Piero Poletti, Marcello Tirani, Danilo Cereda, Filippo Trentini, Giorgio Guzzetta, Valentina Marziano, Sabrina Buoro, Simona Riboli, Lucia Crottogini, Raffaella Piccarreta, Alessandra Piatti, Giacomo Grasselli, Alessia Melegaro, Maria Gramegna, Marco Ajelli, Stefano Merler
We analyzed 5,484 close contacts of COVID-19 cases from Italy, all of them tested for SARS-CoV-2 infection. We found an infection fatality ratio of 2.2% (95%CI 1.69-2.81%) and identified male sex, age >70 years, cardiovascular comorbidities, and infection early in the epidemics as risk factors for death.
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The fatality rate of Covid-19 escalates with age and is larger in men than women. I show that these variations correlate strongly with the level of the viral receptor protein ACE2 in rat lungs, which is consistent with the still limited and apparently contradictory data on human ACE2. Surprisingly, lower levels of the receptor correlate with higher fatality. However, a previous mathematical model predicts that the speed of viral progression in the organism has a maximum and then declines with the receptor level. Moreover, many manifestations of severe CoViD-19, such as severe lung injury, exac…
Relevance: Laboratory diagnosis of the novel coronavirus (SARS-CoV-2) infection combined with quarantine for contacts of infected individuals affects the spread of SARS-CoV-2 infection and levels of related mortality. Practices for testing for SARS-CoV-2 infection vary geographically in Russia. For example, in the city of St. Petersburg, where mortality rate for COVID-19 is the highest in the Russian Federation on Oct. 25, 2020, every death for COVID-19 corresponds to 15.7 detected cases of COVID-19 in the population, while the corresponding number for the whole of Russia is 58.1, suggesting l…
Several European countries have suspended the inoculation of the AstraZeneca vaccine out of suspicion of causing deep vein thrombosis. In this letter we report some Fermi estimates performed using a stochastic model aimed at making a risk-benefit analysis of the interruption of the delivery of the AstraZeneca vaccine in France and Italy. Our results clearly show that excess deaths due to the interruption of the vaccination campaign injections largely overrun those due to thrombosis even in worst case scenarios of frequency and gravity of the vaccine side effects.
Different ways of calculating mortality ratios during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misint…
Understanding Covid-19 lethality and its variation from country to country is essential for supporting governments in the choice of appropriate strategies. Adopting correct indicators to monitor the lethality of the infection in the course of the outbreak is a crucial issue. This works highlights how far the time-dependent case fatality rate is a misleading indicator for estimating the fatality in the course of the outbreak, even if our attention is only restricted to the subset of confirmed cases. Our analysis proves that the final case fatality ratio for several major European countries is b…
In this letter we study the temporal evolution of the Sars-Cov-2 in Italy. The time window of the real data is between February 24 and March 25. After we upgrade the data until April 1.We perform the analysis with 4 different model and we think that the best candidate to describe correctly the italian situation is a generalized Logistic equation. We use two coupled differential equations that describe the evolution of the severe infected and the deaths. We have done this choice, because in Italy the pharyngeal swabs are made only to severe infected and so we have no information about asymptoma…
In a previous article [1] we have described the temporal evolution of the Sars- Cov-2 in Italy in the time window February 24-April 1. As we can see in [1] a generalized logistic equation captures both the peaks of the total infected and the deaths. In this article our goal is to study the missing peak, i.e. the currently infected one (or total currently positive). After the April 7 the large increase in the number of swabs meant that the logistical behavior of the infected curve no longer worked. So we decided to generalize the model, introducing new parameters. Moreover, we adopt a similar a…
In the absence of other tools, monitoring the effects of protective measures, including social distancing and forecasting the outcome of outbreaks is of immense interest. Real-time data is noisy and very often hampered by systematic errors in reporting. Detailed epidemic models may contain a large number of empirical parameters, which cannot be determined with sufficient accuracy. In this paper, we show that the cumulative number of deaths can be regarded as a master variable, and the parameters of the epidemic such as the basic reproduction number, the size of the susceptible population, and …
We comparatively analyzed the spatiotemporal fluctuations of the 2019-novel coronavirus (COVID-19) and SARS outbreaks to understand their epidemiological characteristics. Methodologically, we introduced TPL (Taylor power law) to characterize their spatiotemporal heterogeneity/stability and Hubbell (2001) unified neutral theory of biodiversity (UNTB) [specifically Harris et al. (2015) HDP-MSN model (hierarchical Dirichlet process multi-site neutral model)] to approximate the metapopulation of coronavirus infections. First, TPL analysis suggested that the coronaviruses appear to have a specific …
We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 °C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at …
