Changes in the global hospitalisation burden of respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis.

BACKGROUND: The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective. METHODS: We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019. FINDINGS: We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed. INTERPRETATION: The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries. FUNDING: EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO.

Biological factors that may impair transplacental transfer of RSV antibodies: Implications for maternal immunization policy and research priorities for low- and middle-income countries.

Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infection (ALRI), including bronchiolitis and pneumonia, in infants and children worldwide. Protection against RSV is primarily antibody mediated and passively acquired RSV neutralizing antibody can protect infants from RSV ALRI. Maternal immunization is an attractive strategy for the prevention of RSV in early infancy when immune responses to active immunization may be suboptimal and most severe RSV disease and death occur. However, several biologic factors have been shown to potentially attenuate or interfere with the transfer of protective naturally acquired antibodies from mother to fetus and could therefore also reduce vaccine effectiveness through impairment of transfer of vaccine-induced antibodies. Many of these factors are prevalent in low- and middle-income countries (LMIC) which experience the greatest burden of RSV-associated mortality; more data are needed to understand these mechanisms in the context of RSV maternal immunization. This review will focus on what is currently known about biologic conditions that may impair RSV antibody transfer, including preterm delivery, low birthweight, maternal HIV infection, placental malaria, and hypergammaglobulinemia (high levels of maternal total IgG). Key data gaps and priority areas for research are highlighted and include improved understanding of the epidemiology of hypergammaglobulinemia and the mechanisms by which it may impair antibody transfer. Key considerations for ensuring optimal vaccine effectiveness in LMICs are also discussed.