Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis.

BACKGROUND: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. METHODS: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. FINDINGS: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. INTERPRETATION: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. FUNDING: The Centers for Disease Control and Prevention.

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Influenza Vaccine Effectiveness Against Influenza A-Associated Emergency Department, Urgent Care, and Hospitalization Encounters Among US Adults, 2022-2023.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season: VISION Network.

BACKGROUND: During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant. METHODS: We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. RESULTS: Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44-52%) overall, 53% (95% CI, 47-58%) among children aged 6 months-4 years, and 38% (95% CI, 30-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6-61%) overall, 56% (95% CI, 23-75%) among children ages 6 months-4 years, and 46% (95% CI, 2-70%) among those 5-17 years. CONCLUSIONS: During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.

Clinical Epidemiology and Risk Factors for Critical Outcomes Among Vaccinated and Unvaccinated Adults Hospitalized With COVID-19-VISION Network, 10 States, June 2021-March 2023.

BACKGROUND: The epidemiology of coronavirus disease 2019 (COVID-19) continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of COVID-19 hospitalizations and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023. We evaluated changes in demographics, clinical characteristics, and critical outcomes (intensive care unit admission and/or death) and evaluated critical outcomes risk factors (risk ratios [RRs]), stratified by COVID-19 vaccination status. RESULTS: A total of 60 488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, and critical outcomes declined from 24.8% to 19.4% (all P < .001) between the Delta (June-December, 2021) and post-BA.4/BA.5 (September 2022-March 2023) periods. Hospitalization events with critical outcomes had a higher proportion of ≥4 categories of medical condition categories assessed (32.8%) compared to all hospitalizations (23.0%). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated: adjusted RR, 2.27 [95% confidence interval {CI}, 2.14-2.41]; vaccinated: adjusted RR, 1.73 [95% CI, 1.56-1.92]) across periods. CONCLUSIONS: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time, and median patient age increased with time. Multimorbidity was most strongly associated with critical outcomes.

Reduced Risk of SARS-CoV-2 Infection Among Household Contacts with Recent Vaccination and Past COVID-19 Infection: Results from Two Multi-Site Case-Ascertained Household Transmission Studies.

Households are a primary setting for transmission of SARS-CoV-2. We examined the role of prior SARS-CoV-2 immunity on the risk of infection in household close contacts. Households in the United States with an individual who tested positive for SARS-CoV-2 during September 2021-May 2023 were enrolled if the index case's illness began ≤6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. The effects of prior SARS-CoV-2 immunity (vaccination, prior infection, or hybrid immunity) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Of 1,532 contacts (905 households), 8% had immunity from prior infection alone, 51% from vaccination alone, 29% hybrid immunity, and 11% had no prior immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The adjusted risk of SARS-CoV-2 infection was lowest among contacts with vaccination and prior infection (aRR: 0.81, 95% CI: 0.70, 0.93, compared with contacts with no prior immunity) and was lowest when the last immunizing event occurred ≤6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). In high-transmission settings like households, immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection.

Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.

BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

Antibiotic use and class absenteeism in children with influenza-like-illness in an emergency department.

BACKGROUND: Children with influenza-like-illness (ILI) often require clinician clearance or antibiotics to return to child care or school. Study objectives were to examine the association between antibiotic receipt during an Emergency Department (ED) visit for ILI and the outcomes of class absenteeism and illness duration. METHODS: A secondary analysis of 251 children aged 2 months to 12 years with uncomplicated ILI discharged from the ED from December 1, 2018 to November 30, 2019 was conducted. The primary exposure was receipt of antibiotics over the course of illness (assessed by chart review and family follow-up survey). RESULTS: Patients prescribed antibiotics (n = 65) experienced a median of 3 (interquartile range [IQR]: 1,5) days of class missed and 5 (IQR: 3,7) days of illness compared to 2 (IQR: 1,4) days of class missed and 4 (IQR: 3,7) days of illness for those not prescribed antibiotics (n = 186, p = 0.08 and p = 0.13, respectively). There was no statistically significant association with missed class days (incidence rate ratio [IRR]: 1.14 [0.86-1.50], p = 0.37) or days of illness (IRR: 1.06 [0.88-1.27], p = 0.55) for patients prescribed antibiotics compared to patients not prescribed antibiotics for ILI. CONCLUSIONS: Antibiotic use for ILI was not associated with reduced class absenteeism or illness duration. IMPACT STATEMENT: Child care centers and schools sometimes exclude children with influenza-like-illness (ILI) from class until cleared to return by a clinician and/or prescribed antibiotics. This study addresses these social drivers of overprescribing. Antibiotics were prescribed in 26% of children with ILI discharged from a large Emergency Department in the US. Antibiotic use was not significantly associated with class absenteeism or illness duration. This study can serve as a discussion point for clinicians when navigating parental or social pressures to prescribe antibiotics for uncomplicated acute respiratory tract infections, particularly when these pressures are influenced by concerns about returning to class.

SARS-CoV-2 Viral Shedding and Rapid Antigen Test Performance - Respiratory Virus Transmission Network, November 2022-May 2023.

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test).

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.

Vaccine Effectiveness Against Influenza-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2021-2022 Season, VISION Network.

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 3 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: In total, 86 732 ED/UC ARI-associated encounters (7696 [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%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 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.

Protection of Two and Three mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized With COVID-19-VISION Network, August 2021 to March 2022.

BACKGROUND: We assessed coronavirus disease 2019 (COVID-19) vaccination impact on illness severity among adults hospitalized with COVID-19, August 2021-March 2022. METHODS: We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing. We calculated odds ratios (ORs) for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation. RESULTS: We included 27 149 SARS-CoV-2-positive hospitalizations. During both Delta- and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR, 0.52 [95% CI, .28-.96]; Omicron OR, 0.69 [95% CI, .54-.87]). During both periods, risk of in-hospital death was lower among vaccinated compared with unvaccinated patients but ORs overlapped across vaccination strata. We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients. CONCLUSIONS: COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.

Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Relationships Between Social Vulnerability and Coronavirus Disease 2019 Vaccination Coverage and Vaccine Effectiveness.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination coverage remains lower in communities with higher social vulnerability. Factors such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure risk and access to healthcare 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 7 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 messenger RNA (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.

Respiratory Syncytial Virus, Influenza, and Coronavirus Disease 2019 Hospitalizations in Children in Colorado During the 2021-2022 Respiratory Virus Season.

OBJECTIVE: To compare demographic characteristics, clinical features, and outcomes of children hospitalized with respiratory syncytial virus (RSV), influenza, or severe acute respiratory syndrome coronavirus 2 during their cocirculation 2021-2022 respiratory virus season. METHODS: We conducted a retrospective cohort study using Colorado's hospital respiratory surveillance data comparing coronavirus disease 2019 (COVID-19)-, influenza-, and RSV-hospitalized cases < 18 years of age admitted and undergoing standardized molecular testing between October 1, 2021, and April 30, 2022. Multivariable log-binomial regression modeling evaluated associations between pathogen type and diagnosis, intensive care unit admission, hospital length of stay, and highest level of respiratory support received. RESULTS: Among 847 hospitalized cases, 490 (57.9%) were RSV associated, 306 (36.1%) were COVID-19 associated, and 51 (6%) were influenza associated. Most RSV cases were <4 years of age (92.9%), whereas influenza hospitalizations were observed in older children. RSV cases were more likely to require oxygen support higher than nasal cannula compared with COVID-19 and influenza cases (P < .0001), although COVID-19 cases were more likely to require invasive mechanical ventilation than influenza and RSV cases (P < .0001). Using multivariable log-binomial regression analyses, compared with children with COVID-19, the risk of intensive care unit admission was highest among children with influenza (relative risk, 1.97; 95% CI, 1.22-3.19), whereas the risk of pneumonia, bronchiolitis, longer hospital length of stay, and need for oxygen were more likely among children with RSV. CONCLUSIONS: In a season with respiratory pathogen cocirculation, children were hospitalized most commonly for RSV, were younger, and required higher oxygen support and non-invasive ventilation compared with children with influenza and COVID-19.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5-11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99-15.08]), new cough (aOR: 2.38, [95% CI: 1.69-3.36]), headache (aOR: 1.90, [95% CI: 1.28-2.81), fever (aOR: 1.83, [95% CI: 1.29-2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75-6.97]), or household contact (aOR: 2.66, [95% CI: 1.96-3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.

Safety of intravenous lacosamide in hospitalized children and neonates.

OBJECTIVE: Seizures are common in critically ill children and neonates, and these patients would benefit from intravenous (IV) antiseizure medications with few adverse effects. We aimed to assess the safety profile of IV lacosamide (LCM) among children and neonates. METHODS: This retrospective multicenter cohort study examined the safety of IV LCM use in 686 children and 28 neonates who received care between January 2009 and February 2020. RESULTS: Adverse events (AEs) were attributed to LCM in only 1.5% (10 of 686) of children, including rash (n = 3, .4%), somnolence (n = 2, .3%), and bradycardia, prolonged QT interval, pancreatitis, vomiting, and nystagmus (n = 1, .1% each). There were no AEs attributed to LCM in the neonates. Across all 714 pediatric patients, treatment-emergent AEs occurring in >1% of patients included rash, bradycardia, somnolence, tachycardia, vomiting, feeling agitated, cardiac arrest, tachyarrhythmia, low blood pressure, hypertension, decreased appetite, diarrhea, delirium, and gait disturbance. There were no reports of PR interval prolongation or severe cutaneous adverse reactions. When comparing children who received a recommended versus a higher than recommended initial dose of IV LCM, there was a twofold increase in the risk of rash in the higher dose cohort (adjusted incidence rate ratio = 2.11, 95% confidence interval = 1.02-4.38). SIGNIFICANCE: This large observational study provides novel evidence demonstrating the tolerability of IV LCM in children and neonates.

Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months-5 Years - VISION Network, United States, July 2022-June 2023.

On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5 years (Moderna) based on safety, immunobridging, and limited efficacy data from clinical trials. On December 9, 2022, CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months. mRNA COVID-19 vaccine effectiveness (VE) against emergency department or urgent care (ED/UC) encounters was evaluated within the VISION Network during July 4, 2022-June 17, 2023, among children with COVID-19-like illness aged 6 months-5 years. Among children aged 6 months-5 years who received molecular SARS-CoV-2 testing during August 1, 2022-June 17, 2023, VE of 2 monovalent Moderna doses against ED/UC encounters was 29% (95% CI = 12%-42%) ≥14 days after dose 2 (median = 100 days after dose 2; IQR = 63-155 days). Among children aged 6 months-4 years with a COVID-19-like illness who received molecular testing during September 19, 2022-June 17, 2023, VE of 3 monovalent Pfizer-BioNTech doses was 43% (95% CI = 17%-61%) ≥14 days after dose 3 (median = 75 days after dose 3; IQR = 40-139 days). Effectiveness of ≥1 bivalent dose, comparing children with at least a complete primary series and ≥1 bivalent dose to unvaccinated children, irrespective of vaccine manufacturer, was 80% (95% CI = 42%-96%) among children aged 6 months-5 years a median of 58 days (IQR = 32-83 days) after the dose. All children should stay up to date with recommended COVID-19 vaccines, including initiation of COVID-19 vaccination immediately when they are eligible.