The 2019-Novel-Coronavirus (COVID-19) has affected 116 countries (By March 12) and out of more than 118,000 confirmed cases. Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-03-12; daily upd…
While the SARS-CoV-2 keeps spreading world-wide, comparing its evolution across different nations is a timely challenge of both theoretical and practical importance. The large variety of dissimilar and country-dependent epidemiological factors, in fact, makes extremely difficult to understand their influence on the epidemic trends within a unique and coherent framework. We present a geometric framework to characterize, in an integrated and low-dimensional fashion, the epidemic plume-like trajectories traced by the infection rate, $I$, and the fatality rate, $D$, in the $(I,D)$ plane. Our analy…
I use a very simple deterministic model for the spread of Covid-19 in a large population. Using this to compare the relative decay of the number of deaths per day between different regions in Italy, Spain and England, each applying in principle the same social distancing procedures across the whole country, I obtain an estimate of the total fraction of the population which had already become infected by April 10th. In the most heavily affected regions, Lombardy, Madrid and London, this fraction is higher than expected, i.e. $\approx 0.3$. This result can then be converted to a determination of…
Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to under-ascertainment of asymptomatic and mild-disease cases. In this work, we quantify age-specific probabilities of transitions between stages defining the natural history of SARS-CoV-2 infection from 1,965 SARS-CoV-2 positive individuals identified in Italy between March and April 2020 among contacts of confirmed cases. Infected contacts of cases were confirmed via RT-PCR tests as part of contact tracing activities or retrospectively via IgG serological tests and followed-up for symptoms and clini…
We give some numerical observations on the total number of infected by the SARS-CoV-2 in Italy. The analysis is based on a tanh formula involving two parameters. A polynomial correlation between the parameters gives an upper bound for the time of the peak of new infected. A numerical indicator of the temporal variability of the upper bound is introduced. The result and the possibility to extend the analysis to other countries are discussed in the conclusions.
Besides maintaining health precautions, vaccination has been the only prevention from SARS-CoV-2, though no clinically proved 100% effective vaccine has been developed till date. At this stage, to withhold the debris of this pandemic, experts need to know the impact of the vaccine efficacy rate's threshold and how long this pandemic may extent with vaccines that have different efficacy rates. In this article, a mathematical model study has been done on the importance of vaccination and vaccine efficiency rate during an ongoing pandemic. We simulated a five compartment mathematical model to ana…
SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the `universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antib…
The identification of the transmission parameters of a virus is fundamental to identify the optimal public health strategy. These parameters can present significant changes over time caused by genetic mutations or viral recombination, making their continuous monitoring fundamental. Here we present a method, suitable for this task, which uses as unique information the daily number of reported cases. The method is based on a time since infection model where transmission parameters are obtained by means of an efficient maximization procedure of the likelihood. Applying the method to SARS-CoV-2 da…
Understanding the behaviour of hosts of SARS-CoV-2 is crucial to our understanding of the virus. A comparison of environmental features related to the incidence of SARS-CoV-2 with those of its potential hosts is critical. We examine the distribution of coronaviruses among bats. We analyse the distribution of SARS-CoV-2 in a nine-week period following lockdown in Italy, Spain, and Australia. We correlate its incidence with environmental variables particularly ultraviolet radiation, temperature, and humidity. We establish a clear negative relationship between COVID-19 and ultraviolet radiation, …
We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model and second: a partially observable Markov Decision Process (MDP) or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (S0), as well as epidemic parameters. Parameter estimati…
This work provides an overview on deterministic and stochastic models that have previously been proposed by us to study the transmission dynamics of the Coronavirus Disease 2019 (COVID-19) in Europe and USA. Briefly, we describe realistic deterministic and stochastic models for the evolution of the COVID-19 pandemic, subject to the lockdown and quarantine measures, which take into account the time-delay for recovery or death processes. Realistic dynamic equations for the entire process have been derived by adopting the so-called "kinetic-type reactions approach". The lockdown and the quarantin…
The Italian government has been one of the most responsive to COVID-19 emergency, through the adoption of quick and increasingly stringent measures to contain the outbreak. Despite this, Italy has suffered a huge human and social cost, especially in Lombardy. The aim of this paper is dual: i) first, to investigate the reasons of the case fatality rate (CFR) differences across Italian 20 regions and 107 provinces, using a multivariate OLS regression approach; and ii) second, to build a taxonomy of provinces with similar mortality risk of COVID-19, by using the Ward hierarchical agglomerative cl…
