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      Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus–Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season — New Vaccine Surveillance Network, October 2023–February 2024

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      , MD 1 , , , MPH 1 , , MPH 1 , , MD 2 , 3 , , MD 4 , 5 , , MD 6 , , MD 7 , , MD 8 , 9 , , MD 10 , , PhD 11 , , MD 2 , 3 , , PhD 4 , 5 , , MD 6 , , PhD 7 , , MD 8 , 9 , , MD 10 , , MD 12 , , MPH 1 , , MPH 2 , 3 , , MD 4 , 5 , , MD 6 , , MD 7 , , MBA 9 , , MPH 10 , , PhD 12 , , MPH 1 , , MPH 1 , , MPH 1 , New Vaccine Surveillance Network Product Effectiveness Collaborators, , MD 1 , * , , MD 1 , * New Vaccine Surveillance Network Product Effectiveness Collaborators, , , , , , , , , , , , , ,
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          The burden of respiratory syncytial virus infection in young children.

          The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric offices from 2002 through 2004. RSV was detected by culture and reverse-transcriptase polymerase chain reaction. Clinical information was obtained from parents and medical records. We calculated population-based rates of hospitalization associated with RSV infection and estimated the rates of RSV-associated outpatient visits. Among 5067 children enrolled in the study, 919 (18%) had RSV infections. Overall, RSV was associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most of the children had no coexisting illnesses. Only prematurity and a young age were independent risk factors for hospitalization. Estimated rates of RSV-associated office visits among children under 5 years of age were three times those in emergency departments. Outpatients had moderately severe RSV-associated illness, but few of the illnesses (3%) were diagnosed as being caused by RSV. RSV infection is associated with substantial morbidity in U.S. children in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children will have a limited effect on the total disease burden of RSV infection. 2009 Massachusetts Medical Society
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            Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants

            Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain.
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              Seasonality of Respiratory Syncytial Virus — United States, 2017–2023

              In the United States, respiratory syncytial virus (RSV) infections cause an estimated 58,000–80,000 hospitalizations among children aged 90% of tests reported ( 9 ). Surveillance years were defined based on troughs in RSV circulation. During 2017–2020 (the prepandemic period), surveillance years began in early July (epidemiologic week 27) and ended the following year in late June (week 26). Because the typical winter RSV epidemic was absent during 2020–21, and the 2021–22 epidemic began in the spring, the 2021–22 and 2022–23 surveillance years (pandemic period) were defined as early March (week 9) to late February (week 8) of the following year. § Several methods for characterizing RSV seasonality were explored (Supplementary Table 1, https://stacks.cdc.gov/view/cdc/126381) (Supplementary Table 2, https://stacks.cdc.gov/view/cdc/126380). A 3% test positivity threshold was chosen because it prospectively identified a high proportion of annual RSV detections during epidemic periods of moderate duration. The epidemic onset and offset (or end) weeks were defined, respectively, as the first and last of 2 consecutive weeks when the percentage of PCR tests positive for RSV was ≥3%. The epidemic duration was the inclusive number of weeks between onset and offset. The peak was defined as the week with the highest percentage of PCR tests positive for RSV. Epidemic onset, offset, peak, and duration were identified for each season at the national level and by U.S. Department of Health and Human Services (HHS) region. ¶ Because patterns of weekly RSV circulation in Alaska, Florida, and Hawaii are different from those in other states within their assigned regions (HHS Regions 10, 4, and 9, respectively), these states were excluded from regional analyses. State-level seasonality for Florida is reported; however, an insufficient number of laboratories in Alaska and Hawaii consistently reported PCR data to present state-level seasonality in those states. The analysis included data from laboratories that consistently conducted PCR testing.