Keywords
pulmonary embolism - perfusion imaging - SPECT/CT - COVID-19 - inflammation - pneumonia
Introduction
Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused
by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the
symptomatic patient, it is predominantly an acute respiratory disease accompanied
by fever, shortness of breath, and cough, among other symptoms. The ongoing global
pandemic has to date infected over 16.5 million people, resulting in approximately
655,000 deaths worldwide.[1]
Consequential lung inflammation, resulting in COVID-19 associated pneumonia, is usually
diagnosed by characteristic changes on chest X-ray or thoracic computed tomography
(CT) imaging. Typically, chest CT demonstrates nonspecific bilateral abnormalities,
with ground glass opacities in milder forms progressing to widespread consolidation
in more severe forms of disease.[2]
[3]
[4]
[5] Eventually, progressive atypical respiratory system distress may develop over time,
and other organ systems are frequently affected including the central nervous system,
heart, and kidneys. This may be related to the propensity of SARS-CoV-2 and related
viruses for the angiotensin-converting enzyme 2 receptor, which is a relatively common
functional receptor in multiple organ systems.[6]
[7] Furthermore, an important complication of COVID-19 infection is thromboembolic disease
and effective, even high-dose prophylaxis is required and recommended according to
clinicians treating COVID-19 patients. There is an increasing body of evidence that
blood clots are a major cause of multisystem organ dysfunction, including the respiratory
failure in severe cases of SARS-CoV-2 infection.[8]
[9]
[10]
Case Report
A 49-year-old female with multiple comorbidities including alcoholic liver cirrhosis
with sequelae of portal hypertension and poorly controlled hypothyroidism presented
to the hospital with worsening diffuse abdominal pain and distension over a 2-month
period. Upon arrival to the emergency room, the patient was saturating 95% on 2 L
of oxygen via nasal cannula and was afebrile. The patient's laboratory values were
notable for acute kidney injury with creatinine of 1.5 (baseline Cr 0.9). CT of the
chest, abdomen, and pelvis was performed that demonstrated cirrhotic liver and massive
volume of intra-abdominal ascites. Chest CT was unremarkable, but the patient was
placed under investigation for COVID-19 disease given the current high prevalence
in the New York region. Nasopharyngeal swab was obtained and polymerase chain reaction
(PCR) for SARS-CoV-2 initially came back negative.
On day 4 of hospitalization, the patient developed some shortness of breath, and was
noted to be saturating at 91% on 2 L of oxygen via nasal cannula, which improved to
99% on nasal cannula with oxygen flow rate of 4 to 5 L. The patient otherwise remained
afebrile. D-dimer was obtained and was elevated at 1,303 ng/mL. Given the patient's
poor kidney function and negative chest CT 3 days earlier, nuclear ventilation–perfusion
lung scan was requested.
Per our institutional policy and national guidelines related to the coronavirus pandemic,
the ventilation portion of the lung scan was not obtained. Instead, just lung perfusion
imaging was performed using planar and single photon emission tomography/computed
tomography (SPECT/CT) acquisitions.
The chest CT portion of the study demonstrated new multiple bilateral, peripheral
predominant, consolidative lung opacities with reticulations typical of interstitial
COVID-19 pneumonia and small pleural effusions ([Fig. 1]). The SPECT images revealed markedly abnormal lung perfusion with heterogeneous
radiotracer distribution, including multiple large nonsegmental areas of reduced or
absent perfusion with “stripe sign” in both lungs characteristic of lung inflammation,
even without underlying parenchymal changes on corresponding CT images.[11] In addition, multiple subsegmental perfusion defects typical for small pulmonary
emboli were also observed ([Figs. 2] and [3]). Total preserved lung perfusion function was estimated to be approximately one-third
of normal function.
Fig. 1 Noncontrast chest computed tomography (CT) obtained as part of the lung perfusion
single-photon emission computed tomography/computed tomography scan (left) in the sagittal plane (left) demonstrating multiple peripheral consolidative opacities (arrows) with air bronchograms and reticulations in the left upper lobe. These findings are
characteristic of coronavirus disease 2019 pneumonia in the appropriate clinical setting.
Notably, contrast-enhanced chest CT (right) in the sagittal plane obtained 3 days prior was unremarkable, only demonstrating
subsegmental plate-like atelectasis in the left lower lobe.
Fig. 2 Chest computed tomography (CT) (upper left) and single-photon emission computed tomography-computed tomography (SPECT/CT) perfusion
images (upper right) in the axial plane at the mid lung level demonstrate multiple peripheral consolidative
lung opacities with reticulation predominantly in the left upper lobe as well as the
right upper lobe (arrowheads) with corresponding areas of decreased perfusion. A new small right-sided pleural
effusion has been also developed. SPECT perfusion imaging in the axial plane (left lower) reveals multiple small peripheral perfusion defects (thin arrows) corresponding to peripheral vascular territories on CT reflecting probable small
emboli. SPECT perfusion in the coronal plane (right lower) of the posterior lungs
demonstrates large areas of central perfusion defects (wide arrows) not corresponding to vascular territories (“stripe sign”).
Fig. 3 Single-photon emission computed tomography (SPECT) (left) and SPECT/CT perfusion images (right) in the axial plane near the lung bases demonstrate large areas of central perfusion
defects (wide arrows) not reflecting vascular territories. These may represent areas of inflammation with
characteristic 'stripe sign” (thin arrows) and without underlying CT abnormalities.
Given these findings, the patient was retested for COVID-19 and repeat PCR analysis
for SARS-CoV-2 was positive.
