Antibody Responses to Respiratory Syncytial Virus: A Cross-Sectional Serosurveillance Study in the Dutch Population Focusing on Infants Younger Than 2 Years

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Abstract

Background

Respiratory syncytial virus (RSV) generally causes mild disease but can cause severe infections in (premature) infants and elderly adults. Here, we studied RSV-specific antibody concentrations throughout life with emphasis on infants and chronic obstructive pulmonary disease (COPD) patients.

Methods

Sera (N = 2655) from 2 nationwide cross-sectional studies in the Netherlands including individuals aged 0–90 years were analyzed for IgG and IgA antibodies to RSV prefusion F, postfusion F, N, Ga, and Gb proteins and for antibody avidity in 42 COPD patients.

Results

Maternal IgG concentrations declined to age 10–12 months. After the first year of life, approximately 40% of children lacked infection-induced IgA antibodies and may therefore be uninfected. All Dutch children showed serological evidence of RSV infection by age 3 years. Antibody concentrations reached a plateau by age 5–9 years and remains constant throughout life. COPD patients had similar levels and avidity of RSV-specific IgG antibodies compared with age-matched healthy controls.

Conclusions

RSV-IgG antibody patterns throughout life can be used to estimate the degree of immunity acquisition to RSV and to identify groups at increased risk of infection. Seroprevalence of IgA could be a proxy to determine RSV infection in children younger than 1 year.

Abstract

RSV-IgG antibody patterns throughout life can be used to estimate the degree of immunity to RSV and identify groups at increased risk of infection while IgA seroprevalence could be used as proxy for RSV infection in children < 1 year.

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Most cited references 34

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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

Ting Shi, David McAllister, Katherine L O'Brien … (2017)

Summary Background We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. Funding The Bill & Melinda Gates Foundation.

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Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Harish Nair, D Nokes, Bradford Gessner … (2010)

Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.

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The burden of respiratory syncytial virus infection in young children.

Caroline Hall, Geoffrey A Weinberg, Marika K. Iwane … (2009)

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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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J Infect Dis

Journal ID (publisher-id): jid

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press (US )

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date Collection: 15 July 2021

Publication date (Electronic): 23 September 2020

Publication date PMC-release: 23 September 2020

Volume: 224

Issue: 2

Pages: 269-278

Affiliations

Center for Infectious Disease control, National Institute of Public Health and the Environment , Bilthoven, the Netherlands

Author notes

Correspondence: Guy Berbers, PhD, RIVM, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, the Netherlands ( guy.berbers@ 123456rivm.nl ).

Author information

Gerco den Hartog https://orcid.org/0000-0002-2103-6315

Article

Publisher ID: jiaa483

DOI: 10.1093/infdis/jiaa483

PMC ID: 8280491

PubMed ID: 32964923

SO-VID: fc727ca0-82d9-4996-8279-028ffc16aa3d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 25 March 2020

Date: 27 July 2020

Date accepted : 17 August 2020

Date: 23 September 2020

Page count

Pages: 10

Funding

Funded by: National Institute of Public Health and the Environment;

Funded by: Dutch Ministry of Health, Welfare and Sport, DOI 10.13039/501100002999;

Award ID: 116019

Funded by: European Union, DOI 10.13039/501100000780;

Funded by: European Federation of Pharmaceutical Industries and Associations, DOI 10.13039/100013322;

Antibody Responses to Respiratory Syncytial Virus: A Cross-Sectional Serosurveillance Study in the Dutch Population Focusing on Infants Younger Than 2 Years

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European Respiratory Society: COVID-19

Most cited references 34

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

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

The burden of respiratory syncytial virus infection in young children.

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