A surge in human metapneumovirus paediatric respiratory admissions in Western Australia following the reduction of SARS-CoV-2 non-pharmaceutical interventions.

AIM: Western Australian laboratory data demonstrated a decrease in human metapneumovirus (hMPV) detections through 2020 associated with SARS-CoV-2-related non-pharmaceutical interventions (NPIs), followed by a subsequent surge in metropolitan region in mid-2021. We aimed to assess the impact of the surge in hMPV on paediatric hospital admissions and the contribution of changes in testing. METHODS: All respiratory-coded admissions of children aged <16 years at a tertiary paediatric centre between 2017 and 2021 were matched with respiratory virus testing data. Patients were grouped by age at presentation and by ICD-10 AM codes into bronchiolitis, other acute lower respiratory infection (OALRI), wheeze and upper respiratory tract infection (URTI). For analysis, 2017-2019 was utilised as a baseline period. RESULTS: hMPV-positive admissions in 2021 were more than 2.8 times baseline. The largest increase in incidence was observed in the 1-4 years group (incidence rate ratio (IRR) 3.8; 95% confidence interval (CI): 2.5-5.9) and in OALRI clinical phenotype (IRR 2.8; 95% CI: 1.8-4.2). The proportion of respiratory-coded admissions tested for hMPV in 2021 doubled (32-66.2%, P < 0.001), with the greatest increase in wheeze (12-75% in 2021, P < 0.001). hMPV test percentage positivity in 2021 was higher than in the baseline period (7.6% vs. 10.1% in 2021, P = 0.004). CONCLUSION: The absence and subsequent surge underline the susceptibility of hMPV to NPIs. Increased hMPV-positive admissions in 2021 can be partially attributable to testing, but test-positivity remained high, consistent with a genuine increase. Continued comprehensive testing will help ascertain true burden of hMPV respiratory diseases.

An Unusual Resurgence of Human Metapneumovirus in Western Australia Following the Reduction of Non-Pharmaceutical Interventions to Prevent SARS-CoV-2 Transmission.

Non-pharmaceutical interventions (NPIs) to reduce SARS-CoV-2 transmission disrupted respiratory virus seasonality. We examined the unusual return of human metapneumovirus (hMPV) in Western Australia following a period of absence in 2020. We analysed hMPV laboratory testing data from 1 January 2017 to 31 December 2021. Whole-genome sequencing of selected hMPV-positive samples was performed using a tiled-amplicon approach. Following an absence in spring 2020, an unusual hMPV surge was observed during the wet summer season in the tropical Northern region in late 2020. Following a six-month delay, an intense winter season occurred in the subtropical/temperate Southern and Metropolitan regions. Compared to 2017-2019, hMPV incidence in 2021 increased by 3-fold, with a greater than 4-fold increase in children aged 1-4 years. There was a collapse in hMPV diversity in 2020, with the emergence of a single subtype. NPIs contributed to an absent 2020 season and a clonal hMPV resurgence. The summer surge and delayed winter season suggest that prevailing temperature and humidity are keys determinant of hMPV transmission. The increased incidence in 2021 was linked to an expanded cohort of hMPV-naïve 1-4-year-old children and waning population immunity. Further intense and unusual respiratory virus seasons are expected as COVID-19 associated NPIs are removed.

Prevalence of respiratory viruses in community-acquired pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: Respiratory viruses are increasingly detected in children with community-acquired pneumonia but prevalence estimates vary substantially. We aimed to systematically review and pool estimates for 22 viruses commonly associated with community-acquired pneumonia. METHODS: We conducted a systematic review and meta-analysis to determine the prevalence of each of the common respiratory viruses detected by any diagnostic method in children aged up to 18 years with community-acquired pneumonia. We searched MEDLINE, PubMed, Embase, Web of Science, and Scopus databases with no language restrictions for relevant published articles and reports published between Jan 1, 1995, and Dec 31, 2019, restricting the review to pre-COVID-19 pandemic years. Three independent reviewers screened articles and extracted data using a predefined protocol. We calculated the pooled prevalence for each virus in childhood pneumonia using DerSimonian-Laird random-effects models. We assessed bias using the Newcastle-Ottawa Scale. The review protocol was registered in PROSPERO (CRD42016034047). FINDINGS: We identified 186 eligible articles that represented 152 209 children up to age 18 years with community-acquired pneumonia. One or more respiratory viruses were detected in 55·0% (95% CI 50·4-59·7) of paediatric patients with a diagnosis of community-acquired pneumonia; heterogeneity was high (I2=99·4%). Respiratory syncytial virus (22·7%, 20·9-24·5) and rhinovirus (22·1%, 19·5-24·7) were the most commonly detected causes of paediatric pneumonia globally, with other viruses detected in 1-9% of cases. There was non-significant variation in prevalence by the country's national income, under-5 mortality rate, or WHO region. INTERPRETATION: Respiratory viruses are frequently detected in community-acquired pneumonia among children of all ages and geographical regions, with non-significant variation by country's national income or region. Further strategies to limit antibiotic use in children with viral pneumonia and develop treatment and prevention approaches targeting common respiratory viruses are expected to have a substantial effect on the residual burden of childhood pneumonia. FUNDING: None.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Interrupted time-series analysis showed unintended consequences of non-pharmaceutical interventions on pediatric hospital admissions.

OBJECTIVE: COVID-19-associated non-pharmaceutical interventions (NPI) have disrupted respiratory viral transmission. We quantified the changes in pediatric hospital admissions in 2020 from five different NPI phases in Western Australia for acute lower respiratory infections (ALRI) in children in the context of all-cause admissions. STUDY DESIGN AND SETTING: We assessed anonymised hospitalization data from Perth Children's Hospital (Jan 2015-Dec 2020) for all-cause admissions, ALRI, febrile illnesses and trauma (negative control) in those <17 years. We evaluated absolute changes in admissions and the weekly change estimated from interrupted time-series models. RESULTS: The absolute number of admissions was comparable in 2020 (15,678) vs. 2015 to 2019 average (15,310). Following the introduction of strict NPIs, all-cause admissions declined by 35%, recovered to pre-pandemic levels, then increased by 24% following NPI cessation. ALRI admissions in children <5 years initially declined by 89%, which was sustained throughout the gradual easing of NPI until an increase of 579% (997% in <3 months) following the final easing of NPI. Admissions for trauma showed minimal changes in 2020 compared to preceding years. CONCLUSION: COVID-19-associated NPI had significant unintended consequences in health service utilization, especially for ALRI and infants <3 months, prompting the need to understand viral transmission dynamics in young children.

Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia.

BACKGROUND: Following a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020. METHOD: At a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020. RESULTS: RSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity. INTERPRETATION: The 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naïve children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.

Impact of Coronavirus Disease 2019 Public Health Measures on Detections of Influenza and Respiratory Syncytial Virus in Children During the 2020 Australian Winter.

Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.