** This activity was conducted consistent with applicable federal law and CDC policy. †† During the period with weeks ending July 8, 2017–February 25, 2023, five distinct RSV epidemics occurred: three before the COVID-19 pandemic (2017–18, 2018–19, and 2019–20) and two during the pandemic (2021–22 and 2022–23). Using the 3% epidemic threshold, no seasonal RSV epidemic was observed to occur during the 2020–21 surveillance year (Figure 1). The number of tests performed increased substantially during the pandemic (Table). FIGURE 1 Percentage* of polymerase chain reaction test results positive for respiratory syncytial virus, by epidemiologic week — National Respiratory and Enteric Virus Surveillance System, United States, July 2017–February 2023 Abbreviations: PCR = polymerase chain reaction; RSV = respiratory syncytial virus. * Three-week centered moving averages of percentage of RSV-positive PCR test results nationally. The threshold for a seasonal epidemic was set at 3% RSV-positive PCR test results (not based on a moving average). The figure is a line chart showing percentage of polymerase chain reaction test results positive for respiratory syncytial virus in the United States during July 2017–February 2023. TABLE Summary of respiratory syncytial virus seasons, by U.S. Department of Health and Human Services Region* and in Florida — National Respiratory and Enteric Virus Surveillance System, July 2017–February 2023 † HHS region (headquarters) or state, RSV season No. of laboratories reporting No. of tests performed Onset epidemiologic week§ (mo) Peak epidemiologic week¶ (mo) Offset epidemiologic week** (mo) Epidemic duration, no. of wks†† % of annual detections in epidemic period§§ National 2017–18 130 810,977 42 (Oct) 51 (Dec) 16 (Apr) 27 96 2018–19 138 816,512 41 (Oct) 51 (Dec) 16 (Apr) 28 95 2019–20 166 999,493 42 (Oct) 51 (Dec) 12 (Mar) 23 95 2021–22 196 1,849,047 21 (May) 30 (Jul) 1 (Jan) 33 92 2022–23 221 3,160,659 24 (Jun) 44 (Nov) 3 (Jan) 32 92 Region 1 (Boston) 2017–18 9 38,902 44 (Nov) 52 (Dec) 17 (Apr) 26 97 2018–19 10 39,951 45 (Nov) 52 (Dec) 15 (Apr) 23 94 2019–20 12 53,441 44 (Nov) 52 (Dec) 12 (Mar) 21 96 2021–22 11 70,122 25 (Jun) 36 (Sep) 51 (Dec) 27 90 2022–23 10 184,128 35 (Sep) 44 (Nov) 50 (Dec) 16 81 Region 2 (New York City) 2017–18 8 52,010 43 (Oct) 1 (Jan) 13 (Mar) 23 93 2018–19 9 62,066 44 (Nov) 51 (Dec) 13 (Mar) 22 89 2019–20 13 100,384 43 (Oct) 49 (Dec) 10 (Mar) 20 90 2021–22 9 186,986 30 (Jul) 39 (Oct) 50 (Dec) 21 78 2022–23 11 286,733 38 (Sep) 45 (Nov) 51 (Dec) 14 74 Region 3 (Philadelphia) 2017–18 11 55,660 42 (Oct) 52 (Dec) 14 (Apr) 25 94 2018–19 9 46,260 43 (Oct) 49 (Dec) 13 (Mar) 23 93 2019–20 13 63,745 43 (Oct) 1 (Jan) 9 (Feb) 19 90 2021–22 16 85,062 24 (Jun) 34 (Aug) 52 (Jan) 29 92 2022–23 13 142,867 23 (Jun) 42 (Oct) 3 (Jan) 33 95 Region 4 (Atlanta) 2017–18 9 55,316 40 (Oct) 51 (Dec) 14 (Apr) 27 92 2018–19 9 59,747 38 (Sep) 52 (Dec) 13 (Mar) 28 92 2019–20 11 60,429 38 (Sep) 48 (Nov) 9 (Feb) 24 92 2021–22 11 130,818 14 (Apr) 30 (Jul) 47 (Nov) 34 86 2022–23 13 267,547 21 (May) 40 (Oct) 50 (Dec) 30 89 Region 5 (Chicago) 2017–18 33 201,222 44 (Nov) 50 (Dec) 17 (Apr) 26 95 2018–19 35 185,950 41 (Oct) 1 (Jan) 12 (Mar) 24 92 2019–20 51 273,402 42 (Oct) 51 (Dec) 11 (Mar) 22 93 2021–22 68 462,017 24 (Jun) 33 (Aug) 49 (Dec) 26 86 2022–23 81 725,015 32 (Aug) 44 (Nov) 2 (Jan) 23 90 Region 6 (Dallas) 2017–18 16 128,254 40 (Oct) 48 (Dec) 17 (Apr) 30 97 2018–19 16 123,577 40 (Oct) 47 (Nov) 13 (Mar) 26 94 2019–20 17 131,460 40 (Oct) 48 (Nov) 11 (Mar) 24 95 2021–22 22 300,954 20 (May) 28 (Jul) 1 (Jan) 34 96 2022–23 21 355,621 17 (Apr) 41 (Oct) 3 (Jan) 39 95 Region 7 (Kansas City) 2017–18 8 24,443 46 (Nov) 7 (Feb) 20 (May) 27 97 2018–19 9 32,138 46 (Nov) 52 (Dec) 18 (May) 25 97 2019–20 9 36,150 43 (Oct) 51 (Dec) 13 (Mar) 23 97 2021–22 14 120,813 21 (May) 33 (Aug) 51 (Dec) 31 91 2022–23 29 247,426 36 (Sep) 44 (Nov) 2 (Jan) 19 88 Region 8 (Denver) 2017–18 9 55,535 48 (Dec) 7 (Feb) 17 (Apr) 22 96 2018–19 9 57,877 48 (Dec) 5 (Feb) 18 (May) 23 97 2019–20 11 64,399 46 (Nov) 4 (Jan) 14 (Apr) 21 97 2021–22 10 119,298 26 (Jul) 39 (Oct) 1 (Jan) 28 92 2022–23 9 115,584 39 (Oct) 45 (Nov) 5 (Feb) 19 90 Region 9 (San Francisco) 2017–18 11 121,569 47 (Nov) 6 (Feb) 16 (Apr) 22 97 2018–19 8 108,118 48 (Dec) 6 (Feb) 17 (Apr) 22 97 2019–20 8 108,085 47 (Nov) 1 (Jan) 13 (Mar) 19 96 2021–22 9 163,200 29 (Jul) 49 (Dec) 6 (Feb) 30 98 2022–23 9 473,657 37 (Sep) 45 (Nov) 4 (Jan) 20 91 Region 10 (Seattle) 2017–18 8 56,212 47 (Nov) 4 (Jan) 15 (Apr) 21 96 2018–19 15 74,851 47 (Nov) 6 (Feb) 17 (Apr) 23 95 2019–20 13 74,837 46 (Nov) 52 (Dec) 12 (Mar) 19 95 2021–22 18 154,248 34 (Aug) 50 (Dec) 5 (Feb) 24 94 2022–23 20 228,081 