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.

PCR to CRISPR: Role of Nucleic Acid Tests (NAT) in detection of COVID-19.

COVID-19 infection has emerged as an unparalleled pandemic with morbidity and mortality tolls challenging diagnostic approaches and therapeutic interventions, and raising serious questions for healthcare policy-makers. From the diagnostic perspective, Reverse transcriptase polymerase chain reaction remains the gold standard. However, issues associated with gene primer variation in different countries, low analytical sensitivity, cross-reactivity with certain human coronaviruses have raised serious concerns within the scientific community. Alongside longer turnaround times, requirements of sophisticated equipment and trained technicians are the other challenges for conventional reverse transcriptase polymerase chain reaction testing. The recent biotechnological boom has now allowed newer nucleic acid testing options for diagnosing severe acute respiratory syndrome Coronovairus 2 (SARS-CoV2) with much better diagnostic efficiency, reduced turnaround times and possible benefit for use as a point-of-care test. Isothermal techniques with simple equipment requirements along with uniform temperature for analysis have emerged to be more sensitive and specific with turnaround times as low as 10-15 minutes. Similarly, Cluster Regularly Interspaced Short Palindromic Repeats have also been seen to play a very decisive role in COVID-19 diagnostics with much superior diagnostic efficiency and feasibility as a point-of-care test and its possible use for sequencing. The current narrative review was planned to consolidate data for all possible nucleic acid testing options under research/clinical use, and to provide a comparative assessment from the perspective of both the clinician and the laboratory.

Venous thromboembolism in patients with COVID-19 infection: risk factors, prevention, and management.

Venous thromboembolic complications have emerged as serious sequelae in COVID-19 infections. This article summarizes the most current information regarding pathophysiology, risk factors and hematologic markers, incidence and timing of events, atypical venous thromboembolic complications, prophylaxis recommendations, and therapeutic recommendations. Data will likely to continue to rapidly evolve as more knowledge is gained regarding venous events in COVID-19 patients.

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.

Review of evidence on using ACEi and ARBs in patients with hypertension and COVID-19.

COVID-19 has recently become a major pandemic with associated socioeconomic dimensions. Mortality statistics suggest that COVID-19 is more lethal in aged patients with comorbid conditions including hypertension. There is ongoing debate about whether the use of angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are useful or hazardous in patients with COVID-19, with both narratives supported by researchers with different hypotheses. The researchers supporting the use of these medications believe ACE2 functional blockers may block cellular entry of the SARS-CoV-2 virus and thus improve patient outcomes. The counter viewpoint argues that continuous use of these drugs results in hyperexpression of ACE2 receptors on respiratory epithelium allowing easier SARS-CoV-2 intracellular entry, resulting in enhanced viral replication and tissue damage. This short review discusses the available research on the subject with the objective to consolidate data to allow formulation of recommendations on their use or otherwise. Moreover, the authors also suggest areas for future research on the subject.