Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19.

Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. DESIGN: Retrospective, observational cohort study. SETTING: ICUs at two large, urban, academic referral hospitals. PATIENTS: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (ß = 0.30; se, 0.07; p ≤ 0.01). CONCLUSIONS: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19

OBJECTIVES: Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. DESIGN: Retrospective, observational cohort study. SETTING: ICUs at two large, urban, academic referral hospitals. PATIENTS: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57;95% CI, 1.17–2.12;p < 0.01) and ferritin quartiles (OR, 1.36;95% CI, 1.02–1.81;p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49;95% CI, 1.14–1.94;p < 0.01) and coma independently (OR, 1.52;95% CI, 1.08–2.14;p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33;95% CI, 1.04–1.70;p = 0.026) and coma independently (OR, 1.59;95% CI, 1.14–2.23;p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36;95% CI, 1.03–1.79;p = 0.030) and delirium severity the next day (β = 0.30;se, 0.07;p ≤ 0.01). CONCLUSIONS: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.

The Effect of In-Person Primary and Secondary School Instruction on County-Level Severe Acute Respiratory Syndrome Coronavirus 2 Spread in Indiana.

BACKGROUND: Our goal was to determine the county-level effect of in-person primary and secondary school reopening on daily cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Indiana. METHODS: In this county-level, population-based study, we used a panel data regression analysis of the proportion of in-person learning to evaluate an association with community-wide daily new SARS-CoV-2 cases. The study period was 12 July 2020-6 October 2020. We included 73 of 92 (79.3%) Indiana counties in the analysis, accounting for 85.7% of school corporations and 90.6% of student enrollment statewide. The primary exposure was the proportion of students returning to in-person instruction. The primary outcome was the daily new SARS-CoV-2 cases per 100 000 residents at the county level. RESULTS: There is a statistically significant relationship between the proportion of students attending K-12 schools in-person and the county level daily cases of SARS-CoV-2 28 days later. For all ages, the coefficient of interest (ß) is estimated at 3.36 (95% confidence interval, 1.91 to 4.81; P < .001). This coefficient represents the effect of a change in the proportion of students attending in-person on new daily cases 28 days later. For example, a 10 percentage point increase in K-12 students attending school in-person is associated with a daily increase in SARS-CoV-2 cases in the county equal to 0.336 cases/100 000 residents of all ages. CONCLUSIONS: In-person primary and secondary school is associated with a statistically significant but proportionally small increase in the spread of SARS-CoV-2 cases.

Predicting COVID-19-Related Health Care Resource Utilization Across a Statewide Patient Population: Model Development Study.

BACKGROUND: The COVID-19 pandemic has highlighted the inability of health systems to leverage existing system infrastructure in order to rapidly develop and apply broad analytical tools that could inform state- and national-level policymaking, as well as patient care delivery in hospital settings. The COVID-19 pandemic has also led to highlighted systemic disparities in health outcomes and access to care based on race or ethnicity, gender, income-level, and urban-rural divide. Although the United States seems to be recovering from the COVID-19 pandemic owing to widespread vaccination efforts and increased public awareness, there is an urgent need to address the aforementioned challenges. OBJECTIVE: This study aims to inform the feasibility of leveraging broad, statewide datasets for population health-driven decision-making by developing robust analytical models that predict COVID-19-related health care resource utilization across patients served by Indiana's statewide Health Information Exchange. METHODS: We leveraged comprehensive datasets obtained from the Indiana Network for Patient Care to train decision forest-based models that can predict patient-level need of health care resource utilization. To assess these models for potential biases, we tested model performance against subpopulations stratified by age, race or ethnicity, gender, and residence (urban vs rural). RESULTS: For model development, we identified a cohort of 96,026 patients from across 957 zip codes in Indiana, United States. We trained the decision models that predicted health care resource utilization by using approximately 100 of the most impactful features from a total of 1172 features created. Each model and stratified subpopulation under test reported precision scores >70%, accuracy and area under the receiver operating curve scores >80%, and sensitivity scores approximately >90%. We noted statistically significant variations in model performance across stratified subpopulations identified by age, race or ethnicity, gender, and residence (urban vs rural). CONCLUSIONS: This study presents the possibility of developing decision models capable of predicting patient-level health care resource utilization across a broad, statewide region with considerable predictive performance. However, our models present statistically significant variations in performance across stratified subpopulations of interest. Further efforts are necessary to identify root causes of these biases and to rectify them.