In this study, we propose a time-dependent Susceptible-Exposed-Infected-Recovered (SEIR) model for the analysis of the SARS-CoV-2 epidemic outbreak in three different countries, the United States of America, Italy and Iceland using public data inherent the numbers of the epidemic wave. Since several types and grades of actions were adopted by the governments, including travel restrictions, social distancing, or limitation of movement, we want to investigate how these measures can affect the epidemic curve of the infectious population. The parameters of interest for the SEIR model were estimate…
There are many sources of data giving information about the number of SARS-CoV-2 infections in the population, but all have major drawbacks, including biases and delayed reporting. For example, the number of confirmed cases largely underestimates the number of infections, deaths lag infections substantially, while test positivity rates tend to greatly overestimate prevalence. Representative random prevalence surveys, the only putatively unbiased source, are sparse in time and space, and the results come with a big delay. Reliable estimates of population prevalence are necessary for understandi…
Initially emerged in the Chinese city Wuhan and subsequently spread almost worldwide causing a pandemic, the SARS-CoV-2 virus follows reasonably well the SIR (Susceptible-Infectious-Recovered) epidemic model on contact networks in the Chinese case. In this paper, we investigate the prediction accuracy of the SIR model on networks also for Italy. Specifically, the Italian regions are a metapopulation represented by network nodes and the network links are the interactions between those regions. Then, we modify the network-based SIR model in order to take into account the different lockdown measu…
Accurate modeling of lockdown effects on SARS-CoV-2 epidemic evolution is a key issue in order e.g. to inform health-care decisions on emergency management. The compartmental and spatial models so far proposed use parametric descriptions of the contact rate, often assuming a time-invariant effect of the lockdown. In this paper we show that these assumptions may lead to erroneous evaluations on the ongoing pandemic. Thus, we develop a new class of nonparametric compartmental models able to describe how the impact of the lockdown varies in time. Exploiting regularization theory, hospitalized dat…
Background. The paper concerns the SARS-CoV2 (COVID-19) pandemic that, starting from the end of February 2020, began spreading along the Italian peninsula, by first attacking small communities in north regions, and then extending to the center and south of Italy, including the two main islands. Objective. The creation of a forecast model that manages to alert the decision-making bodies and, in particular, the healthcare system, to hinder the emergence of any other pandemic outbreaks, or the arrival of subsequent pandemic waves. Methods. A new mathematical model to describe the pandemic is give…
In late December 2019, a novel strand of Coronavirus (SARS-CoV-2) causing a severe, potentially fatal respiratory syndrome (COVID-19) was identified in Wuhan, Hubei Province, China and is causing outbreaks in multiple world countries, soon becoming a pandemic. Italy has now become the most hit country outside of Asia: on March 16, 2020, the Italian Civil Protection documented a total of 27980 confirmed cases and 2158 deaths of people tested positive for SARS-CoV-2. In the context of an emerging infectious disease outbreak, it is of paramount importance to predict the trend of the epidemic in o…
Mechanistic models fit to streaming surveillance data are critical to understanding the transmission dynamics of an outbreak as it unfolds in real-time. However, transmission model parameter estimation can be imprecise, and sometimes even impossible, because surveillance data are noisy and not informative about all aspects of the mechanistic model. To partially overcome this obstacle, Bayesian models have been proposed to integrate multiple surveillance data streams. We devised a modeling framework for integrating SARS-CoV-2 diagnostics test and mortality time series data, as well as seropreva…
Background: There is a lack of population-based studies on the effectiveness and durability of the SARS-CoV-2-induced immune protection during the Omicron wave. Methods: This retrospective study included 470 159 cases aged 60 years or older, who tested positive for SARS-CoV-2 between January 1 and June 30, 2022 in Bavaria, Germany. We examined time to death, measured from the earliest date of reporting/symptom onset until day 60. Cox models were used to estimate adjusted hazard ratios (HR) for sex, age, earliest calendar date of documented infection, and level of vaccine-induced or hybrid immu…
Predictability of viral load dynamics in the early phases of SARS-CoV-2 through a model-based approach
本文提出了一种基于模型的方法，通过分析真实数据和感染动态的多尺度结构，预测SARS-CoV-2早期阶段的病毒载量动态。
COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number o…
Background School closures and distance learning have been extensively applied to control SARS-CoV-2 transmission. Despite evidence of viral circulation in schools, the contribution of students and of in-person schooling to the transmission remains poorly quantified. Methods We analyze 976 exposure events, involving 460 positive individuals, as identified in early 2021 by routine surveillance and through an extensive screening conducted on students, school personnel, and their household members during an outbreak in a small municipality of Italy. Results From the analysis of potential transmis…
