Hospital trajectories and early predictors of clinical outcomes differ between SARS-CoV-2 and influenza pneumonia.

BACKGROUND: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients. METHODS: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of outcome were modelled using supervised machine learning classifiers. FINDINGS: Among 2,529 hospitalisations with SARS-CoV-2 and 2,256 with influenza pneumonia, the primary outcome occurred in 21% and 9%, respectively. Multi-state models differentiated oxygen requirement progression between viruses, with SARS-CoV-2 manifesting rapidly-escalating early hypoxemia. Highly contributory classifier variables for the primary outcome differed substantially between viruses. INTERPRETATION: SARS-CoV-2 and influenza pneumonia differ in presentation, hospital course, and outcome predictors. These pathogen-specific differential responses in viral pneumonias suggest distinct management approaches should be investigated. FUNDING: This project was supported by NIH/NCATS UL1 TR002345, NIH/NCATS KL2 TR002346 (PGL), the Doris Duke Charitable Foundation grant 2015215 (PGL), NIH/NHLBI R35 HL140026 (CSC), and a Big Ideas Award from the BJC HealthCare and Washington University School of Medicine Healthcare Innovation Lab and NIH/NIGMS R35 GM142992 (PS).

Predicting neurological outcomes after in-hospital cardiac arrests for patients with Coronavirus Disease 2019.

BACKGROUND: Machine learning models are more accurate than standard tools for predicting neurological outcomes in patients resuscitated after cardiac arrest. However, their accuracy in patients with Coronavirus Disease 2019 (COVID-19) is unknown. Therefore, we compared their performance in a cohort of cardiac arrest patients with COVID-19. METHODS: We conducted a retrospective analysis of resuscitation survivors in the Get With The Guidelines®-Resuscitation (GWTG-R) COVID-19 registry between February 2020 and May 2021. The primary outcome was a favorable neurological outcome, indicated by a discharge Cerebral Performance Category score ≤ 2. Pre- and peri-arrest variables were used as predictors. We applied our published logistic regression, neural network, and gradient boosted machine models developed in patients without COVID-19 to the COVID-19 cohort. We also updated the neural network model using transfer learning. Performance was compared between models and the Cardiac Arrest Survival Post-Resuscitation In-Hospital (CASPRI) score. RESULTS: Among the 4,125 patients with COVID-19 included in the analysis, 484 (12 %) patients survived with favorable neurological outcomes. The gradient boosted machine, trained on non-COVID-19 patients was the best performing model for predicting neurological outcomes in COVID-19 patients, significantly better than the CASPRI score (c-statistic: 0.75 vs 0.67, P < 0.001). While calibration improved for the neural network with transfer learning, it did not surpass the gradient boosted machine in terms of discrimination. CONCLUSION: Our gradient boosted machine model developed in non-COVID patients had high discrimination and adequate calibration in COVID-19 resuscitation survivors and may provide clinicians with important information for these patients.

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019. DESIGN: Retrospective observational study. SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS: All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

Identifying COVID-19 Outbreaks From Contact-Tracing Interview Forms for Public Health Departments: Development of a Natural Language Processing Pipeline.

BACKGROUND: In Wisconsin, COVID-19 case interview forms contain free-text fields that need to be mined to identify potential outbreaks for targeted policy making. We developed an automated pipeline to ingest the free text into a pretrained neural language model to identify businesses and facilities as outbreaks. OBJECTIVE: We aimed to examine the precision and recall of our natural language processing pipeline against existing outbreaks and potentially new clusters. METHODS: Data on cases of COVID-19 were extracted from the Wisconsin Electronic Disease Surveillance System (WEDSS) for Dane County between July 1, 2020, and June 30, 2021. Features from the case interview forms were fed into a Bidirectional Encoder Representations from Transformers (BERT) model that was fine-tuned for named entity recognition (NER). We also developed a novel location-mapping tool to provide addresses for relevant NER. Precision and recall were measured against manually verified outbreaks and valid addresses in WEDSS. RESULTS: There were 46,798 cases of COVID-19, with 4,183,273 total BERT tokens and 15,051 unique tokens. The recall and precision of the NER tool were 0.67 (95% CI 0.66-0.68) and 0.55 (95% CI 0.54-0.57), respectively. For the location-mapping tool, the recall and precision were 0.93 (95% CI 0.92-0.95) and 0.93 (95% CI 0.92-0.95), respectively. Across monthly intervals, the NER tool identified more potential clusters than were verified in WEDSS. CONCLUSIONS: We developed a novel pipeline of tools that identified existing outbreaks and novel clusters with associated addresses. Our pipeline ingests data from a statewide database and may be deployed to assist local health departments for targeted interventions.

Endotracheal Tube Size Is Associated With Mortality in Patients With Status Asthmaticus.

