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 [

Conclusions

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.