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.