Abstract
Background
In China, respiratory syncytial virus (RSV) infections traditionally occur during the spring and winter seasons. However, a shift in the seasonal trend was noted in 2020–2022, during the coronavirus disease 2019 (COVID-19) pandemic.
Methods
This study investigated the seasonal characteristics of RSV infection in children hospitalized with acute lower respiratory tract infections (ALRTIs). The RSV epidemic season was defined as RSV positivity in > 10% of the hospitalized ALRTI cases each week. Nine RSV seasons were identified between 2013 and 2022, and nonlinear ordinary least squares regression models were used to assess the differences in year-to-year epidemic seasonality trends.
Results
We enrolled 49,658 hospitalized children diagnosed with ALRTIs over a 9-year period, and the RSV antigen-positive rate was 15.2% (n = 7,566/49,658). Between 2013 and 2022, the average onset and end of the RSV season occurred in week 44 (late October) and week 17 of the following year, respectively, with a typical duration of 27 weeks. However, at the onset of the COVID-19 pandemic, the usual spring RSV peak did not occur. Instead, the 2020 epidemic started in week 32, and RSV seasonality persisted into 2021, lasting for an unprecedented 87 weeks before concluding in March 2022.
Conclusions
RSV seasonality was disrupted during the COVID-19 pandemic, and the season exhibited an unusually prolonged duration. These findings may provide valuable insights for clinical practice and public health considerations.
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Background
Globally, respiratory syncytial virus (RSV) is a prevalent cause of acute lower respiratory tract infections (ALRTIs) in childhood, and contributes significantly to hospital admissions among young children. This places a substantial burden on healthcare services. Nearly half of the worldwide disease burden associated with RSV occurs in just five countries: Pakistan, India, Nigeria, Indonesia, and China. In China, the estimated annual hospitalizations for infants and young children due to RSV infection range from 215,000 to 500,000 [1].
RSV activity exhibits a seasonal pattern in most regions, and its seasonal epidemics are a leading cause of hospitalization and mortality globally, particularly due to bronchiolitis and pneumonia [2, 3]. The RSV season is typically characterized by an RSV rate exceeding the defined threshold for a specific duration. RSV infection incidence peaks during winter and spring in temperate regions and during rainy seasons in tropical regions. The RSV season commences between March and June in countries in the Southern hemisphere and between September and December in the Northern hemisphere [4]. A study reported the long-term time-series data of medically attended first-time RSV infection among young children. From 2010 to 2019, the monthly incidence rate of medically attended RSV infection in children aged 0–5 years of the United States followed a consistent seasonal pattern: rising from September to November, peaking from December to January, then drop** from February to April, with sustained low rate during May to August [5]. Another study found that states with colder, drier weather and a large seasonal swing in potential evapotranspiration tended to experience an alternating pattern of ‘‘early-big’’ RSV epidemics one year followed by a ‘‘late-small’’ epidemic the next year [6]. In China, the incidence of RSV infection typically peaks between November and February of the following year [7].
Several RSV vaccine candidates and monoclonal antibodies are currently in the advanced clinical development stage [8]. Therefore, prevention of RSV transmission remains a promising strategy to control seasonal epidemics. Prior to the COVID-19 pandemic, RSV epidemiology adhered to a seasonal pattern worldwide [3]. Interestingly, the COVID-19 pandemic has significantly influenced RSV epidemiology, with many countries experiencing an absence of RSV infections during the first pandemic winter [9]. A delayed summer epidemic was observed in various locations worldwide [10,11,12]. The success in preventing RSV infections was attributed to the strict implementation of non-pharmacological public health interventions targeting COVID-19. Concerns have been raised regarding potential severe RSV epidemics in the future due to “immunity debt,” a term that describes reduced protective immunity resulting from prolonged periods of low exposure to a pathogen, rendering a greater proportion of the population susceptible to the disease [13, 14].
China bears a significant burden of RSV infection [15], but few studies have assessed the seasonality or trends of RSV infections. Furthermore, during the COVID-19 outbreak, limited availability of epidemiological surveillance data for other respiratory viruses could have impeded the implementation of therapy and prophylactic interventions for RSV. The present study retrospectively examined available surveillance data for RSV in children hospitalized with ALRTI in Hunan, China, between 2013 and 2022. It evaluated seasonal changes in RSV infections both before and after the COVID-19 pandemic.
Methods
Population and methods
This retrospective study spanned a 9-year period from July 1, 2013, to June 30, 2022. All children hospitalized with ALRTI were included in the RSV epidemiological surveillance program conducted at the Children’s Medical Center of Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University). Samples were collected after obtaining informed consent from the parents or guardians of each child, and the research protocol received approval from the hospital’s ethics review committee.
