Search

When Covid-19 arrived in Italy in early 2020, a group of statisticians came together to provide tools to make sense of the unfolding epidemic and to counter misleading media narratives. Here, members of StatGroup-19 reflect on their work to date

We introduce an extended generalised logistic growth model for discrete outcomes, in which spatial and temporal dependence are dealt with the specification of a network structure within an Auto-Regressive approach. A major challenge concerns the specification of the network structure, crucial to consistently estimate the canonical parameters of the generalised logistic curve, e.g. peak time and height. We compared a network based on geographic proximity and one built on historical data of transport exchanges between regions. Parameters are estimated under the Bayesian framework, using Stan probabilistic programming language. The proposed approach is motivated by the analysis of both the first and the second wave of COVID-19 in Italy, i.e. from February 2020 to July 2020 and from July 2020 to December 2020, respectively. We analyse data at the regional level and, interestingly enough, prove that substantial spatial and temporal dependence occurred in both waves, although strong restrictive measures were implemented during the first wave. Accurate predictions are obtained, improving those of the model where independence across regions is assumed.

Background Residential greenness has been associated with health benefits, but its biological mechanism is largely unknown. Investigation of greenness-related DNA methylation profiles can contribute to mechanistic understanding of the health benefits of residential greenness. Objective To identify DNA methylation profiles associated with greenness in the immediate surroundings of the residence. Methods We analyzed genome-wide DNA methylation in 1938 blood samples (982 participants) from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). We estimated residential greenness based on normalized difference vegetation index at 30 × 30 m cell (green30) and 500 m buffer (green500) around the residential address. We conducted epigenome-wide association study (EWAS) to identify differentially methylated CpGs and regions, and enrichment tests by comparing to the CpGs that previous EWAS identified as associated with allergy, physical activity, and allostatic load-relevant biomarkers. Results We identified no genome-wide significant CpGs, but 163 and 56 differentially methylated regions for green30 and green500, respectively. Green30-related DNA methylation profiles showed enrichments in allergy, physical activity, and allostatic load, while green500-related methylation was enriched in allergy and allostatic load. Conclusions Residential greenness may have health impacts through allergic sensitization, stress coping, or behavioral changes. Exposure to more proximal greenness may be more health-relevant.

The use of network analysis to investigate social structures has recently seen a rise due to the high availability of data and the numerous insights it can provide into different fields. Most analyses focus on the topological characteristics of networks and the estimation of relationships between the nodes. We adopt a different perspective by considering the whole network as a random variable conveying the effect of an exposure on a response. This point of view represents a classical mediation setting, where the interest lies in estimating the indirect effect, that is, the effect propagated through the mediating variable. We introduce a latent space model mapping the network into a space of smaller dimension by considering the hidden positions of the units in the network. The coordinates of each node are used as mediators in the relationship between the exposure and the response. We further extend mediation analysis in the latent space framework by using Generalised Linear Models instead of linear ones, as previously done in the literature, adopting an approach based on derivatives to obtain the effects of interest. A Bayesian approach allows us to get the entire distribution of the indirect effect, generally unknown, and compute the corresponding highest density interval, which gives accurate and interpretable bounds for the mediated effect. Finally, an application to social interactions among a group of adolescents and their attitude toward substance use is presented.

We compare the expected all-cause mortality with the observed one for different age classes during the pandemic in Lombardy, which was the epicenter of the epidemic in Italy and still is the region most affected by the pandemic. A generalized linear mixed model is introduced to model weekly mortality from 2011 to 2019, taking into account seasonal patterns and year-specific trends. Based on the 2019 year-specific conditional best linear unbiased predictions, a significant excess of mortality is estimated in 2020, leading to approximately 35000 more deaths than expected, mainly arising during the first wave. In 2021, instead, the excess mortality is not significantly different from zero, for the 85+ and 15-64 age classes, and significant reductions with respect to the 2020 estimated excess mortality are estimated for other age classes.

