Respiratory viruses in infancy and rapid RSV diagnostics

Abstract

In this thesis I have described the use of different point-of-care tests (POCTs) on respiratory syncytial virus (RSV) as well as the burden and dynamics of respiratory viruses in infants. In part one of the thesis I described the use of different POCTs on RSV in infants and in older adults. Our studies were performed within our prospective international RESCEU birth cohort and older adult cohort in which the primary objective was to determine the burden of RSV. In Chapter 2 the performance of rapid antigen detection test BinaxNOW® RSV (BN) was evaluated. Low sensitivity was found of rapid antigen test BN for RSV detection in infants, with a sensitivity of 7.6% (95% CI 3.3-16.5%), specificity was 100% (95% CI 96.2-100%). The performance of a molecular rapid detection test in older adults was assessed in Chapter 3. The performance of Xpert® Xpress Flu/RSV compared to routine RT-PCR is high for RSV detection in home-dwelling older adults. In all cases with discordant results for the two assays, viral load was low. In part two of this thesis I discussed the burden and dynamics of respiratory viruses in infants. Results are based on a hospital based cohort and two different birth cohort studies. In Chapter 4 we examined the occurrence of respiratory viruses in infants during the first year of life. Rhinovirus (RV) was negatively associated with ARTI (aOR 0.41 [95% CI 0.18-0.92]). Human metapneumovirus, RSV, parainfluenza (PIV) 2 and 4, and human coronavirus (HCoV) HKU1 were positively associated with ARTI. Asymptomatic RV in early life was, however, associated with increased susceptibility to and recurrence of ARTIs later in the first year of life (Kaplan-Meier survival analysis: p=0.022). The methods of the prospective international RESCEU birth cohort study was described in Chapter 5. The primary outcome was the incidence of RSV associated ARTI, medically attended (MA)-ARTI, and hospitalisation in the first year of life. The results of this study were shown in Chapter 6. In total 9,154 infants born between July 2017 and April 2020 were followed during the first year of life of whom 993 participated in the nested active surveillance. The incidence of RSV hospitalisation in the total cohort was 1.8% (95% CI 1.6-2.1). About half of hospitalisations for respiratory tract infection in the first year of life were associated with RSV. The majority (57.9%) of RSV hospitalizations occurred in children <3 months of age. Incidences of RSV infection and medically-attended RSV infection in the active surveillance cohort were 26.2% (95% CI 24.0-28.6) and 14.1% (95% CI 12.3-16.0), respectively. The burden of influenza and RSV in infants of the Dutch part of RESCEU was discussed in Chapter 7. RSV was responsible for the highest number of ARTIs in both non-hospitalised and hospitalised infants, especially during the first months of life. Incidence of influenza-ARTI was low compared to RSV-ARTI.