Can Salivary Innate Immune Molecules Provide Clue on Taste Dysfunction in COVID-19?

Emerging concerns following the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) pandemic are the long-term effects of coronavirus disease (COVID)-19. Dysgeusia in COVID-19 is supported by the abundant expression of the entry receptor, angiotensin-converting enzyme-2 (ACE2), in the oral mucosa. The invading virus perturbs the commensal biofilm and regulates the host responses that permit or suppress viral infection. We correlated the microbial recognition receptors and soluble ACE2 (sACE2) with the SARS-CoV2 measures in the saliva of COVID-19 patients. Data indicate that the toll-like receptor-4, peptidoglycan recognition protein, and sACE2 are elevated in COVID-19 saliva and correlate moderately with the viral load.

Delirium Incidence, Duration, and Severity in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: To determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019. DESIGN: Retrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU. SETTING: Two large, academic centers serving the state of Indiana. PATIENTS: Consecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years (sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13-25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4-11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5-7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1-22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality. CONCLUSIONS: Delirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus' neurologic effects is needed for patients with coronavirus disease 2019.

Mortality Rates in a Diverse Cohort of Mechanically Ventilated Patients With Novel Coronavirus in the Urban Midwest.

OBJECTIVES: Differences in mortality rates previously reported in critically ill patients with coronavirus disease 2019 have increased the need for additional data on mortality and risk factors for death. We conducted this study to describe length of stay, mortality, and risk factors associated with in-hospital mortality in mechanically ventilated patients with coronavirus disease 2019. DESIGN: Observational study. SETTING: Two urban, academic referral hospitals in Indianapolis, Indiana. PATIENTS OR SUBJECTS: Participants were critically ill patients 18 years old and older, admitted with coronavirus disease 2019 between March 1, 2020, and April 27, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included in-hospital mortality, duration of mechanical ventilation, and length of stay. A total of 242 patients were included with mean age of 59.6 years (sd, 15.5 yr), 41.7% female and 45% African American. Mortality in the overall cohort was 19.8% and 20.5% in the mechanically ventilated subset. Patients who died were older compared with those that survived (deceased: mean age, 72.8 yr [sd, 10.6 yr] vs patients discharged alive: 54.3 yr [sd, 14.8 yr]; p < 0.001 vs still hospitalized: 59.5 yr [sd, 14.4 yr]; p < 0.001) and had more comorbidities compared with those that survived (deceased: 2 [0.5-3] vs survived: 1 [interquartile range, 0-1]; p = 0.001 vs still hospitalized: 1 [interquartile range, 0-2]; p = 0.015). Older age and end-stage renal disease were associated with increased hazard of in-hospital mortality: age 65-74 years (hazard ratio, 3.1 yr; 95% CI, 1.2-7.9 yr), age 75+ (hazard ratio, 4.1 yr; 95% CI, 1.6-10.5 yr), and end-stage renal disease (hazard ratio, 5.9 yr; 95% CI, 1.3-26.9 yr). The overall median duration of mechanical ventilation was 9.3 days (interquartile range, 5.7-13.7 d), and median ICU length of stay in those that died was 8.7 days (interquartile range, 4.0-14.9 d), compared with 9.2 days (interquartile range, 4.0-14.0 d) in those discharged alive, and 12.7 days (interquartile range, 7.2-20.3 d) in those still remaining hospitalized.Conclusions:: We found mortality rates in mechanically ventilated patients with coronavirus disease 2019 to be lower than some previously reported with longer lengths of stay.

Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation.

OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). D-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if D-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if D-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. D-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.