BACKGROUND: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days. METHODS: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment. Participants completed a follow-up survey 90 days after enrollment to characterize ongoing symptoms. RESULTS: We analyzed 1967 participants enrolled between December 2021 and May 2023. The risk of ongoing symptoms did not differ by infection status in SCV2 (SCV2-positive: 15.6%; SCV2-negative: 13.9%; odds ratio [OR]: 1.14; 95% CI: .7-1.69) or influenza (influenza-positive: 8.8%; influenza-negative: 10.0%; OR: .87; 95% CI: .45-1.72) households. However, among study participants with a documented infection, SCV2-positive participants had nearly twice the odds of ongoing symptoms as influenza-positive participants (OR: 1.92; 95% CI: 1.27-2.97). CONCLUSIONS: These results suggest that SCV2 households have a significantly higher prevalence of ongoing symptoms compared with influenza households (OR: 1.78; 95% CI: 1.28-2.47). Among participants with SCV2 infection, underlying conditions (adjusted OR [aOR]: 2.65; 95% CI: 1.80-3.90) and coronavirus disease 2019 (COVID-19)-like symptoms (aOR: 2.92; 95% CI: 1.15-7.43) during acute infection increased odds of ongoing symptoms at 90 days, whereas hybrid immunity reduced the odds of ongoing symptoms (aOR: 0.44; 95% CI: .22-.90).

CONTEXT: Little is known about when and how the ICD-10-CM diagnosis code for Post-COVID Conditions (PCC; U09.9) is being used to document PCC. OBJECTIVES: To examine the use and characteristics of clinical coding for PCC. DESIGN: A retrospective cohort. SETTING: Transaction-level medical encounters, laboratory testing results, pharmacy claims, and medical claims for inpatient and outpatient care from the HealthVerity database. PARTICIPANTS: 382 400 US adults and children with private health insurance, Medicare, and Medicaid who had U09.9 code documented during October 1, 2021-June 30, 2023. OUTCOME MEASURES: Count of first use of the U09.9 code, (a) overall, over time, and proportion by provider type; (b) prevalence of PCC-associated incident conditions co-documented with U09.9; (c) number of documented SARS-CoV-2 infections preceding U09.9; (d) timing between infection and U09.9; (e) encounters during the 6 months following first use of U09.9. RESULTS: Overall, 0.6% of 65 556 068 patients had a PCC diagnosis code (64.6% female; 6 in 10 had ≥1 preexisting conditions). The highest count of new U09.9 codes occurred during Quarter 1 and Quarter 3 of 2022 and was documented by a variety of provider specialties. The most prevalent co-documented PCC-associated incident conditions were respiratory (13.4%) and malaise and fatigue (7.8%). Only 62% of patients had SARS-CoV-2 infection documented preceding U09.9; median time to PCC documentation was 17.0 days (interquartile range [IQR] = 5.0, 61.0). Patients with ≥1 encounters during which PCC was documented in the 6 months following their index encounter (n = 109 794) had, on average, 25.5 additional encounters (median = 14 [IQR = 7, 29]). CONCLUSIONS: Our study describes the sociodemographic characteristics, complex clinical manifestations, and high healthcare use of patients following a PCC diagnosis. These findings may inform efforts to identify and treat PCC, inform healthcare planning, and support efforts to educate clinicians about the definition of PCC and accurate application of the code.

IMPORTANCE: An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC). OBJECTIVE: To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection). EXPOSURES: COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available. MAIN OUTCOME AND MEASURES: Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children. RESULTS: A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69). CONCLUSIONS AND RELEVANCE: In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.

A global outbreak of clade II mpox associated with sexual contact, disproportionately affecting gay, bisexual, and other men who have sex with men (MSM), has been ongoing since May 2022. Information on types of contact most associated with transmission is limited. This report used data from a multijurisdictional vaccine effectiveness case-control study of sexually active persons aged 18-49 years who identified as MSM or transgender, collected during August 2022-July 2023. Odds of mpox associated with selected types of intimate and nonintimate close contact with a person with mpox were estimated. Among 457 case-patients and 1,030 control patients who met minimum data requirements, 150 (32.8%) case-patients and 57 (5.5%) control patients reported close contact with a person with mpox and were included in this analysis. Adjusted odds of mpox were 5.4 times as high among those who reported having condomless receptive anal sex with a person with mpox, compared with participants who reported close contact with a person with mpox and no condomless receptive anal sex with that person (OR = 5.4; p = 0.031). Although the mpox vaccine is highly effective, vaccination coverage remains low; a multifaceted approach to prevention remains important and should include vaccination promotion, safer sex practices, and increasing awareness that mpox continues to circulate.

