Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible-Exposed-Infected-Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number ([Formula: see text] = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about 200,000 individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

/pdf/spread-and-dynamics-of-the-covid-19-epidemic-in-italy-2rtidiwkfq.pdf

Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures.

In this paper, we study the effectiveness of the modelling approach on the pandemic due to the spreading of the novel COVID-19 disease and develop a susceptible-infected-removed (SIR) model that provides a theoretical framework to investigate its spread within a community Here, the model is based upon the well-known susceptible-infected-removed (SIR) model with the difference that a total population is not defined or kept constant per se and the number of susceptible individuals does not decline monotonically To the contrary, as we show herein, it can be increased in surge periods! In particular, we investigate the time evolution of different populations and monitor diverse significant parameters for the spread of the disease in various communities, represented by China, South Korea, India, Australia, USA, Italy and the state of Texas in the USA The SIR model can provide us with insights and predictions of the spread of the virus in communities that the recorded data alone cannot Our work shows the importance of modelling the spread of COVID-19 by the SIR model that we propose here, as it can help to assess the impact of the disease by offering valuable predictions Our analysis takes into account data from January to June, 2020, the period that contains the data before and during the implementation of strict and control measures We propose predictions on various parameters related to the spread of COVID-19 and on the number of susceptible, infected and removed populations until September 2020 By comparing the recorded data with the data from our modelling approaches, we deduce that the spread of COVID-19 can be under control in all communities considered, if proper restrictions and strong policies are implemented to control the infection rates early from the spread of the disease

A SIR model assumption for the spread of COVID-19 in different communities

The efficacy of social distance and ventilation effectiveness in preventing COVID-19 transmission

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous challenge to healthcare systems in affected communities. Older patients and those with pre-existing medical conditions have been identified as populations at risk of a severe disease course. It remains unclear at this point to what extent chronic liver diseases should be considered as risk factors, due to a shortage of appropriate studies. However, patients with advanced liver disease and those after liver transplantation represent vulnerable patient cohorts with an increased risk of infection and/or a severe course of COVID-19. In addition, the current pandemic requires unusual allocation of healthcare resources which may negatively impact the care of patients with chronic liver disease that continue to require medical attention. Thus, the challenge hepatologists are facing is to promote telemedicine in the outpatient setting, prioritise outpatient contacts, avoid nosocomial dissemination of the virus to patients and healthcare providers, and at the same time maintain standard care for patients who require immediate medical attention.

/pdf/care-of-patients-with-liver-disease-during-the-covid-19-13vx4axstv.pdf

Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper

In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.

/pdf/modelling-the-covid-19-epidemic-and-implementation-of-7jq3i1jpq2.pdf

Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy.

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 order to plan an effective control strategy and to determine its impact. This paper proposes a new epidemic model that discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed is important because non-diagnosed individuals are more likely to spread the infection than diagnosed ones, since the latter are typically isolated, and can explain misperceptions of the case fatality rate and of the seriousness of the epidemic phenomenon. Being able to predict the amount of patients that will develop life-threatening symptoms is important since the disease frequently requires hospitalisation (and even Intensive Care Unit admission) and challenges the healthcare system capacity. We show how the basic reproduction number can be redefined in the new framework, thus capturing the potential for epidemic containment. Simulation results are compared with real data on the COVID-19 epidemic in Italy, to show the validity of the model and compare different possible predicted scenarios depending on the adopted countermeasures.

/pdf/a-sidarthe-model-of-covid-19-epidemic-in-italy-3w3iqdiejm.pdf

A SIDARTHE Model of COVID-19 Epidemic in Italy

Despite progress in clinical care for patients with coronavirus disease 2019 (COVID-19)1, population-wide interventions are still crucial to manage the pandemic, which has been aggravated by the emergence of new, highly transmissible variants. In this study, we combined the SIDARTHE model2, which predicts the spread of SARS-CoV-2 infections, with a new data-based model that projects new cases onto casualties and healthcare system costs. Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions (NPIs) have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of the vaccination campaign. Our model predicts that, from April 2021 to January 2022, in a scenario with no vaccine rollout and weak NPIs ([Formula: see text] = 1.27), as many as 298,000 deaths associated with COVID-19 could occur. However, fast vaccination rollouts could reduce mortality to as few as 51,000 deaths. Implementation of restrictive NPIs ([Formula: see text] = 0.9) could reduce COVID-19 deaths to 30,000 without vaccinating the population and to 18,000 with a fast rollout of vaccines. We also show that, if intermittent open-close strategies are adopted, implementing a closing phase first could reduce deaths (from 47,000 to 27,000 with slow vaccine rollout) and healthcare system costs, without substantive aggravation of socioeconomic losses.

/pdf/modeling-vaccination-rollouts-sars-cov-2-variants-and-the-430qo2unil.pdf

Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy.

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy.

Despite the progress in medical care, combined population-wide interventions (such as physical distancing, testing and contact tracing) are still crucial to manage the SARS-CoV-2 pandemic, aggravated by the emergence of new highly transmissible variants. We combine the compartmental SIDARTHE model, predicting the course of COVID-19 infections, with a new data-based model that projects new cases onto casualties and healthcare system costs. Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants, and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions (NPIs) have a higher impact on the epidemic evolution than vaccination, which advocates for the need to keep containment measures in place throughout the vaccination campaign. We also show that, if intermittent open-close strategies are adopted, deaths and healthcare system costs can be drastically reduced, without any aggravation of socioeconomic losses, as long as one has the foresight to start with a closing phase rather than an opening one.

/pdf/vaccination-and-sars-cov-2-variants-how-much-containment-is-f5b7632l12.pdf

Alessandro Di Filippo

Papers

Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy.

A SIDARTHE Model of COVID-19 Epidemic in Italy

Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy.

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy.

Vaccination and SARS-CoV-2 variants: how much containment is still needed? A quantitative assessment.