What is known
•Adults with comorbidities are more likely to suffer from severe manifestations of COVID-19•Children with COVID-19 have less severe disease manifestations than adults•Children may ...experience multisystem inflammatory syndrome due to COVID-19
What is new
•Children with comorbidities may be at an increased risk for PICU admission and/or severe COVID-19•Children with comorbidities may be at an increased risk of mortality during COVID-19 infection•Childhood obesity likely contributes to more serious manifestations of COVID-19
There is limited information on the severity of COVID-19 infection in children with comorbidities. We investigated the effects of pediatric comorbidities on COVID-19 severity by means of a systematic review and meta-analysis of published literature.
PubMed, Embase, and Medline databases were searched for publications on pediatric COVID-19 infections published January 1st to October 5th, 2020. Articles describing at least one child with and without comorbidities, COVID-19 infection, and reported outcomes were included.
42 studies containing 275,661 children without comorbidities and 9,353 children with comorbidities were included. Severe COVID-19 was present in 5.1% of children with comorbidities, and in 0.2% without comorbidities. Random-effects analysis revealed a higher risk of severe COVID-19 among children with comorbidities than for healthy children; relative risk ratio 1.79 (95% CI 1.27 – 2.51; I2 = 94%). Children with underlying conditions also had a higher risk of COVID-19-associated mortality; relative risk ratio 2.81 (95% CI 1.31 – 6.02; I2 = 82%). Children with obesity had a relative risk ratio of 2.87 (95% CI 1.16 – 7.07; I2 = 36%).
Children with comorbidities have a higher risk of severe COVID-19 and associated mortality than children without underlying disease. Additional studies are required to further evaluate this relationship.
Complex, highly-computational, individual-based models are abundant in epidemiology. For epidemics such as macro-parasitic diseases, detailed modelling of human behaviour and pathogen life-cycle are ...required in order to produce accurate results. This can often lead to models that are computationally-expensive to analyse and perform model fitting, and often require many simulation runs in order to build up sufficient statistics. Emulation can provide a more computationally-efficient output of the individual-based model, by approximating it using a statistical model. Previous work has used Gaussian processes (GPs) in order to achieve this, but these can not deal with multi-modal, heavy-tailed, or discrete distributions. Here, we introduce the concept of a mixture density network (MDN) in its application in the emulation of epidemiological models. MDNs incorporate both a mixture model and a neural network to provide a flexible tool for emulating a variety of models and outputs. We develop an MDN emulation methodology and demonstrate its use on a number of simple models incorporating both normal, gamma and beta distribution outputs. We then explore its use on the stochastic SIR model to predict the final size distribution and infection dynamics. MDNs have the potential to faithfully reproduce multiple outputs of an individual-based model and allow for rapid analysis from a range of users. As such, an open-access library of the method has been released alongside this manuscript.
Public health mitigation strategies in British Columbia during the pandemic included stay-at-home orders and closure of non-essential services. While most primary physicians' offices were closed, ...hospitals prepared for a pandemic surge and emergency departments (EDs) stayed open to provide care for urgent needs. We sought to determine whether ED paediatric presentations prior and during the COVID-19 pandemic changed and review acuity compared with seasonal adjusted prior year.
We analysed records from 18 EDs in British Columbia, Canada, serving 60% of the population. We included children 0-16 years old and excluded those with no recorded acuity or discharge disposition and those left without being seen by a physician. We compared prepandemic (before the first COVID-19 case), early pandemic (after first COVID-19 case) and peak pandemic (during public health emergency) periods as well as a similar time from the previous year.
A reduction of 57% and 70% in overall visits was recorded in the children's hospital ED and the general hospitals EDs, respectively. Average daily visits declined significantly during the peak-pandemic period (167.44±40.72) compared with prepandemic period (543.53±58.8). Admission rates increased mainly due to the decrease in the rate of visits with lower acuity. Children with complaints of 'fever' and 'gastrointestinal' symptoms had both the largest overall volume and per cent reduction in visits between peak-pandemic and prior year (79% and 74%, respectively).
Paediatric emergency medicine attendances were reduced to one-third of normal numbers during the 2020 COVID-19 lockdown in British Columbia, Canada, with the reduction mainly seen in minor illnesses that do not usually require admission.