BACKGROUND: Track PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection). METHODS: The study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection. DISCUSSION: These data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients.

INTRODUCTION: Long COVID encompasses a wide range of health problems that emerge, persist, or recur following acute COVID-19 illness. Given that the prevalence of self-reported Long COVID is highest among U.S. adults in their prime working years, it is important to identify unmet needs and gaps in healthcare access and coverage among working age adults. METHODS: Prevalences (95% CI) of health insurance coverage and access to care by Long COVID status were estimated among adults 18-64 years (n = 18,117), accounting for survey design and weighted to the U.S. non-institutionalized population in the 2022 National Health Interview Survey. Analyses were conducted in 2023. RESULTS: Overall, 3.7% (95% CI 3.4, 4.0) of respondents were experiencing Long COVID. Adults experiencing Long COVID were less likely to report being uninsured relative to adults not experiencing Long COVID (P=0.004); however, 49.0% (95% CI 43.2, 54.7) had high deductible health plans. Adjusting for sociodemographic characteristics, adults experiencing Long COVID were more likely to access healthcare compared to adults not experiencing Long COVID (P<0.01 for seeing a doctor, telemedicine appointments, ≥2 urgent care visits, ≥2 emergency department visits, and hospitalized overnight). Despite more frequent healthcare use, adults experiencing Long COVID were also more likely to abstain from and delay medical care, therapy, and prescriptions due to cost compared to adults not experiencing Long COVID (P<0.0001 for all comparisons). CONCLUSIONS: These findings may be used to inform healthcare planning for adults experiencing Long COVID and highlight the ongoing need to improve access and affordability of quality and comprehensive care.

BACKGROUND: Understanding the usefulness of additional COVID-19 vaccine doses-particularly given varying disease incidence-is needed to support public health policy. We characterize the benefits of COVID-19 booster doses using number needed to vaccinate (NNV) to prevent one COVID-19-associated hospitalization or emergency department encounter. METHODS: We conducted a retrospective cohort study of immunocompetent adults at five health systems in four U.S. states during SARS-CoV-2 Omicron BA.1 predominance (December 2021-February 2022). Included patients completed a primary mRNA COVID-19 vaccine series and were either eligible to or received a booster dose. NNV were estimated using hazard ratios for each outcome (hospitalization and emergency department encounters), with results stratified by three 25-day periods and site. FINDINGS: 1,285,032 patients contributed 938 hospitalizations and 2076 emergency department encounters. 555,729 (43.2%) patients were aged 18-49 years, 363,299 (28.3%) 50-64 years, and 366,004 (28.5%) ≥65 years. Most patients were female (n = 765,728, 59.6%), White (n = 990,224, 77.1%), and non-Hispanic (n = 1,063,964, 82.8%). 37.2% of patients received a booster and 62.8% received only two doses. Median estimated NNV to prevent one hospitalization was 205 (range 44-615) and NNV was lower across study periods for adults aged ≥65 years (110, 46, and 88, respectively) and those with underlying medical conditions (163, 69, and 131, respectively). Median estimated NNV to prevent one emergency department encounter was 156 (range 75-592). INTERPRETATION: The number of patients needed to receive a booster dose was highly dependent on local disease incidence, outcome severity, and patient risk factors for moderate-to-severe disease. FUNDING: Funding was provided by the Centers for Disease Control and Prevention though contract 75D30120C07986 to Westat, Inc. and contract 75D30120C07765 to Kaiser Foundation Hospitals.

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,(†) including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,(§) to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),(¶) regardless of administration route or immunocompromise status.

BACKGROUND: In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route. METHODS: We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100. RESULTS: Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1). CONCLUSIONS: In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.).