BACKGROUND: There is limited evidence on the clinical importance of the endotracheal tube (ETT) size selection in patients with status asthmaticus who require invasive mechanical ventilation. We set out to explore the clinical outcomes of different ETT internal diameter sizes in subjects mechanically ventilated with status asthmaticus. METHODS: This was a retrospective study of intubated and non-intubated adults admitted for status asthmaticus between 2014-2021. We examined in-hospital mortality across subgroups with different ETT sizes, as well as non-intubated subjects, using logistic and generalized linear mixed-effects models. We adjusted for demographics, Charlson comorbidities, the first Sequential Organ Failure Assessment score, intubating personnel and setting, COVID-19, and the first PaCO2 . Finally, we calculated the post-estimation predictions of mortality. RESULTS: We enrolled subjects from 964 status asthmaticus admissions. The average age was 46.9 (SD 14.5) y; 63.5% of the encounters were women and 80.6% were Black. Approximately 72% of subjects (690) were not intubated. Twenty-eight percent (275) required endotracheal intubation, of which 3.3% (32) had a 7.0 mm or smaller ETT (ETT ≤ 7 group), 16.5% (159) a 7.5 mm ETT (ETT ≤ 7.5 group), and 8.6% (83) an 8.0 mm or larger ETT (ETT ≥ 8 group). The adjusted mortality was 26.7% (95% CI 13.2-40.2) for the ETT ≤ 7 group versus 14.3% ([(95% CI 6.9-21.7%], P = .04) for ETT ≤ 7.5 group and 11.0% ([95% CI 4.4-17.5], P = .02) for ETT ≥ 8 group, respectively. CONCLUSIONS: Intubated subjects with status asthmaticus had higher mortality than non-intubated subjects. Intubated subjects had incrementally higher observed mortality with smaller ETT sizes. Physiologic mechanisms can support this dose-response relationship.

Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN: This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING: Sixty-eight U.S. ICUs. PATIENTS: Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS: eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

The impact of vaccination to control COVID-19 burden in the United States: A simulation modeling approach.

INTRODUCTION: Vaccination programs aim to control the COVID-19 pandemic. However, the relative impacts of vaccine coverage, effectiveness, and capacity in the context of nonpharmaceutical interventions such as mask use and physical distancing on the spread of SARS-CoV-2 are unclear. Our objective was to examine the impact of vaccination on the control of SARS-CoV-2 using our previously developed agent-based simulation model. METHODS: We applied our agent-based model to replicate COVID-19-related events in 1) Dane County, Wisconsin; 2) Milwaukee metropolitan area, Wisconsin; 3) New York City (NYC). We evaluated the impact of vaccination considering the proportion of the population vaccinated, probability that a vaccinated individual gains immunity, vaccination capacity, and adherence to nonpharmaceutical interventions. We estimated the timing of pandemic control, defined as the date after which only a small number of new cases occur. RESULTS: The timing of pandemic control depends highly on vaccination coverage, effectiveness, and adherence to nonpharmaceutical interventions. In Dane County and Milwaukee, if 50% of the population is vaccinated with a daily vaccination capacity of 0.25% of the population, vaccine effectiveness of 90%, and the adherence to nonpharmaceutical interventions is 60%, controlled spread could be achieved by June 2021 versus October 2021 in Dane County and November 2021 in Milwaukee without vaccine. DISCUSSION: In controlling the spread of SARS-CoV-2, the impact of vaccination varies widely depending not only on effectiveness and coverage, but also concurrent adherence to nonpharmaceutical interventions.

Hospital-Level Variation in Death for Critically Ill Patients with COVID-19.

RATIONALE: Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear. OBJECTIVE: Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability. METHODS: In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models. MEASUREMENTS AND MAIN RESULTS: A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%). CONCLUSION: There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States : A Simulation Modeling Approach.

BACKGROUND: Across the United States, various social distancing measures were implemented to control the spread of coronavirus disease 2019 (COVID-19). However, the effectiveness of such measures for specific regions with varying population demographic characteristics and different levels of adherence to social distancing is uncertain. OBJECTIVE: To determine the effect of social distancing measures in unique regions. DESIGN: An agent-based simulation model. SETTING: Agent-based model applied to Dane County, Wisconsin; the Milwaukee metropolitan (metro) area; and New York City (NYC). PATIENTS: Synthetic population at different ages. INTERVENTION: Different times for implementing and easing social distancing measures at different levels of adherence. MEASUREMENTS: The model represented the social network and interactions among persons in a region, considering population demographic characteristics, limited testing availability, "imported" infections, asymptomatic disease transmission, and age-specific adherence to social distancing measures. The primary outcome was the total number of confirmed COVID-19 cases. RESULTS: The timing of and adherence to social distancing had a major effect on COVID-19 occurrence. In NYC, implementing social distancing measures 1 week earlier would have reduced the total number of confirmed cases from 203 261 to 41 366 as of 31 May 2020, whereas a 1-week delay could have increased the number of confirmed cases to 1 407 600. A delay in implementation had a differential effect on the number of cases in the Milwaukee metro area versus Dane County, indicating that the effect of social distancing measures varies even within the same state. LIMITATION: The effect of weather conditions on transmission dynamics was not considered. CONCLUSION: The timing of implementing and easing social distancing measures has major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach.

BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases.