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Heterogeneity has been observed in outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19). Identification of clinical phenotypes may facilitate tailored therapy and improve outcomes. The purpose of this study is to identify specific clinical phenotypes across COVID-19 patients and compare admission characteristics and outcomes. This is a retrospective analysis of COVID-19 patients from March 7, 2020 to August 25, 2020 at 14 U.S. hospitals. Ensemble clustering was performed on 33 variables collected within 72 hours of admission. Principal component analysis was performed to visualize variable contributions to clustering. Multinomial regression models were fit to compare patient comorbidities across phenotypes. Multivariable models were fit to estimate associations between phenotype and in-hospital complications and clinical outcomes. The database included 1,022 hospitalized patients with COVID-19. Three clinical phenotypes were identified (I, II, III), with 236 [23.1%] patients in phenotype I, 613 [60%] patients in phenotype II, and 173 [16.9%] patients in phenotype III. Patients with respiratory comorbidities were most commonly phenotype III (p = 0.002), while patients with hematologic, renal, and cardiac (all p<0.001) comorbidities were most commonly phenotype I. Adjusted odds of respiratory, renal, hepatic, metabolic (all p<0.001), and hematological (p = 0.02) complications were highest for phenotype I. Phenotypes I and II were associated with 7.30-fold (HR:7.30, 95% CI:(3.11-17.17), p<0.001) and 2.57-fold (HR:2.57, 95% CI:(1.10-6.00), p = 0.03) increases in hazard of death relative to phenotype III. We identified three clinical COVID-19 phenotypes, reflecting patient populations with different comorbidities, complications, and clinical outcomes. Future research is needed to determine the utility of these phenotypes in clinical practice and trial design.

Patient symptoms, crucial for disease progression and diagnosis, are often captured in unstructured clinical notes. Large language models (LLMs) offer potential advantages in extracting patient symptoms compared to traditional rule-based information extraction (IE) systems. This study compared fine-tuned LLMs (LLaMA2-13B and LLaMA3-8B) against BioMedICUS, a rule-based IE system, for extracting symptoms related to acute and post-acute sequelae of SARS-CoV-2 from clinical notes. The study utilized three corpora: UMN-COVID, UMN-PASC, and N3C-COVID. Prevalence, keyword and fairness analyses were conducted to assess symptom distribution and model equity across demographics. BioMedICUS outperformed fine-tuned LLMs in most cases. On the UMN PASC dataset, BioMedICUS achieved a macro-averaged F1-score of 0.70 for positive mention detection, compared to 0.66 for LLaMA2-13B and 0.62 for LLaMA3-8B. For the N3C COVID dataset, BioMedICUS scored 0.75, while LLaMA2-13B and LLaMA3-8B scored 0.53 and 0.68, respectively for positive mention detection. However, LLMs performed better in specific instances, such as detecting positive mentions of change in sleep in the UMN PASC dataset, where LLaMA2-13B (0.79) and LLaMA3-8B (0.65) outperformed BioMedICUS (0.60). For fairness analysis, BioMedICUS generally showed stronger performance across patient demographics. Keyword analysis using ANOVA on symptom distributions across all three corpora showed that both corpus (df = 2, p < 0.001) and symptom (df = 79, p < 0.001) have a statistically significant effect on log-transformed term frequency-inverse document frequency (TF-IDF) values such that corpus accounts for 52% of the variance in log_tfidf values and symptom accounts for 35%. While BioMedICUS generally outperformed the LLMs, the latter showed promising results in specific areas, particularly LLaMA3-8B, in identifying negative symptom mentions. However, both LLaMA models faced challenges in demographic fairness and generalizability. These findings underscore the need for diverse, high-quality training datasets and robust annotation processes to enhance LLMs' performance and reliability in clinical applications.

In this trial involving overweight or obese outpatients with Covid-19, investigators found that none of three repurposed drugs (metformin, ivermectin, and fluvoxamine) reduced the risk of serious disease.

The SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition. Characterization of disposition associated factors following SARS-CoV-2. Retrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization. Midwest academic health-system. Patients above the age 18 years admitted with PCR + SARS-CoV-2. None. Discharge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH). We identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH). Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6-85.1) compared to those discharged home (57.0 years, IQR: 38.2-69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9). Older age (RRR:1.04, 95% CI:1.041-1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168-1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060-1.077) and higher EI (RRR:1.09, 95% CI:1.071-1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47-0.88), (RRR 0.48 CI 0.34-0.67) and (RRR 0.586 CI 0.352-0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444-780). The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99-0.99) and albumin levels 0.342 (CI 0.26-0.45), and higher with increased CRP (RRR 1.006 CI 1.004-1.007) and D-Dimer (RRR 1.070 CI 1.039-1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497-0.798. An increase in D-Dimer (RRR1.033 CI 1.002-1.064) and CRP (RRR1.002 CI1.001-1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC. Older age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH.

To prospectively evaluate a logistic regression-based machine learning (ML) prognostic algorithm implemented in real-time as a clinical decision support (CDS) system for symptomatic persons under investigation (PUI) for Coronavirus disease 2019 (COVID-19) in the emergency department (ED). We developed in a 12-hospital system a model using training and validation followed by a real-time assessment. The LASSO guided feature selection included demographics, comorbidities, home medications, vital signs. We constructed a logistic regression-based ML algorithm to predict \"severe\" COVID-19, defined as patients requiring intensive care unit (ICU) admission, invasive mechanical ventilation, or died in or out-of-hospital. Training data included 1,469 adult patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within 14 days of acute care. We performed: 1) temporal validation in 414 SARS-CoV-2 positive patients, 2) validation in a PUI set of 13,271 patients with symptomatic SARS-CoV-2 test during an acute care visit, and 3) real-time validation in 2,174 ED patients with PUI test or positive SARS-CoV-2 result. Subgroup analysis was conducted across race and gender to ensure equity in performance. The algorithm performed well on pre-implementation validations for predicting COVID-19 severity: 1) the temporal validation had an area under the receiver operating characteristic (AUROC) of 0.87 (95%-CI: 0.83, 0.91); 2) validation in the PUI population had an AUROC of 0.82 (95%-CI: 0.81, 0.83). The ED CDS system performed well in real-time with an AUROC of 0.85 (95%-CI, 0.83, 0.87). Zero patients in the lowest quintile developed \"severe\" COVID-19. Patients in the highest quintile developed \"severe\" COVID-19 in 33.2% of cases. The models performed without significant differences between genders and among race/ethnicities (all p-values > 0.05). A logistic regression model-based ML-enabled CDS can be developed, validated, and implemented with high performance across multiple hospitals while being equitable and maintaining performance in real-time validation.

Background Arrhythmias are common in critically ill patients, though the impact of arrhythmias on surgical patients is not well delineated. We aimed to characterize mortality following arrhythmias in critically ill patients. Methods We performed a propensity-matched retrospective analysis of intensive care unit (ICU) patients from 2007 to 2017 in the Cerner Acute Physiology and Chronic Health Evaluation database. We compared outcomes between patients with and without arrhythmias and those with and without surgical indications for ICU admission. We also modeled predictors of arrhythmias in surgical patients. Results 467,951 patients were included; 97,958 (20.9%) were surgical patients. Arrhythmias occurred in 1.4% of the study cohorts. Predictors of arrhythmias in surgical patients included a history of cardiovascular disease (odds ratio [OR] 1.35, 95% confidence interval [CI95] 1.11–1.63), respiratory failure (OR 1.48, CI95 1.12–1.96), pneumonia (OR 3.17, CI95 1.98–5.10), higher bicarbonate level (OR 1.03, CI95 1.01–1.05), lower albumin level (OR 0.79, CI95 0.68–0.91), and vasopressor requirement (OR 27.2, CI95 22.0–33.7). After propensity matching, surgical patients with arrhythmias had a 42% mortality risk reduction compared to non-surgical patients (risk ratio [RR] 0.58, CI 95 0.43–0.79). Predicted probabilities of mortality for surgical patients were lower at all ages. Conclusions Surgical patients with arrhythmias are at lower risk of mortality than non-surgical patients. In this propensity-matched analysis, predictors of arrhythmias in critically ill surgical patients included a history of cardiovascular disease, respiratory complications, increased bicarbonate levels, decreased albumin levels, and vasopressor requirement. These findings highlight the differential effect of arrhythmias on different cohorts of critically ill populations.

BackgroundDespite past and ongoing efforts to achieve health equity in the USA, racial and ethnic disparities persist and appear to be exacerbated by COVID-19.ObjectiveEvaluate neighborhood-level deprivation and English language proficiency effect on disproportionate outcomes seen in racial and ethnic minorities diagnosed with COVID-19.DesignRetrospective cohort studySettingHealth records of 12 Midwest hospitals and 60 clinics in Minnesota between March 4, 2020, and August 19, 2020PatientsPolymerase chain reaction–positive COVID-19 patientsExposuresArea Deprivation Index (ADI) and primary languageMain MeasuresThe primary outcome was COVID-19 severity, using hospitalization within 45 days of diagnosis as a marker of severity. Logistic and competing-risk regression models assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race, effects of ADI and primary language were measured using logistic regression.ResultsA total of 5577 individuals infected with SARS-CoV-2 were included; 866 (n = 15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p < 0.001) and more likely to be male (n = 425 [49.1%] vs. 2049 [43.5%], p = 0.002). Of those requiring hospitalization, 43.9% (n = 381), 19.9% (n = 172), 18.6% (n = 161), and 11.8% (n = 102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity: Hispanic patients (OR 3.8, 95% CI 2.72–5.30), Asians (OR 2.39, 95% CI 1.74–3.29), and Blacks (OR 1.50, 95% CI 1.15–1.94). ADI was not associated with hospitalization. Non-English-speaking (OR 1.91, 95% CI 1.51–2.43) significantly increased odds of hospital admission across and within minority groups.ConclusionsMinority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the ongoing need to determine the mechanisms that contribute to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity among minority groups.

Circulating tumor cells (CTCs) are cells shed from solid tumors into circulation and have been shown to be prognostic in the setting of metastatic disease. These cells are obtained through a routine blood draw and may serve as an easily accessible marker for monitoring treatment effectiveness. Because of the rapid progression of pancreatic ductal adenocarcinoma (PDAC), early insight into treatment effectiveness may allow for necessary and timely changes in treatment regimens. The objective of this study was to evaluate CTC burden as a biomarker of response to treatment with a oral phosphatidylinositol-3-kinase inhibitor, BKM120, in patient-derived xenograft (PDX) mouse models of PDAC. PDX mice were randomized to receive vehicle or BKM120 treatment for 28 days and CTCs were enumerated from whole blood before and after treatment using a microfluidic chip that selected for EpCAM (epithelial cell adhesion molecule) positive cells. This microfluidic device allowed for the release of captured CTCs and enumeration of these cells via their electrical impedance signatures. Median CTC counts significantly decreased in the BKM120 group from pre- to post-treatment (26.61 to 2.21 CTCs/250 µL, p = 0.0207) while no significant change was observed in the vehicle group (23.26 to 11.89 CTCs/250 µL, p = 0.8081). This reduction in CTC burden in the treatment group correlated with tumor growth inhibition indicating CTC burden is a promising biomarker of response to treatment in preclinical models. Mutant enriched sequencing of isolated CTCs confirmed that they harbored KRAS G12V mutations, identical to the matched tumors. In the long-term, PDX mice are a useful preclinical model for furthering our understanding of CTCs. Clinically, mutational analysis of CTCs and serial monitoring of CTC burden may be used as a minimally invasive approach to predict and monitor treatment response to guide therapeutic regimens.