Dear Editor,
Pulmonary embolism (PE) in the setting of COVID-19 is related to the procoagulant
state as evidenced by the increased D-dimer levels and in situ thrombosis [1,2] and
it usually involves the segmental/subsegmental arteries. [2] Some data have shown
that mortality is higher among patients with COVID-19 and PE compared with non-COVID-19
PE. [3] The COVID-19 pandemic has led to marked reductions in cardiovascular testing
in the United States (US). [4] However, the impact of the COVID-19 pandemic on the
diagnosis and management of PE is not well studied. To better describe the characteristics
and the impact of COVID-19 infection on the management strategies and outcomes of
patients with acute PE, we performed a comprehensive analysis of a nationally representative
database in the US.
We used the Nationwide Readmissions Database (NRD) for the years 2019 and 2020 to
extract the study cohort. All patients aged 18 years or older with any discharge diagnosis
of PE in the years 2019 and 2020 were included. Pregnancy-related PE (n=2,871) and
admissions with missing data on mortality (n=169) were excluded. We examined the differences
in all-cause in-hospital mortality, length of stay (LOS), cost, intracranial hemorrhage
(ICH), non-ICH bleeding, and 30-day urgent readmission rates between admissions with
and without COVID-19 in the year 2020. We also examined the differences in outcomes
among admissions with non-COVID-19 PE in the year 2019 versus 2020. All analyses were
performed according to the Healthcare Cost and Utilization Project (HCUP) regulations
for statistical analysis. Multivariable logistic regression analyses were used to
adjust for the differences in baseline and hospital characteristics, PE severity and
different management strategies. Additionally, we performed a subgroup analysis for
patients with high-risk PE (i.e., cardiogenic shock). Statistical analyses were performed
using IBM SPSS Statistics for Windows (version 28.0. Armonk, NY: IBM Corp).
A total of 786,963 weighted hospitalizations with acute PE were included in the analysis,
374,122 (47.5%) were admitted in 2019 and 412,842 (52.5%) in 2020. Among those admitted
in 2020, 46,825 (11.3%) weighted hospitalizations had concomitant COVID-19 infection.
The use of surgical embolectomy, catheter-directed interventions (CDI) and mechanical
circulatory support (MCS) devices was less common among admissions with COVID-19 infection.
The use of vasopressors and mechanical ventilation was higher among admissions with
underlying COVID-19 infection. (Table 1
)
Table 1
Characteristics and outcomes of patients with acute PE admitted in the year 2020.
Table 1
PE without COVID-19 (n=366,017)
PE with COVID-19 (n=46,825)
P value
Age, median (IQR)
66 (54-76)
66 (55-76)
0.04
Female
183,709 (50.2%)
19,462 (41.6%)
<0.001
Smoking
85,873 (23.5%)
10,022 (21.4%)
<0.001
Comorbidities
Morbid obesity
46,862 (12.8%)
6,343 (13.5%)
0.007
Hypertension
233,817 (63.9%)
29,628 (63.3%)
0.118
Diabetes mellitus
96,420 (26.3%)
16,634 (35.5%)
<0.001
Anemia
98,656 (27.0%)
10,384 (22.2%)
<0.001
Coagulopathy
49,278 (13.5%)
8,127 (17.4%)
<0.001
Pulmonary hypertension
41,094 (11.2%)
2,460 (5.3%)
<0.001
Chronic pulmonary disease
96,833 (26.5%)
10,084 (21.5%)
<0.001
Atrial fibrillation/flutter
62,518 (17.1%)