The collected data included the date of hospital admission, demographic information, disease severity, length of hospital stay, and the cost of stay in pediatric wards. Recorded complications included congenital heart disease, malnutrition, premature birth, chronic lung disease, anemia, and asthma. We collected China’s GDP per habitant in the study period to compare the cost with an average outcome (2013, US $7020; 2014, US $7636; 2015, US $8016; 2016, US $8094; 2017, US $8817; 2018, US $9905; 2019, US $10,143; 2020, US $10,408; 2021, US $12,617; and 2022, US $12,720, respectively).
Experimental process
Nasopharyngeal swabs were obtained within 24 h of hospitalization for virological diagnosis. Nasopharyngeal aspirate specimens of the enrolled children were collected by trained nurses after admission and were transported immediately to the clinical laboratory center. Seven common pathogens included respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A (Flu A), influenza virus B (Flu B), and parainfluenza virus types 1–3 (PIV1–3). For the DFA, the cell pellets from the NPS samples were suspended in several drops of sterile phosphate-buffered saline, and the resulting cell suspension was spotted onto an acetone-cleaned slide. An anti-RSV monoclonal antibody labeled with fluorescein isothiocyanate from the D3 UltraTM DFA Respiratory Virus Screening & ID Kit (Diagnostic Hybrids Inc., Athens, OH, USA) was used for RSV identification using the DFA and was conducted by professional staff following standard operating procedures.
Definitions
The “monitoring year” was defined as July 1 (week 27) to June 30 of the subsequent year. All enrolled hospitalized patients were 14 years of age or younger, admitted for ALRTI, and diagnosed based on clinical and radiologic findings. Eligible children exhibited an illness characterized by an acute or worsened cough as the primary or dominant symptom, or lower respiratory tract infection symptoms lasting less than 28 days. Exclusion criteria were children with immunosuppression related to solid organ or hematopoietic stem cell transplantation, chemotherapy, tumors, hematological diseases, a history of HIV, steroid treatment for more than 30 days, or immunosuppressant treatment.
RSV positivity rate was defined as the number of positive RSV specimens divided by the total number of specimens, multiplied by 100. Seasons were categorized as winter (weeks 49 to 9 of the following year), spring (weeks 10–22), summer (weeks 23–35), and autumn (weeks 36–48). Five age groups were defined: 28 days to 5 months, 6–11 months, 12–23 months, 24–59 months, and ≥ 60 months.
The RSV season was defined as consecutive weeks during which the percentage of RSV testing positive per week exceeded a 10% threshold [ We enrolled 49,658 hospitalized children diagnosed with ALRTIs over a 9-year period, spanning both before and during the COVID-19 epidemic, to assess RSV prevalence. COVID-19 has influenced the transmission pattern of RSV since 2020, and the patients in our study exhibited distinct demographic and clinical changes in the context of COVID-19. RSV seasonality was disrupted during the COVID-19 pandemic, and the season exhibited an unusually prolonged duration. Despite these observations, RSV still warrants great attention to prevent unusual rebounds and unexpected impacts. In addition to future investigations and the development of passive and active immunization, thorough surveillance of RSV variation remains crucial as we transition into the post-COVID-19 era.Conclusions
Data availability
The datasets of the current study are available from the corresponding author on reasonable request.
Change history
20 March 2024
A Correction to this paper has been published: https://doi.org/10.1186/s12985-024-02340-y
Abbreviations
- RSV:
-
Respiratory syncytial virus
- ALRTIs:
-
Acute lower respiratory tract infections
- COVID-19:
-
The coronavirus disease 2019
- NPIs:
-
Non-pharmaceutical interventions
- IQR:
-
Interquartile ranges
- SARS-CoV-2:
-
Severe acute respiratory syndrome coronavirus 2
References
Shi T, McAllister DA, O’Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017;390(10098):946–58.
Pneumonia Etiology Research for Child Health (PERCH) Study Group. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet. 2019;394(10200):757–79.
Li Y, Reeves RM, Wang X, Bassat Q, Brooks WA, Cohen C, et al. Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis. Lancet Glob Health. 2019;7(8):e1031–45.
Chadha M, Hirve S, Bancej C, Barr I, Baumeister E, Caetano B, et al. Human respiratory syncytial virus and influenza seasonality patterns-early findings from the WHO global respiratory syncytial virus surveillance. Influenza Other Respir Viruses. 2020;14(6):638–46.