Discussion
Imaging is an essential aspect of management of COVID-19 patients to evaluate the
extent of different organ system involvement, severity, and progression of disease.
According to recent published radiology literature, the characteristic CT findings
of COVID-19 associated pneumonia most commonly include bilateral, peripheral ground-glass
opacities predominantly in the lower lobes accompanied by consolidation and cavitation
in more severe cases.[2]
[3]
[4] These imaging findings are nonspecific and are associated with other infectious
and noninfectious inflammatory diseases.[5] In the current critical review, Raptis et al argue that chest CT should not be used
as screening or diagnostic tool, but instead should be reserved for evaluation of
complications of COVID-19 pneumonia or for assessment if alternative diagnoses are
suspected.[12] The same conclusion was summed up in recent recommendations and position statements
of several national and international organizations. Furthermore, since chest CT findings
may be normal in up to 15% of individuals with COVID-19 infection, a normal chest
CT cannot exclude the disease with certainty. However, an initial chest CT is a useful
method in the rapid preliminary diagnosis of SAR-CoV-2 infection so that the suspected
patient may be isolated and treated in time.[13]
[14]
Evidence has also accumulated that a subgroup of patients with severe COVID-19 disease
develop cytokine storm syndrome.[15]
[16] In these cases, hyperinflammation due to rapid accumulation of T-cells and macrophages
results in release of massive level of cytokines into the bloodstream aiming to destroy
the offending pathogen causing numerous manifestations starting from the atypical
respiratory system distress and fever, and progressing to multiorgan system dysfunction
involving the heart, kidneys, and the central nervous system.[17]
[18] Thromboembolic disease giving rise to pulmonary embolism is an additional important
complication of SARS-CoV-2 infection. There is apparently a causal relationship as
severe inflammation and infection is a known precipitating factor for thromboembolism.
Researchers in Ireland confirmed that the diffuse bilateral inflammation observed
in COVID-19 is associated with significant pulmonary-specific vasculopathy that correlates
with disease severity. The unexpectedly high prevalence of thromboembolism among affected
patients and COVID-19 associated coagulopathy with elevated markers such as D-dimer
and fibrinogen has been increasingly recognized in regions with high disease prevalence.[19]
[20] A recent study from France revealed that 30% of patients with COVID-19 infection
had acute pulmonary emboli on pulmonary computed tomography angiography, a striking
percentage.[21] Similarly, investigators from the Netherlands reported remarkably high, 31% incidence
of thrombotic complications in intensive care unit patients with COVID-19 despite
at least standard low-dose heparin prophylaxis.[8] The first series of autopsies in the United States from New Orleans showed bilateral
diffuse alveolar damage with lymphocytic infiltrate predominantly in the interstitial
spaces and fibrin thrombi within the capillaries and small vessels throughout the
lungs.[22] Reported autopsy results from Italy indicate that in addition to diffuse inflammatory
infiltrate, major relevant lung finding is the presence of platelet-fibrin thrombi
in small arterial vessels that is important in the clinical context of coagulopathy
dominating the clinical course in these patients.[23]
While elevated D-dimer is a frequent finding in COVID-19 infection, it is not specific
for the diagnosis of venous thromboembolism.[15] On the other hand, CT angiography may contribute to, or even cause development of
acute kidney injury in these patients already at risk of renal failure. Therefore,
consideration should be given to lung perfusion radionuclide scan as the preferred
imaging modality when pulmonary embolism is suspected in SARS-CoV-2 patients. Furthermore,
based on the presented case we postulate that functional abnormalities evident as
widespread perfusion reduction on radionuclide perfusion tomographic images may precede
abnormal morphological findings on chest CT in some patients. The extent of abnormal
perfusion defects likely reflects widespread lung inflammation and multiple small
thromboemboli without corresponding structural damage on CT images was an unexpected
finding in the presented case of patient with COVID-19 pneumonia. These findings are
in accordance with the reported clinical course of disease and underlying pathological
findings. This patient had multiple comorbidities and there are other possible explanations
for the perfusion defects including vascular and oxygenation changes from a pulmonary
manifestation of cirrhosis or portal hypertension, as well as long-term lung damage
and possible autoimmune disease linked to the poorly controlled hypothyroidism. Chest
CT remains an important initial imaging approach in COVID-19 patients with the addition
of CT angiography when thromboembolism is suspected. Functional perfusion imaging
in combination with low-dose CT (SPECT/CT) is an alternative study in COVID-19 patients
when thromboembolism is suspected. In addition, SPECT/CT perfusion imaging may visualize
and assess early lung parenchymal changes caused by interstitial pneumonia and related
comorbidities such as pulmonary embolism, pulmonary hypertension, and heart failure.[11] In institutions without a SPECT/CT camera, SPECT imaging alone may be useful especially
if it can be fused with chest CT for correlation.
Conclusion
Comorbidity of pneumonia and pulmonary embolism is a frequent finding in COVID-19
infection. Although chest CT is the mainstay for the evaluation of these lung pathologies,
hybrid SPECT/CT imaging technology can be useful as an adjunct or alternative study.
Lung perfusion SPECT/CT may identify pulmonary embolism including small subsegmental
emboli, as well as parenchymal lung changes on underlying chest CT images in patients
with COVID-19 disease. In this case study, we showed extensive SPECT/CT nonsegmental
defects that we hypothesize may indicate an early lung involvement or inflammatory
changes in SARS-CoV-2 infection.
This imaging approach should be considered in the management of COVID-19 patients,
and further evaluated in well-planned prospective clinical studies.