We study the perception of COVID-2019 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet (on Twitter, Google, YouTube, Wikipedia and electronic media represented by Event Registry) from January 2020 to 12.03.2020 (before and after official introduction to Poland on 04.03.2020). To this end we utilize data mining, social network analysis, natural language processing techniques. Each examined internet platform was analyzed for representativeness and composition of the target group. We identified three temporal major cluster of the interest before dis…
In this paper, it is shown that the Moyal distribution is an excelent tool to study the SARS-Cov-II (Covid-19) epidemiological associated curves and its propagation. The Moyal parameters give all the information to describe the form and the impact of the illness outbreak in the different affected countries and its global impact. We checked that the Moyal distribution can accurately fit the daily report of {\it{new confirmed cases of infected people}} (NCC) per country, in that places where the contagion is reaching their final phase, describing the beginning, the most intense phase and the des…
Background. During 2021, the COVID-19 pandemic was characterized by the emergence of lineages with increased fitness. For most of these variants, quantitative information is scarce on epidemiological quantities such as the incubation period and generation time, which are critical for both public health decisions and scientific research. Method. We analyzed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period using information on negative PCR tests and the date of last exposure fr…
The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in…
Emergent circulation patterns from anonymized mobility data: Clustering Italy in the time of Covid
本文基于匿名移动数据构建意大利省际人员流动网络，通过时空聚类识别封控阶段与稳定移动区域，并验证可推广至其他地区和类似网络的分析流程。
Using a simple economic model in which social-distancing reduces contagion, we study the implications of waning immunity for the epidemiological dynamics and social activity. If immunity wanes, we find that COVID-19 likely becomes endemic and that social-distancing is here to stay until the discovery of a vaccine or cure. But waning immunity does not necessarily change optimal actions on the onset of the pandemic. Decentralized equilibria are virtually independent of waning immunity until close to peak infections. For centralized equilibria, the relevance of waning immunity decreases in the pr…
Understanding how widely COVID-19 has spread is critical for examining the pandemic's progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker t…
Computational models for the simulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic evolution would be extremely useful to support authorities in designing healthcare policies and lockdown measures to contain its impact on public health and economy. In Italy, the devised forecasts have been mostly based on a pure data-driven approach, by fitting and extrapolating open data on the epidemic evolution collected by the Italian Civil Protection Center. In this respect, SIR epidemiological models, which start from the description of the nonlinear interactions between…
Daily Profile of COVID-19 Infections in Germany, throughout the Pandemic
本研究通过德国每日病例数据分析 COVID-19 传播动态，结合流行病学参数估算繁殖数与群体免疫阈值，并预测死亡概况及病例致死率。
Large scale virological testing of SARS-Cov2 is implemented since May 2020 in France. We assume that the positivity of asymptomatic people not being contact cases (ANBC) is representative of the positivity of the whole French population, which allows estimating the real incidence. We estimate, using Santé Public France reports, that the incidence at the beginning of August was about 0.8% and rose to about 2.4% of the total population at the beginning of September. This corresponds to about 1.6 million people simultaneously infected and 230.000 new infections each day. These evaluations allow t…
Background: Rapid testing for an infection is paramount during a pandemic to prevent continued viral spread and excess morbidity and mortality. This study aimed to determine whether alternative testing strategies based on sample pooling can increase the speed and throughput of screening for SARS-CoV-2. Methods: A mathematical modelling approach was chosen to simulate six different testing strategies based on key input parameters (infection rate, test characteristics, population size, testing capacity etc.). The situations in five countries (US, DE, UK, IT and SG) currently experiencing COVID-1…
The world evolution of the Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2 or simply COVID-19) led the World Health Organization to declare it a pandemic. The disease appeared in China in December 2019, and it has spread fast around the world, specially in european countries like Italy and Spain. The first reported case in Brazil was recorded in February 26, and after that the number of cases growed fast. In order to slow down the initial growth of the disease through the country, confirmed positive cases were isolated to not transmit the disease. To better understand the early evol…
Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, wide-scale social distancing including local and national lockdowns. In this technical update, we extend a semi-mechanistic Bayesian hierarchical model that infers the impact of these interventions and estimates the number of infec…
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