39 (Oct) 45 (Nov) 5 (Feb) 19 90 Florida 2017–18 6 20,224 32 (Aug) 46 (Nov) 9 (Mar) 30 87 2018–19 7 24,390 29 (Jul) 45 (Nov) 13 (Mar) 37 91 2019–20 5 28,626 33 (Aug) 48 (Nov) 7 (Feb) 27 88 2021–22 5 43,340 12 (Mar) 23 (Jun) 49 (Dec) 38 90 2022–23 2 68,801 18 (May) 40 (Oct) 3 (Jan) 38 90 Abbreviations: HHS = U.S. Department of Health and Human Services; PCR = polymerase chain reaction; RSV = respiratory syncytial virus. * https://www.hhs.gov/about/agencies/iea/regional-offices/index.html. Patterns of weekly RSV circulation in Alaska, Florida, and Hawaii are distinct from other states within their assigned regions (HHS regions 10, 4, and 9, respectively); therefore, these states were excluded from regional analyses. State-level seasonality for Florida is reported; however, there are an insufficient number of laboratories consistently reporting RSV PCR data to present state-level seasonality in Alaska and Hawaii. † Because the typical seasonal RSV epidemic was notably absent during the 2020–21 surveillance year, data from this surveillance year are not shown. Surveillance years were defined based on troughs in RSV circulation. During 2017–2020, surveillance years began in epidemiologic week 27 (early July) and ended the following year in epidemiologic week 26 (late June). During the COVID-19 pandemic (2021–22 and 2022–23), surveillance years began in epidemiologic week 9 (early March) and ended the following year in epidemiologic week 8 (late February). § The epidemic onset was defined as the first of 2 consecutive weeks when the percentage of PCR tests positive for RSV was ≥3%. ¶ The epidemic peak was defined as the week with the highest percentage of PCR tests positive for RSV. ** The epidemic offset was defined as the last of 2 consecutive weeks when the percentage of PCR tests positive for RSV was ≥3%. †† The epidemic duration was the inclusive number of weeks between onset and offset. §§ Annual percentage of detections in the epidemic period was defined as the proportion of all detections during a surveillance year that occurred during the epidemic period. Nationally, RSV epidemics during the 3 surveillance years preceding the COVID-19 pandemic (2017–2020) began in October, peaked in December, and lasted a median of 27 weeks before the offset during March–April (Table). In contrast, the 2021–22 epidemic began 21 weeks earlier (May), peaked in July, and lasted 33 weeks until January 2022, although the peak percentage of RSV-positive PCR results (15%) was comparable with that during prepandemic seasons (Figure 1). During the 2022–23 surveillance year, onset occurred in June, the proportion of positive PCR results peaked in November, and the peak was higher (19%) than that during prepandemic seasons (range = 13%–16%). The epidemic lasted 32 weeks until the offset occurred in January. In both the prepandemic and pandemic periods, RSV epidemics began earliest in Florida and the Southeast and later in regions further north and west (Figure 2). During the Florida prepandemic seasons, the median onset occurred in August, the peak occurred in November, and the epidemic continued until March (median duration = 30 weeks) (Table) (Supplementary Figure, https://stacks.cdc.gov/view/cdc/126382). In the 10 HHS regions (excluding Alaska, Florida, and Hawaii), the median onset ranged from September in Region 4 to December in Region 8. The median epidemic peaks ranged from November in Region 6 to February in Regions 8 and 9. Median offsets ranged from March in Region 5 to May in Region 7; offsets occurred 2–6 weeks earlier during the 2019–20 surveillance year (i.e., when the COVID-19 pandemic began) compared with the preceding 2 surveillance years. The shortest epidemic periods occurred in Region 10 (median = 21 weeks), and the longest occurred in Region 4 (median = 27 weeks). FIGURE 2 Respiratory syncytial virus epidemic onsets* in U.S. Department of Health and Human Services Regions 1–10† and in Florida — National Respiratory and Enteric Virus Surveillance System, United States, July 2017–February 2023§ Abbreviations: FL = Florida; RSV = respiratory syncytial virus. * The epidemic onset was defined as the first of 2 consecutive weeks of a surveillance year when the percentage of PCR tests positive for RSV was ≥3%. Median epidemic onset weeks were calculated for the three RSV epidemics that occurred before the COVID-19 pandemic (2017–18, 2018–19, and 2019–20). † https://www.hhs.gov/about/agencies/iea/regional-offices/index.html. Patterns of weekly RSV circulation in Alaska, Florida, and Hawaii are distinct from other states within their