Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome

Abstract

Aims: We investigated the incidence, risk factors, clinical characteristics, and outcomes of pulmonary embolism (PE) in patients with COVID-19 attending emergency departments (EDs), before hospitalization.

Methods and results: We retrospectively reviewed all COVID-19 patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID-19 outbreak. COVID-19 patients without PE and non-COVID-19 patients with PE were included as control groups. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). We identified 368 PE in 74 814 patients with COVID-19 attending EDs (4.92‰). The standardized incidence of PE in the COVID-19 population resulted in 310 per 100 000 person-years, significantly higher than that observed in the non-COVID-19 population [35 per 100 000 person-years; odds ratio (OR) 8.95 for PE in the COVID-19 population, 95% confidence interval (CI) 8.51-9.41]. Several characteristics in COVID-19 patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, and chest pain (direct association) and chronic heart failure (inverse association). COVID-19 patients with PE differed from non-COVID-19 patients with PE in 16 characteristics, most directly related to COVID-19 infection; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID-19 patients affected smaller pulmonary arteries than in non-COVID-19 patients, although right ventricular dysfunction was similar in both groups. In-hospital mortality in cases (16.0%) was similar to COVID-19 patients without PE (16.6%; OR 0.96, 95% CI 0.65-1.42; and 11.4% in a subgroup of COVID-19 patients with PE ruled out by scanner, OR 1.48, 95% CI 0.97-2.27), but higher than in non-COVID-19 patients with PE (6.5%; OR 2.74, 95% CI 1.66-4.51). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations.

Conclusions: PE in COVID-19 patients at ED presentation is unusual (about 0.5%), but incidence is approximately ninefold higher than in the general (non-COVID-19) population. Moreover, risk factors and leg symptoms are less frequent, D-dimer increase is lower and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID-19 patients, mortality is higher in COVID-19 than in non-COVID-19 patients with PE.

Keywords: COVID-19; Clinical characteristics; Incidence; Outcome; Pulmonary embolism; Risk factors; SARS-CoV-2.

Graphical Abstract

Summary of the main findings of the study.

Figure 1

Study design and inclusion flow chart.

Figure 2

Baseline and acute episode characteristics found on multivariate analysis to be independently associated with COVID-19 patients with pulmonary embolism (cases) with respect to COVID-19 patients without pulmonary embolism (control groups A1 and A2, upper and middle panels) and non-COVID-19 patients with pulmonary embolism (control group B, lower panel). *Sensitivity analysis is presented only by blue figures (no graphs) and was run by using only patients with SARS-CoV-2 infection microbiologically confirmed in the case group (n = 271, 73.6%), control group A1 (n = 271, 73.6%), and control group A2 (n = 275, 74.7%). CI, confidence interval; OR, odds ratio.

Figure 3

Imaging findings in patients with pulmonary embolism, comparing those with (cases) and without (control group B) COVID-19. *Comparison between cases and control group B was performed by chi-square test for trend. DVT, deep vein thrombosis; PA, pulmonary artery; RV, right ventricle.

Figure 4

Number of COVID-19 patients diagnosed with pulmonary embolism along the study period, and anticoagulation regimen provided in the emergency department after the diagnosis of pulmonary embolism. LMWH, low-molecular-weight heparin; PE, pulmonary embolism.

Figure 5

Outcomes of patients with COVID-19 and pulmonary embolism compared with COVID-19 patients without pulmonary embolism (control groups A1 and A2) and non-COVID-19 patients with pulmonary embolism (control group B). *Sensitivity analysis is presented only by blue figures (no graphs) and was run using only patients with SARS-CoV-2 infection microbiologically confirmed in the case group (n = 271, 73.6%), control group A1 (n = 271, 73.6%) and control group A2 (n = 275, 74.7%). ¹Adjusted for recent immobilization and chronic heart failure. ²Adjusted for dyspnoea, cough, fever, chest pain and leg swelling/pain as clinical complaints, lactate dehydrogenase, leucocytes, platelets, D-dimer, and ground-glass lung opacities on chest X-ray (missing values were replaced using multiple imputation). ³Adjusted for immunosuppressed and chronic heart failure. ⁴Adjusted by dyspnoea, cough, fever, chest pain, leg swelling/pain as clinical complaints, creatinine, D-dimer, and interstitial lung infiltrates and cardiomegaly on chest X-ray (missing values were replaced using multiple imputation). ⁵Adjusted for age, active cancer, recent immobilization, chronic oestrogen therapy, asthma, active smoker, and chronic heart failure. ⁶Adjusted for dyspnoea, cough, fever, diarrhoea and leg swelling/pain as clinical complaints, haemoglobin, D-dimer, and lung interstitial bilateral infiltrates and ground-glass opacities on chest X-ray (missing values were replaced using multiple imputation). CI, confidence interval; ICU, intensive care unit; OR, odds ratio; PE, pulmonary embolism.