The Burden of Incidental Sars-cov-2 Infections in Hospitalized Patients Across Pandemic Waves in Canada (preprint)

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being “for COVID-19” (due to direct manifestations of SARS-CoV-2 infection) versus being an “incidental” finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with “incidental” SARS-CoV-2 infection are less of a burden to patients and the healthcare system.  Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the “Direct” cause for the hospitalization (70%), (ii) a potential “Contributing” factor for the hospitalization (4%), or (iii) an “Incidental” finding that did not influence the need for admission (26%).  The proportion of incidental SARS-CoV-2 infections rose fro 10% in Wave 1 to 41% during the Omicron wave.  Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%), compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

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.

Diagnostic Yield of Screening for SARS-CoV-2 among Patients Admitted for Alternate Diagnoses (preprint)

ObjectivesTo determine the diagnostic yield of screening patients for SARS-CoV-2 who were admitted with a diagnosis unrelated to COVID-19, and identify risk factors for positive tests. DesignCohort from the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry Setting30 acute care hospitals across Canada ParticipantsPatients hospitalized for non-COVID-19 related diagnoses who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 1, and December 29, 2020 Main outcomePositive nucleic acid amplification test (NAAT) for SARS-CoV-2 Outcome measureDiagnostic yield ResultsWe enrolled 15,690 consecutive eligible adults who were admitted to hospital without clinically suspected COVID-19. Among these patients, 122 tested positive for COVID-19, resulting in a diagnostic yield of 0.8% (95% CI 0.64% - 0.92%). Factors associated with a positive test included presence of a fever, being a healthcare worker, having a positive household contact or institutional exposure, and living in an area with higher 7-day average incident COVID-19 cases. ConclusionsUniversal screening of hospitalized patients for COVID-19 across two pandemic waves had a low diagnostic yield and should be informed by individual-level risk assessment in addition to regional COVID-19 prevalence. Trial registrationNCT04702945 SUMMARY BOXESSection 1: Universal screening of admitted patients for SARS-CoV-2 was implemented in many hospitals at the beginning of the pandemic. The Infections Diseases Society of America (IDSA) recommended avoiding universal screening of asymptomatic hospitalized patients in areas and times of low-COVID prevalence (defined as <2% prevalence) with very low certainty of evidence, based on studies of COVID-19 prevalence among asymptomatic individuals in the community. Section 2: This study supports IDSA recommendations to avoid universal screening for COVID-19 in times and areas of low COVID prevalence and identifies patient-level risk factors strongly associated with positive testing that should be considered for screening.

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.

DERIVATION AND VALIDATION OF A CLINICAL SCORE TO PREDICT DEATH AMONG NON-PALLIATIVE COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS: THE CCEDRRN COVID MORTALITY SCORE (preprint)

BackgroundPredicting mortality from coronavirus disease 2019 (COVID-19) using information available when patients present to the Emergency Department (ED) can inform goals-of-care decisions and assist with ethical allocation of critical care resources. MethodsWe conducted an observational study to develop and validate a clinical score to predict ED and in-hospital mortality among consecutive non-palliative COVID-19 patients. We recruited from 44 hospitals participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1, 2020 and January 31, 2021. We randomly assigned hospitals to derivation or validation, and pre-specified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort, and examined its performance in predicting ED and in-hospital mortality in a validation cohort. ResultsOf 8,761 eligible patients, 618 (7{middle dot}01%) died. The score included age, sex, type of residence, arrival mode, chest pain, severe liver disease, respiratory rate, and level of respiratory support. The area under the curve was 0{middle dot}92 (95% confidence intervals [CI] 0{middle dot}91-0{middle dot}93) in derivation and 0{middle dot}92 (95%CI 0{middle dot}89-0{middle dot}93) in validation. The score had excellent calibration. Above a score of 15, the observed mortality was 81{middle dot}0% (81/100) with a specificity of 98{middle dot}8% (95%CI 99{middle dot}5-99{middle dot}9%). InterpretationThe CCEDRRN COVID Mortality Score is a simple score that accurately predicts mortality with variables that are available on patient arrival without the need for diagnostic tests. Trial registrationClinicaltrials.gov, NCT04702945

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.