6,857 (14.6%)
<0.001
Heart failure
87,636 (23.9%)
7,595 (16.2%)
<0.001
Chronic kidney disease
61,036 (16.7%)
7,431 (15.9%)
0.008
Chronic liver disease
4,443 (1.2%)
248 (0.5%)
<0.001
Connective tissue diseases
13,867 (3.8%)
1,482 (3.2%)
<0.001
CAD
69,080 (18.9%)
7,197 (15.4%)
<0.001
PAD
14,340 (3.9%)
1,163 (2.5%)
<0.001
Carotid disease
3,012 (0.8%)
253 (0.5%)
<0.001
Prior stroke
30,798 (8.4%)
3,217 (6.9%)
<0.001
Malignancy
80,199 (21.9%)
3,026 (6.5%)
<0.001
Metastatic
43,930 (12.0%)
1,005 (2.1%)
<0.001
Presentation and severity
Saddle PE
26,195 (7.2%)
1,950 (4.2%)
<0.001
Acute cor pulmonale
27,267 (7.4%)
1,803 (3.9%)
<0.001
High-risk PE (Cardiogenic shock)
8,647 (2.4%)
846 (1.8%)
<0.001
Concomitant DVT
122,654 (33.5%)
8,811 (18.8%)
<0.001
Hospital characteristics
Large hospital
202,418 (55.3%)
24,998 (53.4%)
0.018
Teaching hospital
273,508 (74.7%)
34,137 (72.9%)
0.003
Medicare
203,423 (55.6%)
24,366 (52.0%)
<0.001
Transferred from other hospital
13,297 (3.6%)
2,203 (4.7%)
<0.001
Treatment modalities
Systemic thrombolysis
8,687 (2.4%)
1,088 (2.3%)
0.70
Surgical embolectomy
596 (0.2%)
17 (0.04%)
<0.001
CDT
9,549 (2.6%)
468 (1%)
<0.001
CDE
410 (1.8%)
41 (0.8%)
<0.001
IVC filter
22,557 (6.2%)
1,122 (2.4%)
<0.001
Circulatory and ventilatory support
Vasopressors
5,628 (1.5%)
1,443 (3.1%)
<0.001
Mechanical ventilation
31,681 (8.7%)
9,739 (20.8%)
<0.001
Mechanical circulatory support
1,459 (0.4%)
84 (0.2%)
<0.001
Impella
392 (0.1%)
22 (0.0%)
0.03
ECMO
702 (0.2%)
55 (0.1%)
0.03
IABP
537 (0.1%)
10 (0.0%)
<0.001
Outcomes
In-hospital mortality
27,240 (7.4%)
9,285 (19.8%)
<0.001
Intracranial hemorrhage (ICH)
5,847 (1.6%)
604 (1.3%)
<0.001
Non-ICH
39,744 (10.9%)
5,261 (11.2%)
<0.001
Length of stay, days (IQR)
4 (2-8)
7 (4-14)
<0.001
Cost of stay, US Dollars (IQR)
12,462 (7,056-25,364)
17,212 (9,079-37,833)
<0.001
30-day unplanned readmissions*
46,890/308,437 (15.2%)
2,596/25,967 (10.0%)
<0.001
⁎
After excluding those who died during the index admissions and those who were admitted
in December of each calendar year.
CDI: catheter-directed intervention, PE: pulmonary embolism, IQR: interquartile range,
MI: myocardial infarction, PCI: percutaneous coronary intervention, CABG: Coronary
artery bypass grafting, DVT: deep venous thrombosis, CDT: catheter-directed thrombolysis,
CDE: catheter-directed embolectomy, US: ultrasound, IVC: inferior vena cava, ECMO:
extracorporeal membrane oxygenation, IABP: intra-aortic balloon pump, IQR: interquartile
range.
The rate of all-cause in-hospital mortality was higher among admissions with COVID-19
infection (7.4% vs. 19.8%, P<0.001). The rate of ICH was slightly lower (1.6% vs.
1.3%, P<0.001) and non-ICH was slightly higher (10.9%. vs. 11.2%, P<0.001) in admissions
with COVID-19 infection. Admissions with COVID-19 infection had longer LOS and higher
cost. (Table 1) On multivariable analysis, COVID-19 infection was independently associated
with higher mortality (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI]
2.56, 2.87, P<0.001), higher risk of non-ICH (aOR 1.10, 95% CI 1.05, 1.15, P<.001),
and lower risk ICH (aOR 0.59, 95% CI 0.51, 0.68, P<0.001). Among admissions with high-risk
PE, in-hospital mortality was higher among those with COVID-19 (36.9% vs. 69.7%, aOR
2.64, 95% CI 2.10, 3.33, P<0.001).
