ABSTRACT
BackgroundRespiratory syncytial virus (RSV) is a leading cause of respiratory tract infections and bronchiolitis in young children. The seasonal pattern of RSV is shaped by short-lived immunity, seasonally varying contact rates and pathogen viability. The magnitude of each of these parameters is not fully clear. The disruption of the regular seasonality of RSV during the COVID pandemic in 2020 due to control measures, and the ensuing delayed surge in RSV cases provides an opportunity to disentangle these factors and to understand the implication for vaccination strategies. A better understanding of the drivers of RSV seasonality is key for developing future vaccination strategies. MethodsWe developed a mathematical model of RSV transmission, which simulates the sequential re-infection (SEIRRS4) and uses a flexible Von Mises function to model the seasonal forcing. Using MCMC we fit the model to laboratory confirmed RSV data from 2010-2022 from NSW while accounting for the reduced contact rates during the pandemic with Google mobility data. We estimated the baseline transmission rate, its amplitude and shape during RSV season as well as the duration of immunity. The resulting parameter estimates were compared to a fit to pre-pandemic data only, and to a fit with a cosine forcing function. We then simulated the expected shifts in peak timing and amplitude under two vaccination strategies: continuous and seasonal vaccination. ResultsWe estimate that RSV dynamics in NSW can be best explained by a high effective baseline transmission rate (2.94/d, 95% CrI 2.72-3.19) and a narrow peak with a maximum 13% increase compared to the baseline transmission rate. We also estimate the duration of post infection temporary but sterilizing immunity to be 412 days (95% CrI 391-434). A cosine forcing resulted in a similar fit and posterior estimates. Excluding the data from the pandemic period in the fit increased parameter correlation and yielded less informative posterior distributions. The continuous vaccination strategy led to more extreme seasonal incidence with a delay in the peak timing and a higher amplitude whereas seasonal vaccination flattened the incidence curves. ConclusionQuantifying the parameters that govern RSV seasonality is key in determining potential indirect effects from immunization strategies as those are being rolled out in the next few years.
ABSTRACT
BackgroundLong-term health sequelae of the coronavirus disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on more than 45 percent of the German population from January 2019 through December 2020, we investigated post COVID-19 in children/adolescents and adults. MethodsFrom a total of 38 million individuals, we identified all patients with laboratory confirmed diagnosis of COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age, sex, and propensity score matching on prevalent medical conditions. COVID-19 and control cohorts were followed for incident morbidity outcomes documented at least three months after the date of COVID-19 diagnosis, which was used as the index date for both groups. Overall, 96 pre-defined outcomes were aggregated into 13 diagnosis/symptom complexes and three domains (physical health, mental health, physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95%-confidence intervals (95%-CI). ResultsThe study population included 157,134 individuals (11,950 children/adolescents and 145,184 adults) with confirmed COVID-19. COVID-19 and control cohort were well-balanced regarding covariates. For all health outcomes combined, incidence rates (IRs) in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR=1.30, 95%-CI=[1.25-1.35], IR COVID-19=436.91, IR Control=335.98) and adults (IRR=1.33, 95%-CI=[1.31-1.34], IR COVID-19=615.82, IR Control=464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, incidence rates were significantly higher in all 13 diagnosis/symptom complexes in adults and in ten diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for the age groups 0-11 and 12-17. Incidence rates in children/adolescents were consistently lower than those in adults. Among the specific outcomes with the highest IRR and an incidence rate of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR=2.28, 95%-CI=[1.71-3.06], IR COVID-19=12.58, IR Control=5.51), cough (IRR=1.74, 95%-CI=[1.48-2.04], IR COVID-19=36.56, IR Control=21.06), and throat/chest pain (IRR=1.72, 95%-CI=[1.39-2.12], IR COVID-19=20.01, IR Control=11.66). In adults, these included dysgeusia (IRR=6.69, 95%-CI=[5.88-7.60], IR COVID-19=12.42, IR Control=1.86), fever (IRR=3.33, 95%-CI=[3.01-3.68], IR COVID-19=11.53, IR Control=3.46), and dyspnea (IRR=2.88, 95%-CI=[2.74-3.02], IR COVID-19=43.91, IR Control=15.27). ConclusionsThis large, matched cohort study indicates substantial new-onset post COVID-19 morbidity in pediatric and adult populations based on routine health care documentation. Further investigation is required to assess the persistence and long-term health impact of post COVID-19 conditions, especially in children and adolescents.