A novel parametric regression model is proposed to fit incidence data typically collected during epidemics. The proposal is motivated by real-time monitoring and short-term forecasting of the main epidemiological indicators within the first outbreak of COVID-19 in Italy. Accurate short-term predictions, including the potential effect of exogenous or external variables are provided. This ensures to accurately predict important characteristics of the epidemic (e.g., peak time and height), allowing for a better allocation of health resources over time. Parameter estimation is carried out in a maximum likelihood framework. All computational details required to reproduce the approach and replicate the results are provided. publishedVersion

The availability of intensive care beds during the COVID‐19 epidemic is crucial to guarantee the best possible treatment to severely affected patients. In this work we show a simple strategy for short‐term prediction of COVID‐19 intensive care unit (ICU) beds, that has proved very effective during the Italian outbreak in February to May 2020. Our approach is based on an optimal ensemble of two simple methods: a generalized linear mixed regression model, which pools information over different areas, and an area‐specific nonstationary integer autoregressive methodology. Optimal weights are estimated using a leave‐last‐out rationale. The approach has been set up and validated during the first epidemic wave in Italy. A report of its performance for predicting ICU occupancy at regional level is included.

Although evidence for the heterogeneity of asthma accumulated, consensus for definitions of asthma phenotypes is still lacking. Obesity may have heterogeneous effects on various asthma phenotypes. We aimed to distinguish asthma phenotypes by latent class analysis and to investigate their associations with different obesity parameters in adults using a population-based Swiss cohort (SAPALDIA). We applied latent class analysis to 959 self-reported asthmatics using information on disease activity, atopy, and age of onset. Associations with obesity were examined by multinomial logistic regression, after adjustments for age, sex, smoking status, educational level, and study centre. Body mass index, percent body fat, waist hip ratio, waist height ratio, and waist circumference were used as obesity measure. Four asthma classes were identified, including persistent multiple symptom-presenting asthma (nÂ=Â122), symptom-presenting asthma (nÂ=Â290), symptom-free atopic asthma (nÂ=Â294), and symptom-free non-atopic asthma (nÂ=Â253). Obesity was positively associated with symptom-presenting asthma classes but not with symptom-free ones. Percent body fat showed the strongest association with the persistent multiple symptom-presenting asthma. We observed heterogeneity of associations with obesity across asthma classes, indicating different asthma aetiologies.

A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-&kappa, B signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.

This working paper has a twofold goal. On one hand, it provides a recap of Linear Mixed Models (LMMs): far from trying to be exhaustive, this first part of the working paper focusses on the derivation of theoretical results on estimation of LMMs that are scattered in the literature or whose mathematical derivation is sometimes missing or too quickly sketched. On the other hand, it discusses various definitions that are available in the literature for the hat-matrix of Linear Mixed Models, showing their limitations and proving their equivalence.

Bivariate ordered logistic models (BOLMs) are appealing to jointly model the marginal distribution of two ordered responses and their association, given a set of covariates. When the number of categories of the responses increases, the number of global odds ratios to be estimated also increases, and estimation gets problematic. In this work we propose a non-parametric approach for the maximum likelihood (ML) estimation of a BOLM, wherein penalties to the differences between adjacent row and column effects are applied. Our proposal is then compared to the Goodman and Dale models. Some simulation results as well as analyses of two real data sets are presented and discussed.

Matrix-valued distributions are used in continuous multivariate analysis to model sample data matrices of continuous measurements; their use seems to be neglected for binary, or more generally categorical, data. In this paper we propose a matrix-valued Bernoulli distribution, based on the log-linear representation introduced by Cox [The analysis of multivariate binary data, Appl. Statist. 21 (1972) 113–120] for the Multivariate Bernoulli distribution with correlated components.

We compare the expected all-cause mortality with the observed one for different age classes during the pandemic in Lombardy, which was the epicenter of the epidemic in Italy. The first case in Italy was found in Lombardy in early 2020, and the first wave was mainly centered in Lombardy. The other three waves, in Autumn 2020, March 2021 and Summer 2021 are also characterized by a high number of cases in absolute terms. A generalized linear mixed model is introduced to model weekly mortality from 2011 to 2019, taking into account seasonal patterns and year-specific trends. Based on the 2019 year-specific conditional best linear unbiased predictions, a significant excess of mortality is estimated in 2020, leading to approximately 35000 more deaths than expected, mainly arising during the first wave. In 2021, instead, the excess mortality is not significantly different from zero, for the 85+ and 15–64 age classes, and significant reductions with respect to the 2020 estimated excess mortality are estimated for other age classes. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-021-02060-1.