Wang L, Berger N, Davis PB, Kaelber DC, Volkow N, Xu R. Time trend and seasonality in medically attended respiratory syncytial virus (RSV) infections in US children aged 0–5 years, January 2010-January 2023. Fam Med Community Health. 2023;11(4):e002453. https://doi.org/10.1136/fmch-2023-002453. PMID: 37844966; PMCID: PMC10582996.
Pitzer VE, Viboud C, Alonso WJ, Wilcox T, Metcalf CJ, Steiner CA, et al. Environmental drivers of the spatiotemporal dynamics of respiratory syncytial virus in the United States. PLoS Pathog. 2015;11(1):e1004591. https://doi.org/10.1371/journal.ppat.1004591. PMID: 25569275; PMCID: PMC4287610.
Yu J, Liu C, **ao Y, **ang Z, Zhou H, Chen L, et al. Respiratory Syncytial Virus Seasonality, Bei**g, China, 2007–2015. Emerg Infect Dis. 2019;25(6):1127–35.
Li Y, Hodgson D, Wang X, Atkins KE, Feikin DR, Nair H. Respiratory syncytial virus seasonality and prevention strategy planning for passive immunisation of infants in low-income and middle-income countries: a modelling study. Lancet Infect Dis. 2021;21(9):1303–12.
Bardsley M, Morbey RA, Hughes HE, Beck CR, Watson CH, Zhao H, et al. Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study. Lancet Infect Dis. 2023;23(1):56–66.
Foley DA, Yeoh DK, Minney-Smith CA, Martin AC, Mace AO, Sikazwe CT, et al. The Interseasonal resurgence of respiratory Syncytial Virus in Australian Children following the Reduction of Coronavirus Disease 2019-Related Public Health Measures. Clin Infect Dis. 2021;73(9):e2829–30.
Delestrain C, Danis K, Hau I, Behillil S, Billard MN, Krajten L, et al. Impact of COVID-19 social distancing on viral infection in France: a delayed outbreak of RSV. Pediatr Pulmonol. 2021;56(12):3669–73.
Foley DA, Phuong LK, Peplinski J, Lim SM, Lee WH, Farhat A, et al. Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia. Arch Dis Child. 2022;107(3):e7.
Hatter L, Eathorne A, Hills T, Bruce P, Beasley R. Respiratory syncytial virus: paying the immunity debt with interest. Lancet Child Adolesc Health. 2021;5(12):e44–5.
Billard MN, Bont LJ. Quantifying the RSV immunity debt following COVID-19: a public health matter. Lancet Infect Dis. 2023;23(1):3–5.
Ren L, Cui L, Wang Q, Gao L, Xu M, Wang M, et al. Cost and health-related quality of life for children hospitalized with respiratory syncytial virus in Central China. Influenza Other Respir Viruses. 2023;17(8):e13180.
Midgley CM, Haynes AK, Baumgardner JL, Chommanard C, Demas SW, Prill MM, et al. Determining the seasonality of respiratory Syncytial Virus in the United States: the impact of increased Molecular Testing. J Infect Dis. 2017;216(3):345–55.
Haynes AK, Prill MM, Iwane MK, Gerber SI. Centers for Disease Control and Prevention (CDC). Respiratory syncytial virus–United States, July 2012-June 2014. MMWR Morb Mortal Wkly Rep. 2014;63(48):1133–6.
Grilc E, Prosenc Trilar K, Lajovic J, Sočan M. Determining the seasonality of respiratory syncytial virus in Slovenia. Influenza Other Respir Viruses. 2021;15(1):56–63. https://doi.org/10.1111/irv.12779. Epub 2020 Jul 12. PMID: 32656961; PMCID: PMC7767947.
Stolwijk AM, Straatman H, Zielhuis GA. Studying seasonality by using sine and cosine functions in regression analysis. J Epidemiol Community Health. 1999;53(4):235–8.
Obando-Pacheco P, Justicia-Grande AJ, Rivero-Calle I, Rodríguez-Tenreiro C, Sly P, Ramilo O, et al. Respiratory Syncytial Virus Seasonality: A Global Overview. J Infect Dis. 2018;217(9):1356–64.
Hamid S, Winn A, Parikh R, Jones JM, McMorrow M, Prill MM, et al. Seasonality of respiratory Syncytial Virus - United States, 2017–2023. MMWR Morb Mortal Wkly Rep. 2023;72(14):355–61.
Deng S, Guo L, Cohen C, Meijer A, Moyes J, Pasittungkul S et al. Impact of subgroup distribution on seasonality of human respiratory syncytial virus: a global systematic analysis. J Infect Dis 2023 May 30:jiad192.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33.