assigned regions; therefore, these states were excluded from regional analyses. State-level seasonality for Florida is reported; however, there are an insufficient number of laboratories consistently reporting polymerase chain reaction testing data to present state-level seasonality in Alaska and Hawaii. § Surveillance years were defined based on troughs in RSV circulation. During 2017–2020, surveillance years began in epidemiologic week 27 (early July) and ended the following year in epidemiologic week 26 (late June). The aberrant 2020–21 surveillance year was defined as week 27 through week 8 (late February) inclusive. During the COVID-19 pandemic (2021–22 and 2022–23), surveillance years began in epidemiologic week 9 (early March) and ended the following year in epidemiologic week 8. The figure is a set of three maps showing respiratory syncytial virus epidemic onsets, by U.S. Department of Health and Human Services Regions 1–10 and in Florida, in the United States, during July 2017–February 2023 according to the National Respiratory and Enteric Virus Surveillance System. During the 2021–22 (pandemic) surveillance year, epidemic onsets across the 10 HHS regions and Florida occurred a median of 20 weeks earlier (range = 13–25 weeks) than the median onsets during the prepandemic period (range = March [Florida] to August [Region 10]). Epidemic peaks also occurred earlier than they did during the prepandemic years, ranging from July in Region 6 to December in Region 10. Offsets ranged from November (Region 4) to February (Region 9), which is when prepandemic peaks typically occurred. During the 2021–22 surveillance year, the epidemic durations were a median of 6 weeks longer than the median durations of prepandemic RSV epidemics (range = 21 weeks [Region 2] to 38 weeks [Florida]). During the 2022–23 season, early epidemic onsets (April–June) were observed in Florida and HHS Regions 3, 4, and 6, but the percentage of RSV-positive PCR test results levelled off before increasing again in September (Figure 1) (Table). In other regions, epidemics began between August and October. Seasons peaked from October in Region 4 to November in regions further north and west (Regions 2, 8, 9, and 10). Epidemics ended between December and February. Discussion In the United States, disruption of the seasonal circulation of RSV was observed during the COVID-19 pandemic as nonpharmaceutical interventions (e.g., school closures and masking) reduced respiratory virus transmission and led to an accumulation of susceptible persons resulting in large epidemics with atypical seasonality ( 10 ). After the implementation of nonpharmaceutical interventions in March 2020, the 2019–20 RSV epidemic ended earlier than the previous two epidemics. During 2020, RSV circulated at historically low levels. In 2021, RSV circulation began earlier (in late spring), when nonpharmaceutical interventions eased, and continued longer than it did during prepandemic years, although the percentage of RSV-positive PCR tests at the peak was comparable to those during prepandemic years. The 2022–23 epidemic began later than the 2021–22 epidemic but earlier than prepandemic epidemics, suggesting a reversion toward prepandemic seasonality with winter peaks. The peak percentage of positive RSV test results was higher than those in previous years, suggesting higher intensity of circulation. Across both prepandemic and pandemic years, RSV circulation began in Florida and the Southeast and later in regions to the north and west. The consistency of this pattern could help predict the timing of future epidemics in specific regions. The findings in this report are subject to at least four limitations. First, reporting to NREVSS is voluntary, and analysis is limited to laboratories that consistently report, which might not represent local and state circulation. Second, differences in testing across regions and changes in testing practices and diagnostics over time, including increased panel testing during the COVID-19 pandemic, could have affected the baseline percentage of positive test results and trends, and thus the onset, offset, and duration of epidemics. Third, there is no standard method for characterizing seasonality; seasonal attributes vary depending on the method used. An earlier description of RSV seasonality in the United States used a more sensitive method (retrospective slope 10 §§ ) that can only be applied retrospectively and results in longer epidemic durations ( 6 , 9 ). However, the 3% RSV-positive PCR threshold used in the current analysis can be applied in near