The outbreak of the severe acute respiratory syndrome coronavirus 2 started in Wuhan, China, towards the end of 2019 and spread worldwide. The rapid spread of the disease can be attributed to many ...factors including its high infectiousness and the high rate of human mobility around the world. Although travel/movement restrictions and other non-pharmaceutical interventions aimed at controlling the disease spread were put in place during the early stages of the pandemic, these interventions did not stop COVID-19 spread. To better understand the impact of human mobility on the spread of COVID-19 between regions, we propose a hybrid gravity-metapopulation model of COVID-19. Our modeling framework has the flexibility of determining mobility between regions based on the distances between the regions or using data from mobile devices. In addition, our model explicitly incorporates time-dependent human mobility into the disease transmission rate, and has the potential to incorporate other factors that affect disease transmission such as facemasks, physical distancing, contact rates, etc. An important feature of this modeling framework is its ability to independently assess the contribution of each factor to disease transmission. Using a Bayesian hierarchical modeling framework, we calibrate our model to the weekly reported cases of COVID-19 in thirteen local health areas in Metro Vancouver, British Columbia (BC), Canada, from July 2020 to January 2021. We consider two main scenarios in our model calibration: using a fixed distance matrix and time-dependent weekly mobility matrices. We found that the distance matrix provides a better fit to the data, whilst the mobility matrices have the ability to explain the variance in transmission between regions. This result shows that the mobility data provides more information in terms of disease transmission than the distances between the regions.
Extensive non-pharmaceutical and physical distancing measures are currently the primary interventions against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the ...impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing, with the timing of distancing measures informed by survey data on attitudes to distancing and COVID-19. We fit our model to reported COVID-19 cases in British Columbia (BC), Canada, and five other jurisdictions, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimated the impact that physical distancing (social distancing) has had on the contact rate and examined the projected impact of relaxing distancing measures. We found that, as of April 11 2020, distancing had a strong impact in BC, consistent with declines in reported cases and in hospitalization and intensive care unit numbers; individuals practising physical distancing experienced approximately 0.22 (0.11-0.34 90% CI credible interval) of their normal contact rate. The threshold above which prevalence was expected to grow was 0.55. We define the "contact ratio" to be the ratio of the estimated contact rate to the threshold rate at which cases are expected to grow; we estimated this contact ratio to be 0.40 (0.19-0.60) in BC. We developed an R package 'covidseir' to make our model available, and used it to quantify the impact of distancing in five additional jurisdictions. As of May 7, 2020, we estimated that New Zealand was well below its threshold value (contact ratio of 0.22 0.11-0.34), New York (0.60 0.43-0.74), Washington (0.84 0.79-0.90) and Florida (0.86 0.76-0.96) were progressively closer to theirs yet still below, but California (1.15 1.07-1.23) was above its threshold overall, with cases still rising. Accordingly, we found that BC, New Zealand, and New York may have had more room to relax distancing measures than the other jurisdictions, though this would need to be done cautiously and with total case volumes in mind. Our projections indicate that intermittent distancing measures-if sufficiently strong and robustly followed-could control COVID-19 transmission. This approach provides a useful tool for jurisdictions to monitor and assess current levels of distancing relative to their threshold, which will continue to be essential through subsequent waves of this pandemic.
Summary Background Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two ...pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to clear the transmissible stage of the helminth completely in treated individuals. The aim of this study was to use modelling to assess the potential value of mass drug administration with the triple-drug regimen for accelerating elimination of lymphatic filariasis in different epidemiological settings. Methods We used three different transmission models to compare the number of rounds of mass drug administration needed to achieve a prevalence of microfilaraemia less than 1% with the triple-drug regimen and with current two-drug regimens. Findings In settings with a low baseline prevalence of lymphatic filariasis (5%), the triple-drug regimen reduced the number of rounds of mass drug administration needed to reach the target prevalence by one or two rounds, compared with the two-drug regimen. For areas with higher baseline prevalence (10–40%), the triple-drug regimen strikingly reduced the number of rounds of mass drug administration needed, by about four or five, but only at moderate-to-high levels of population coverage (>65%) and if systematic non-adherence to mass drug administration was low. Interpretation Simulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme. Funding Bill & Melinda Gates Foundation.
•Negative vaccine effectiveness (VE) has been reported for COVID-19.•These measurements likely stem from various biases.•Negative VE signals that estimates across observational studies may also be ...biased.•Suspected false-negative VE requires an investigation of potential biases.
Since the emergence of the SARS-CoV-2 Omicron variant, multiple observational studies have reported negative vaccine effectiveness (VE) against infection, symptomatic infection, and even severity (hospitalization), potentially leading to an interpretation that vaccines were facilitating infection and disease. However, current observations of negative VE likely stem from the presence of various biases (e.g., exposure differences, testing differences). Although negative VE is more likely to arise when true biological efficacy is generally low and biases are large, positive VE measurements can also be subject to the same mechanisms of bias. In this perspective, we first outline the different mechanisms of bias that could lead to false-negative VE measurements and then discuss their ability to potentially influence other protection measurements. We conclude by discussing the use of suspected false-negative VE measurements as a signal to interrogate the estimates (quantitative bias analysis) and to discuss potential biases when communicating real-world immunity research.
Background
GetCheckedOnline is an internet-based screening service aiming to increase HIV testing among gay, bisexual and other men who have sex with men (GBMSM). We assessed the cost-effectiveness ...of GetCheckedOnline in its first implementation phase at different uptake scenarios compared to clinic-based screening services alone in Metro Vancouver, Canada.