Gomez GB, Mahé C, Chaves SS. Uncertain effects of the pandemic on respiratory viruses. Science. 2021;372(6546):1043–4.
Huang QS, Wood T, Jelley L, Jennings T, Jefferies S, Daniells K, et al. Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand. Nat Commun. 2021;12(1):1001.
Redlberger-Fritz M, Kundi M, Aberle SW, Puchhammer-Stöckl E. Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections in Austria. J Clin Virol. 2021;137:104795.
Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci U S A. 2019;116(52):27142–50.
Weinberger Opek M, Yeshayahu Y, Glatman-Freedman A, Kaufman Z, Sorek N, Brosh-Nissimov T. Delayed respiratory syncytial virus epidemic in children after relaxation of COVID-19 physical distancing measures, Ashdod, Israel, 2021. Euro Surveill. 2021;26(29):2100706.
Li Y, Wang X, Msosa T, de Wit F, Murdock J, Nair H. The impact of the 2009 influenza pandemic on the seasonality of human respiratory syncytial virus: a systematic analysis. Influenza Other Respir Viruses. 2021;15(6):804–12.
Mak GC, Wong AH, Ho WY, Lim W. The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009–2011. Influenza Other Respir Viruses. 2012;6(3):e6–10. https://doi.org/10.1111/j.1750-2659.2011.00323.x. Epub 2012 Jan 2. PMID: 22212717; PMCID: PMC5657134.
Zheng Z, Pitzer VE, Shapiro ED, Bont LJ, Weinberger DM. Estimation of the timing and intensity of reemergence of respiratory Syncytial Virus following the COVID-19 pandemic in the US. JAMA Netw Open. 2021;4(12):e2141779.
Madaniyazi L, Seposo X, Ng CFS, Tobias A, Toizumi M, Moriuchi H, et al. Respiratory Syncytial Virus outbreaks are predicted after the COVID-19 pandemic in Tokyo, Japan. Jpn J Infect Dis. 2022;75(2):209–11.
Ujiie M, Tsuzuki S, Nakamoto T, Iwamoto N. Resurgence of respiratory Syncytial Virus infections during COVID-19 pandemic, Tokyo, Japan. Emerg Infect Dis. 2021;27(11):2969–70.
Jia R, Lu L, Su L, Lin Z, Gao D, Lv H, et al. Resurgence of respiratory syncytial virus infection during COVID-19 pandemic among children in Shanghai, China. Front Microbiol. 2022;13:938372.
Jiang ML, Xu YP, Wu H, Zhu RN, Sun Y, Chen DM, et al. Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Bei**g, China. J Med Virol. 2023;95(1):e28411.
Li Y, Wang X, Cong B, Deng S, Feikin DR, Nair H. Understanding the potential drivers for respiratory Syncytial Virus Rebound during the Coronavirus Disease 2019 Pandemic. J Infect Dis. 2022;225(6):957–64.
Lambert L, Sagfors AM, Openshaw PJ, Culley FJ. Immunity to RSV in early-life. Front Immunol. 2014;5:466.
Pruccoli G, Castagno E, Raffaldi I, Denina M, Barisone E, Baroero L, et al. The importance of RSV Epidemiological Surveillance: a Multicenter Observational study of RSV infection during the COVID-19 pandemic. Viruses. 2023;15(2):280.
Agha R, Avner JR. Delayed seasonal RSV surge observed during the COVID-19 pandemic. Pediatrics. 2021;148(3):e2021052089.
Acknowledgements
All authors wish to thank the infants and their parents in this study.
Funding
This work was supported by Hunan Provincial Medicine and Health Research Program (Grant No. C202306016954) and Hunan Provincial Key Laboratory of Pediatric Respirology (Grant No. 2019TP1043).
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SZ and TY were responsible for the study concept and design. XH, TW and LY collected study samples and acquired the data. LX, SZ, LZ, and BZ analyzed and interpreted the data. LX, TW SZ and TY have drafted the manuscript and critically revised it for important intellectual content. All authors reviewed the manuscript and approved the final manuscript.
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The study was approved by the Ethics Committee of Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University).
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The authors declare no competing interests.
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The original online version of this article was revised: Following publication of the original article, we have been notified that Figure 5 was a duplicate of Figure 6. Figure 5 has now been replaced with the correct version.
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**e, LY., Wang, T., Yu, T. et al. Seasonality of respiratory syncytial virus infection in children hospitalized with acute lower respiratory tract infections in Hunan, China, 2013–2022. Virol J 21, 62 (2024). https://doi.org/10.1186/s12985-024-02336-8
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DOI: https://doi.org/10.1186/s12985-024-02336-8