real time and identified epidemic periods that included a high concentration of detections ( 9 ). Finally, this analysis describes regional and national trends; locally available data and region-specific thresholds might better reflect circulation patterns within specific jurisdictions. Although the peak in RSV circulation during November 2022 suggests that seasonal patterns are returning to those observed in prepandemic years, it is uncertain whether this reversion will continue in the upcoming surveillance year. To monitor RSV circulation, CDC has conducted year-round surveillance using a variety of approaches including active, population-based surveillance for RSV-associated hospitalizations and outpatient visits. ¶¶ Clinicians should be aware that atypical RSV epidemics might continue and consider testing patients for multiple respiratory pathogens when indicated. With new prevention products nearing licensure, including vaccines for older adults, maternal vaccines, and long-acting RSV immunoprophylaxis for infants and children, policy makers should consider RSV seasonality when making recommendations about the timing of studies and administration of new immunization and other RSV prevention products. Summary What is already known about this topic? In the United States, the timing of seasonal respiratory syncytial virus (RSV) epidemics (October–April) was disrupted during the COVID-19 pandemic. What is added by this report? RSV circulation was historically low during 2020–21 and began earlier and continued longer during 2021–22 than during prepandemic seasons. The 2022–23 season started later than the 2021–22 season but earlier than prepandemic seasons, suggesting a return toward prepandemic seasonality. What are the implications for public health practice? Ongoing monitoring of RSV seasonality can guide the timing of immunoprophylaxis and evaluation of new immunization products. Although an eventual return to prepandemic RSV seasonality is expected, clinicians should be aware that off-season RSV circulation might continue.
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                Author and article information

                Contributors
                Journal
                MMWR Morb Mortal Wkly Rep
                MMWR Morb Mortal Wkly Rep
                WR
                Morbidity and Mortality Weekly Report
                Centers for Disease Control and Prevention
                0149-2195
                1545-861X
                07 March 2024
                07 March 2024
                : 73
                : 9
                : 209-214
                Affiliations
                Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC; UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Texas Children’s Hospital, Houston, Texas; Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Pediatrics, University of Rochester Medical Center and University of Rochester–Golisano Children’s Hospital, Rochester, New York; Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, Missouri; Department of Pediatrics Children’s Mercy Hospital, Kansas City, Missouri.
                Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC
                Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC
                Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC
                Department of Pediatrics, Vanderbilt University Medical Center
                Department of Pediatrics, Vanderbilt University Medical Center
                Department of Pediatrics, Seattle Children’s Hospital
                Department of Pediatrics, Seattle Children’s Hospital
                Baylor College of Medicine
                Texas Children’s Hospital and Baylor College of Medicine
                Department of Pediatrics, University of Rochester Medical Center and University of Rochester–Golisano Children’s Hospital
                Department of Pathology and Laboratory Medicine, Children’s Mercy Kansas City
                Department of Pathology and Laboratory Medicine, Children’s Mercy Kansas City
                Department of Pediatrics, University of Pittsburgh School of Medicine
                Department of Pediatrics, University of Pittsburgh School of Medicine
                Author notes
                Corresponding author: Heidi L. Moline, ick6@ 123456cdc.gov .
                Article
                mm7309a4
                10.15585/mmwr.mm7309a4
                10932582
                38457312
                9d2d8174-3fe4-4f70-9fb0-587c0bebc841

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