In the analysis restricted to non-COVID-19 PE admissions, the prevalence of saddle
PE (6.2% vs. 7.2%, P<0.001), cor pulmonale (6.8% vs. 7.4%, P=0.008), and cardiogenic
shock (2.1% vs. 2.4%, P=0.007) was higher in 2020. There was no difference in the
rate of utilization of systemic thrombolysis (2.4% vs. 2.4%, P=0.76), surgical embolectomy
(0.2% vs. 0.2%, P=0.85), catheter-directed thrombolysis (2.5% vs. 2.6%, P=0.52), vasopressors
(1.3% vs. 1.5%, P=0.20), and MCS devices (0.4% vs. 0.4%, P=0.92) between 2019 and
2020. All-cause in-hospital mortality (7.0% vs. 7.4%, P<0.001) was slightly higher
in 2020. However, after adjustment, there was no difference in mortality between both
years (2020 vs. 2019: aOR 1.04, 95% CI 0.99, 1.09, P=0.14).
In this nationwide analysis, we examined the association between COVID-19 infection
and the management and outcomes of acute PE during the early wave of the pandemic.
The main findings are as follows: 1) Patients with COVID-19 and PE were less likely
to receive CDI, surgical embolectomy, and MCS devices, compared with those without
COVID-19 infection. 2) COVID-19 infection was independently associated with a higher
incidence of all-cause in-hospital mortality, higher costs, and longer LOS compared
to patients without COVID-19. 3) In analyses restricted to non-COVID-19 PE, patients
admitted in 2020 versus 2019 were sicker but there was no difference in the utilization
of advanced therapies and in in-hospital mortality.
Similar to prior studies, [3] we found that patients with COVID-19 and PE had fewer
comorbidities and risk factors for PE, indicating that COVID-19 itself is the predisposing
factor for PE. Also, fewer patients with COVID-19 PE had DVT or saddle PE, suggesting
that in situ thrombosis plays a role in the pathogenies of COVID-19 PE. [5] In the
current analysis, COVID-19 infection was associated with a 2.7-fold increase in in-hospital
mortality among patients with PE. This can be related to severe COVID-19 infection
itself leading to systemic inflammation, shock, multiorgan failure and respiratory
failure with involvement of the lung parenchyma. [3,6] Additionally, PE with COVID-19
infection is associated with an increased risk of mechanical ventilation and ICU admission.
[7]
In our analysis, patients with PE and COVID-19 infection during the early wave of
the pandemic were less likely to receive surgical embolectomy, CDI, or MCS. This may
be attributed to patients' isolation, instability, and difficulties in transferring
patients safely to the catheterization laboratory or operating room without exposing
the healthcare team. Additionally, patients may have not been offered invasive procedures
due to the risk of transmission or poor prognosis.
We found that the care of patients with acute PE was generally not affected during
the early wave of the COVID-19 pandemic. We noticed that in 2020, compared with 2019,
patients with non-COVID PE were sicker suggesting that only patients with more severe
symptoms presented to the emergency departments (ED) or that patients with less severe
presentations were discharged directly from the ED. Despite that, there was no decline
in the utilization of advanced therapies and no difference in in-hospital mortality
between 2019 and 2020 for patients without COVID-19, which suggests that care for
essential services such as PE was maintained in 2020 despite significant system constraints.
There are some limitations to this study. Being a retrospective observational study,
it is prone to selection bias. Given the administrative nature of the NRD, the study
is subject to coding errors and data quality at the site of collection, without the
ability to adjudicate accuracy. Clinical, laboratory, and imaging data as well as
data on prescribed medications including the type and dose of thrombolytics are lacking
from the NRD, which may have impacted the clinical outcomes. Long-term outcomes could
not be assessed, and we could not also ascertain PE-specific mortality from NRD. [8]
Finally, our findings are restricted to the early wave of the pandemic when the therapies
for COVID-19 were limited, and widespread vaccines were unavailable.
In this nationwide observational cohort of patients admitted with PE during the early
wave of the pandemic, COVID-19 infection was independently associated with a higher
risk of all-cause in-hospital mortality among PE admissions. There was no decline
in utilization of advanced therapies and no difference in-hospital mortality among
patients with acute PE without COVID-19 infection in the year 2019 vs. 2020.
Sources of funding
None
Declaration of Competing Interests
None