Diagnostic accuracy of age-adjusted D-dimer for pulmonary embolism among Emergency Department patients with suspected SARS-COV-2: A Canadian COVID-19 Emergency Department Rapid Response Network study (preprint)

Importance: Ruling out pulmonary embolism (PE) among patients presenting to the Emergency Department (ED) with suspected or confirmed SARS-COV-2 is challenging due to symptom overlap, known increased pro-thrombotic risk, and unclear D-dimer test interpretation. Objective: Our primary objective was to assess the diagnostic accuracy of standard and age-adjusted D-dimer test thresholds for predicting 30-day pulmonary embolism (PE) diagnosis in patients with suspected SARS-COV-2 infection. Design, Setting, and Participants: This was a retrospective observational study using data from 50 sites enrolling patients into the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry between March 1, 2020 to July 2, 2021. Adults ([≥]18 years) with SARS-COV-2 testing performed at index ED visit were included if they had any of the following presenting complaints: chest pain, shortness of breath, hypoxia, syncope/presyncope, or hemoptysis. We excluded patients with duplicate records or no valid provincial healthcare number. Main Outcomes and Measures: Our primary end point was 30-day PE diagnosis based on a positive computed tomography pulmonary angiogram (CTPA) or hospital discharge diagnosis code of PE. The outcome measure was the diagnostic accuracy of an age adjusted D-dimer strategy as compared to absolute D-dimer thresholds (500 - 5000 ng/mL). Results: 52,038 patients met inclusion criteria. Age-adjusted D-dimer had a sensitivity (SN) of 96% (95% CI 93-98%) and a specificity (SP) of 48% (95% CI 48-49%) which was comparable to the most sensitive absolute threshold of 500 ng/mL (SN 98%, 95% CI 96-99%; SP 41%, 95% CI 40-42%). Other absolute D-dimer thresholds did not perform well enough for clinical reliability (SN <90%). Both age-adjusted and absolute D-dimer performed better in SARS-COV-2 negative patients as compared to SARS-COV-2 positive patients for predicting 30-day PE diagnosis (c-statistic 0.88 vs 0.80). Conclusions and Relevance: In this large Canadian cohort of ED patients with suspected SARS-COV-2 infection, an age-adjusted D-dimer strategy had similar sensitivity and superior specificity to the most sensitive D-dimer threshold of 500 ng/mL for predicting 30-day PE diagnosis irrespective of SARS-COV-2 infection status. Adopting an age-adjusted D-dimer strategy in patients with suspected SARS-COV-2 may help avoid unnecessary CTPA testing without compromising safety.

TREATMENTS, RESOURCE UTILIZATION, AND OUTCOMES OF COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS ACROSS PANDEMIC WAVES: AN OBSERVATIONAL STUDY BY THE CANADIAN COVID-19 EMERGENCY DEPARTMENT RAPID RESPONSE NETWORK (CCEDRRN) (preprint)

Background: Treatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves. Methods: This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes. Results: We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 -- 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 -- 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 -- 0.8) and critical care admission (OR 0.6; 95%CI 0.4 -- 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4). Interpretation: In patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave.

Development and validation of a clinical risk score to predict SARS-CoV-2 infection in emergency department patients: The CCEDRRN COVID-19 Infection Score (CCIS) (preprint)

ObjectivesTo develop and validate a clinical risk score that can accurately quantify an emergency department patients probability of SARS-CoV-2 infection without the need for laboratory testing DesignCohort study of participants in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. Regression models were fitted to predict a positive SARS-CoV-2 test result using clinical and demographic predictors, as well as an indicator of local SARS-CoV-2 incidence. Setting32 emergency departments in eight Canadian provinces Participants27,665 consecutively-enrolled patients who were tested for SARS-CoV-2 in participating emergency departments between March 1-October 30,2020 Main outcome measuresPositive SARS-CoV-2 nucleic acid test result within 14 days of an index emergency department encounter for suspected COVID-19 disease ResultsWe derived a 10-item CCEDRRN COVID-19 Infection Score using data from 21,743 patients. This score included variables from history and physical examination, and an indicator of local disease incidence. The score had a c-statistic of 0.838 with excellent calibration. We externally validated the rule in 5,295 patients. The score maintained excellent discrimination and calibration, and had superior performance compared to another previously published risk score. Score cutoffs were identified that can rule-in or rule-out SARS-CoV-2 infection without the need for nucleic acid testing with 97.4 % sensitivity (95% CI 96.4-98..3) and 95.9% specificity (95% CI 95.5-96.0). ConclusionsThe CCEDRRN COVID-19 Infection Score uses clinical characteristics and publicly available indicators of disease incidence to quantify a patients probability of SARS-CoV-2 infection. The score can identify patients at sufficiently high risk of SARS-CoV-2 infection to warrant isolation and empiric therapy prior to test confirmation, while also identifying patients at sufficiently low risk of infection that they may not need testing. Trial registrationCCEDRRN is registered at clinicaltrials.gov (NCT04702945). FundingThe network is funded by the Canadian Institutes of Health Research (447679), BC Academic Health Science Network Society, BioTalent Canada, Genome BC (COV024; VAC007), Ontario Ministry of Colleges and Universities (C-655-2129), the Saskatchewan Health Research Foundation (5357) and the Fondation CHU de Quebec (Octroi #4007). These organizations are not-for-profit, and had no role in study conduct, analysis, or manuscript preparation.