Methods
From a healthcare payer’s perspective, our cost-utility analysis used an established dynamic GBMSM HIV compartmental model estimating the probability of acquiring HIV, progressing through diagnosis, disease stages and treatment over a 30-year time horizon. The base case scenario assumed 4.7% uptake of GetCheckedOnline in 2016 (remainder using clinic-based services), with 74% of high-risk and 44% of low-risk infrequent testers becoming regular testers in five years. Scenario analyses tested increased GetCheckedOnline uptake to 10% and 15%.
Results
The cost per test for GetCheckedOnline was $29.40 compared to clinic-based services $56.92. Compared with clinic-based screening services, the projected increase in testing frequency with 4.7% uptake of GetCheckedOnline increased the costs by $329,600 (95% Credible Interval: -$498,200, $571,000) and gained 4.53 (95%CrI: 0, 9.20) quality-adjusted life years (QALYs) in a 30-year time horizon. The probability of GetCheckedOnline being cost-effective was 34% at the threshold of $50,000 per QALY, and increased to 73% at the threshold of $100,000 per QALY. The results were consistent in the other uptake scenarios. The probability of GetCheckedOnline being cost-effective became 80% at the threshold of $50,000 per QALY if assuming 5-year time horizon.
Conclusions
GetCheckedOnline is almost half the cost of clinic-based services on a per-test basis. However, increased access to testing should be balanced with risk profiles of patients to ensure the implementation can be a cost-effective strategy for increasing HIV screening among GBMSM in Metro Vancouver. Additional analyses are needed to understand the impact of internet-based screening including screening for other STIs and in other populations.
Background and aims
The province of British Columbia (BC) Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last 4 years, with a provincial emergency declared in ...April 2016. These deaths have been driven primarily by the introduction of synthetic opioids into the illicit opioid supply. This study aimed to measure the combined impact of large‐scale opioid overdose interventions implemented in BC between April 2016 and December 2017 on the number of deaths averted.
Design
We expanded on the mathematical modelling methodology of our previous study to construct a Bayesian hierarchical latent Markov process model to estimate monthly overdose and overdose‐death risk, along with the impact of interventions.
Setting and Cases
Overdose events and overdose‐related deaths in BC from January 2012 to December 2017.
Interventions
The interventions considered were take‐home naloxone kits, overdose prevention/supervised consumption sites and opioid agonist therapy
Measurements
Counterfactual simulations were performed with the fitted model to estimate the number of death events averted for each intervention and in combination.
Findings
Between April 2016 and December 2017, BC observed 2177 overdose deaths (77% fentanyl‐detected). During the same period, an estimated 3030 (2900–3240) death events were averted by all interventions combined. In isolation, 1580 (1480–1740) were averted by take‐home naloxone, 230 (160–350) by overdose prevention services and 590 (510–720) were averted by opioid agonist therapy.
Conclusions
A combined intervention approach has been effective in averting overdose deaths during British Columbia's opioid overdose crisis in the period since declaration of a public health emergency (April 2016–December 2017). However, the absolute numbers of overdose deaths have not changed.
The evolving proportion of the population considered immunologically naive versus primed for more efficient immune memory response to SARS-CoV-2 has implications for risk assessment. We sought to ...chronicle vaccine- and infection-induced seroprevalence across the first 7 waves of the COVID-19 pandemic in British Columbia, Canada.
During 8 cross-sectional serosurveys conducted between March 2020 and August 2022, we obtained anonymized residual sera from children and adults who attended an outpatient laboratory network in the Lower Mainland (Greater Vancouver and Fraser Valley). We used at least 3 immunoassays per serosurvey to detect SARS-CoV-2 spike and nucleocapsid antibodies. We assessed any seroprevalence (vaccineor infection-induced, or both), defined by positivity on any 2 assays, and infection-induced seroprevalence, also defined by dual-assay positivity but requiring both antinucleocapsid and antispike detection. We used estimates of infection-induced seroprevalence to explore underascertainment of infections by surveillance case reports.
By January 2021, we estimated that any seroprevalence remained less than 5%, increasing with vaccine rollout to 56% by May-June 2021, 83% by September-October 2021 and 95% by March 2022. Infection-induced seroprevalence remained less than 15% through September-October 2021, increasing across Omicron waves to 42% by March 2022 and 61% by July-August 2022. By August 2022, 70%-80% of children younger than 20 years and 60%-70% of adults aged 20-59 years had been infected, but fewer than half of adults aged 60 years and older had been infected. Compared with estimates of infection-induced seroprevalence, surveillance case reports underestimated infections 12-fold between September 2021 and March 2022 and 92-fold between March 2022 and August 2022.
By August 2022, most children and adults younger than 60 years had evidence of both SARS-CoV-2 vaccination and infection. As previous evidence suggests that a history of both exposures may induce stronger, more durable hybrid immunity than either exposure alone, older adults - who have the lowest infection rates but highest risk of severe outcomes - continue to warrant prioritized vaccination.
PDF