OBJECTIVES: We assessed BNT162b2 vaccine effectiveness (VE) against mild to moderate and severe coronavirus disease 2019 (COVID-19) in children and adolescents through the Omicron BA.4/BA.5 period. METHODS: Using VISION Network records from April 2021 to September 2022, we conducted a test-negative, case-control study assessing VE against COVID-19-associated emergency department/urgent care (ED/UC) encounters and hospitalizations using logistic regression, conditioned on month and site, adjusted for covariates. RESULTS: We compared 9800 ED/UC cases with 70 232 controls, and 305 hospitalized cases with 2612 controls. During Delta, 2-dose VE against ED/UC encounters at 12 to 15 years was initially 93% (95% confidence interval 89 to 95), waning to 77% (69% to 84%) after ≥150 days. At ages 16 to 17, VE was initially 93% (86% to 97%), waning to 72% (63% to 79%) after ≥150 days. During Omicron, VE at ages 12 to 15 was initially 64% (44% to 77%), waning to 13% (3% to 23%) after ≥150 days; at ages 16 to 17 VE was 31% (10% to 47%) during days 60 to 149, waning to 7% (-8 to 20%) after 150 days. A monovalent booster increased VE to 54% (40% to 65%) at ages 12 to 15 and 46% (30% to 58%) at ages 16 to 17. At ages 5 to 11, 2-dose VE was 49% (33% to 61%) initially and 41% (29% to 51%) after 150 days. During Delta, VE against hospitalizations at ages 12 to 17 was high (>97%), and at ages 16 to 17 remained 98% (73% to 100%) beyond 150 days; during Omicron, hospitalizations were too infrequent to precisely estimate VE. CONCLUSIONS: BNT162b2 protected children and adolescents against mild to moderate and severe COVID-19. VE was lower during Omicron predominance including BA.4/BA.5, waned after dose 2 but increased after a monovalent booster. Children and adolescents should receive all recommended COVID-19 vaccinations.

BACKGROUND: Data are limited on influenza testing among adults with acute respiratory illness (ARI)-associated hospitalizations. We identified factors associated with influenza testing in adult ARI-associated hospitalizations across the 2016-2017 through 2019-2020 influenza seasons. METHODS: Using data from 4 health systems in the United States, we identified hospitalizations that had an ARI discharge diagnosis or respiratory virus test. A hospitalization with influenza testing was based on testing performed within 14 days before through 72 hours after admission. We used random forest analysis to identify patient characteristics and influenza activity indicators that were most important in terms of their relationship to influenza testing. RESULTS: Across 4 seasons, testing rates ranged from 14.8%-19.4% at 3 pooled sites and 60.1%-78.5% at a fourth site with different testing practices. Discharge diagnoses of pneumonia or infectious disease of noninfluenza etiology, presence of ARI signs/symptoms, hospital admission month, and influenza-like illness activity level were consistently among the variables with the greatest relative importance. CONCLUSIONS: Select ARI diagnoses and indicators of influenza activity were the most important factors associated with influenza testing among ARI-associated hospitalizations. Improved understanding of which patients are tested may enhance influenza burden estimates and allow for more timely clinical management of influenza-associated hospitalizations.

BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at three sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and SARS-CoV-2-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: 86,732 ED/UC ARI-associated encounters (7,696 [9%] cases) and 16,805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI): 20-29%) and 25% (95%CI: 11-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; CI: -5-17%) or with immunocompromising conditions (4%, CI:-45-36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.

BACKGROUND: COVID-19 vaccination coverage remains lower in communities with higher social vulnerability. Factors such as SARS-CoV-2 exposure risk and access to health care are often correlated with social vulnerability and may therefore contribute to a relationship between vulnerability and observed vaccine effectiveness (VE). Understanding whether these factors impact VE could contribute to our understanding of real-world VE. METHODS: We used electronic health record data from seven health systems to assess vaccination coverage among patients with medically attended COVID-19-like illness. We then used a test-negative design to assess VE for 2- and 3-dose mRNA adult (≥18 years) vaccine recipients across Social Vulnerability Index (SVI) quartiles. SVI rankings were determined by geocoding patient addresses to census tracts; rankings were grouped into quartiles for analysis. RESULTS: In July 2021, primary series vaccination coverage was higher in the least vulnerable quartile than in the most vulnerable quartile (56% vs. 36%, respectively). In February 2022, booster dose coverage among persons who had completed a primary series was higher in the least vulnerable quartile than in the most vulnerable quartile (43% vs. 30%). VE among 2-dose and 3-dose recipients during the Delta and Omicron BA.1 periods of predominance was similar across SVI quartiles. CONCLUSIONS: COVID-19 vaccination coverage varied substantially by SVI. Differences in VE estimates by SVI were minimal across groups after adjusting for baseline patient factors. However, lower vaccination coverage among more socially vulnerable groups means that the burden of illness is still disproportionately borne by the most socially vulnerable populations.

CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome(†) (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network(§) determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits(¶) and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.

The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5-11, 12-15, and 16-17 years (1-3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12-17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19-associated hospitalization (4-6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5-11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations(†) among persons aged 5-17 years with COVID-19-like illness across 10 states during April 9, 2021-January 29, 2022,(§) to estimate VE using a case-control test-negative design. Among children aged 5-11 years, VE against laboratory-confirmed COVID-19-associated ED and UC encounters 14-67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16-17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19-associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12-17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16-17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19-associated hospitalization among children aged 5-11 years was 74% 14-67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12-17 years.

CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance(†) (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites(§) examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).(¶) Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits.