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1. Comparative epidemiology of five waves of COVID-19 in Mexico, March 2020–August 2022

   https://doi.org/10.1186/s12879-022-07800-w  

   Ascencio-Montiel, Iván de Jesús ; Ovalle-Luna, Oscar David ; Rascón-Pacheco, Ramón Alberto ; Borja-Aburto, Victor Hugo ; Chowell, Gerardo ( October 2022 , BMC Infectious Diseases)

   The Mexican Institute of Social Security (IMSS) is the largest health care provider in Mexico, covering about 48% of the Mexican population. In this report, we describe the epidemiological patterns related to confirmed cases, hospitalizations, intubations, and in-hospital mortality due to COVID-19 and associated factors, during five epidemic waves recorded in the IMSS surveillance system.

   We analyzed COVID-19 laboratory-confirmed cases from the Online Epidemiological Surveillance System (SINOLAVE) from March 29th, 2020, to August 27th, 2022. We constructed weekly epidemic curves describing temporal patterns of confirmed cases and hospitalizations by age, gender, and wave. We also estimated hospitalization, intubation, and hospital case fatality rates. The mean days of in-hospital stay and hospital admission delay were calculated across five pandemic waves. Logistic regression models were employed to assess the association between demographic factors, comorbidities, wave, and vaccination and the risk of severe disease and in-hospital death.

   A total of 3,396,375 laboratory-confirmed COVID-19 cases were recorded across the five waves. The introduction of rapid antigen testing at the end of 2020 increased detection and modified epidemiological estimates. Overall, 11% (95% CI 10.9, 11.1) of confirmed cases were hospitalized, 20.6% (95% CI 20.5, 20.7) of the hospitalized cases were intubated, and the hospital case fatality rate was 45.1% (95% CI 44.9, 45.3). The mean in-hospital stay was 9.11 days, and patients were admitted on average 5.07 days after symptoms onset. The most recent waves dominated by the Omicron variant had the highest incidence. Hospitalization, intubation, and mean hospitalization days decreased during subsequent waves. The in-hospital case fatality rate fluctuated across waves, reaching its highest value during the second wave in winter 2020. A notable decrease in hospitalization was observed primarily among individuals ≥ 60 years. The risk of severe disease and death was positively associated with comorbidities, age, and male gender; and declined with later waves and vaccination status.

   During the five pandemic waves, we observed an increase in the number of cases and a reduction in severity metrics. During the first three waves, the high in-hospital fatality rate was associated with hospitalization practices for critical patients with comorbidities.

    

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2. Development and validation of predictive models for COVID-19 outcomes in a safety-net hospital population

   https://doi.org/10.1093/jamia/ocac062  

   Hao, Boran ; Hu, Yang ; Sotudian, Shahabeddin ; Zad, Zahra ; Adams, William G. ; Assoumou, Sabrina A. ; Hsu, Heather ; Mishuris, Rebecca G. ; Paschalidis, Ioannis C. ( May 2022 , Journal of the American Medical Informatics Association)

   To develop predictive models of coronavirus disease 2019 (COVID-19) outcomes, elucidate the influence of socioeconomic factors, and assess algorithmic racial fairness using a racially diverse patient population with high social needs.

   Data included 7,102 patients with positive (RT-PCR) severe acute respiratory syndrome coronavirus 2 test at a safety-net system in Massachusetts. Linear and nonlinear classification methods were applied. A score based on a recurrent neural network and a transformer architecture was developed to capture the dynamic evolution of vital signs. Combined with patient characteristics, clinical variables, and hospital occupancy measures, this dynamic vital score was used to train predictive models.

   Hospitalizations can be predicted with an area under the receiver-operating characteristic curve (AUC) of 92% using symptoms, hospital occupancy, and patient characteristics, including social determinants of health. Parsimonious models to predict intensive care, mechanical ventilation, and mortality that used the most recent labs and vitals exhibited AUCs of 92.7%, 91.2%, and 94%, respectively. Early predictive models, using labs and vital signs closer to admission had AUCs of 81.1%, 84.9%, and 92%, respectively.

   The most accurate models exhibit racial bias, being more likely to falsely predict that Black patients will be hospitalized. Models that are only based on the dynamic vital score exhibited accuracies close to the best parsimonious models, although the latter also used laboratories.

   This large study demonstrates that COVID-19 severity may accurately be predicted using a score that accounts for the dynamic evolution of vital signs. Further, race, social determinants of health, and hospital occupancy play an important role.

    

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3. Rehabilitation Using Mobile Health for Older Adults With Ischemic Heart Disease in the Home Setting (RESILIENT): Protocol for a Randomized Controlled Trial

   https://doi.org/10.2196/32163  

   Dodson, John A ; Schoenthaler, Antoinette ; Sweeney, Greg ; Fonceva, Ana ; Pierre, Alicia ; Whiteson, Jonathan ; George, Barbara ; Marzo, Kevin ; Drewes, Wendy ; Rerisi, Elizabeth ; et al ( January 2022 , JMIR Research Protocols)

   Background Participation in ambulatory cardiac rehabilitation remains low, especially among older adults. Although mobile health cardiac rehabilitation (mHealth-CR) provides a novel opportunity to deliver care, age-specific impairments may limit older adults’ uptake, and efficacy data are currently lacking. Objective This study aims to describe the design of the rehabilitation using mobile health for older adults with ischemic heart disease in the home setting (RESILIENT) trial. Methods RESILIENT is a multicenter randomized clinical trial that is enrolling patients aged ≥65 years with ischemic heart disease in a 3:1 ratio to either an intervention (mHealth-CR) or control (usual care) arm, with a target sample size of 400 participants. mHealth-CR consists of a commercially available mobile health software platform coupled with weekly exercise therapist sessions to review progress and set new activity goals. The primary outcome is a change in functional mobility (6-minute walk distance), which is measured at baseline and 3 months. Secondary outcomes are health status, goal attainment, hospital readmission, and mortality. Among intervention participants, engagement with the mHealth-CR platform will be analyzed to understand the characteristics that determine different patterns of use (eg, persistent high engagement and declining engagement). Results As of December 2021, the RESILIENT trial had enrolled 116 participants. Enrollment is projected to continue until October 2023. The trial results are expected to be reported in 2024. Conclusions The RESILIENT trial will generate important evidence about the efficacy of mHealth-CR among older adults in multiple domains and characteristics that determine the sustained use of mHealth-CR. These findings will help design future precision medicine approaches to mobile health implementation in older adults. This knowledge is especially important in light of the COVID-19 pandemic that has shifted much of health care to a remote, internet-based setting. Trial Registration ClinicalTrials.gov NCT03978130; https://clinicaltrials.gov/ct2/show/NCT03978130 International Registered Report Identifier (IRRID) DERR1-10.2196/32163 

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4. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations

   https://doi.org/10.7554/eLife.81916  

   Sherratt, Katharine ; Gruson, Hugo ; Grah, Rok ; Johnson, Helen ; Niehus, Rene ; Prasse, Bastian ; Sandmann, Frank ; Deuschel, Jannik ; Wolffram, Daniel ; Abbott, Sam ; et al ( April 2023 , eLife)

   Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022.

   We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance.

   Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models.

   Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks.

   AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z).

    

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5. Predictive Models of Mortality for Hospitalized Patients With COVID-19: Retrospective Cohort Study

   https://doi.org/10.2196/21788  

   Wang, Taiyao ; Paschalidis, Aris ; Liu, Quanying ; Liu, Yingxia ; Yuan, Ye ; Paschalidis, Ioannis Ch ( January 2020 , JMIR Medical Informatics)

   null (Ed.)

   Background The novel coronavirus SARS-CoV-2 and its associated disease, COVID-19, have caused worldwide disruption, leading countries to take drastic measures to address the progression of the disease. As SARS-CoV-2 continues to spread, hospitals are struggling to allocate resources to patients who are most at risk. In this context, it has become important to develop models that can accurately predict the severity of infection of hospitalized patients to help guide triage, planning, and resource allocation. Objective The aim of this study was to develop accurate models to predict the mortality of hospitalized patients with COVID-19 using basic demographics and easily obtainable laboratory data. Methods We performed a retrospective study of 375 hospitalized patients with COVID-19 in Wuhan, China. The patients were randomly split into derivation and validation cohorts. Regularized logistic regression and support vector machine classifiers were trained on the derivation cohort, and accuracy metrics (F1 scores) were computed on the validation cohort. Two types of models were developed: the first type used laboratory findings from the entire length of the patient’s hospital stay, and the second type used laboratory findings that were obtained no later than 12 hours after admission. The models were further validated on a multicenter external cohort of 542 patients. Results Of the 375 patients with COVID-19, 174 (46.4%) died of the infection. The study cohort was composed of 224/375 men (59.7%) and 151/375 women (40.3%), with a mean age of 58.83 years (SD 16.46). The models developed using data from throughout the patients’ length of stay demonstrated accuracies as high as 97%, whereas the models with admission laboratory variables possessed accuracies of up to 93%. The latter models predicted patient outcomes an average of 11.5 days in advance. Key variables such as lactate dehydrogenase, high-sensitivity C-reactive protein, and percentage of lymphocytes in the blood were indicated by the models. In line with previous studies, age was also found to be an important variable in predicting mortality. In particular, the mean age of patients who survived COVID-19 infection (50.23 years, SD 15.02) was significantly lower than the mean age of patients who died of the infection (68.75 years, SD 11.83; P<.001). Conclusions Machine learning models can be successfully employed to accurately predict outcomes of patients with COVID-19. Our models achieved high accuracies and could predict outcomes more than one week in advance; this promising result suggests that these models can be highly useful for resource allocation in hospitals. 

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