% CI: 1.13-1.52; cough: IRR 1.54 95% CI 1.21 – 1.95; wheezing: IRR 1.20 95% CI 1.08 – 1.35; shortness of breath IRR 1.15, 95% CI 1.04 – 1.27). Primary cases with fever or LRS were PCR positive for a median of 14 days (95% CI: 14 – 15) post-onset, compared to 10 days (95% CI: 9 – 11) for cases who did not have fever or LRS. Results upload 1. Characteristics of included household members in case-ascertained studies of household transmission of SARS-CoV-2, United States, Sep 2021 - Mar 2023. Results upload 2. Proportion of primary cases and infected household contacts who experienced individual symptoms. Results upload 3. Unadjusted and adjusted risk of household contacts becoming infected with SARS-CoV-2, by symptoms in the primary case. Conclusion Contacts of primary cases with fever or lower respiratory symptoms may have been more likely to become infected than contacts of primary cases without, suggesting higher transmissibility. Disclosures Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support

Background SARS-CoV-2 Omicron variants have increased vaccine-induced immune evasion and their emergence coincided with waning COVID-19 vaccine effectiveness (VE). The duration of immunity from the primary series and VE of booster doses against pediatric COVID-19 (Omicron)-associated hospitalizations has not been characterized in the United States. Methods Using a case-control design, we examined VE against laboratory-confirmed COVID-19-associated hospitalizations, enrolling case-patients hospitalized for COVID-19 and SARS-CoV-2 test-negative controls with COVID-like illness from 31 hospitals in 23 states. VE was estimated through multivariable logistic regression by comparing the odds of antecedent primary series or booster COVID-19 mRNA vaccination within and beyond 60 days prior to hospitalization. Results were analyzed by age group (5–11 and 12–18 years) among patients admitted December 19, 2021–March 30, 2023. Results We enrolled 1,242 case-patients (972 [78%] of whom were unvaccinated, 164 [13%] of whom received life support, and 11 of whom died) and 1,309 controls. Among children aged 5-18 years, VE of 2 mRNA doses (complete primary series) against pediatric COVID-19 hospitalization was 64% (95% confidence interval [CI]: 44–76%) at 14-60 days after dose 2 (median time since dose 2, 38 days); VE waned to 38% (95% CI: 23–50%) at ≥60 days (median time since vaccination, 213 days). Within 60 days of a monovalent booster dose, VE was 52% (95% CI: -3–77%); among children aged 5-11 years, VE of a bivalent booster dose was 79% (95% CI: 25-94%). Among case-patients who required life support or died, 122/164 (74%) were unvaccinated and only 3 (2%) had received a bivalent booster dose.Figure 1.Vaccine effectiveness against COVID-19-related hospitalizations, by age group, vaccine dose, and time since last dose. VE estimates were only plotted if confidence interval width was <200. Adjusted models included ≥1 underlying medical condition (yes/no), age in years, census region, biweekly date of hospital admission, and social vulnerability index (SVI) score. Sex and race/ethnicity were tested as confounders in the full model but were dropped for absence of evidence of confounding.Table 1.Critical outcomes among enrolled COVID-19 case-patients ages 5-18 years, by vaccine dose and time since last vaccine dose. Abbreviations: ICU, intensive care unit; ECMO, extracorporeal membrane oxygenation Conclusion COVID-19 mRNA vaccination reduced the likelihood of pediatric COVID-19 hospitalization by >60%; VE waned but remained protective, even at a median of 213 days after dose 2. Although not reaching statistical significance due to limited power, monovalent boosters appeared to temporarily restore protection, and bivalent booster doses among 5–11-year-olds were nearly 80% protective against hospitalization. Nearly three quarters of children requiring life support or who died were unvaccinated. Disclosures Regina Simeone, PhD, Pfizer: Stocks/Bonds Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support