SARS-CoV-2: what it is, how it acts, and how it manifests in imaging studies

Abstract

COVID-19 is a disease with many clinical, biochemical, and radiological signs that has a predilection for the lungs, probably because of the high number of ACE-2 receptors in this organ. The infection of cells activates proinflammatory substances, causing diffuse alveolar damage, which is the histopathological basis of ARDS. The exudative phase would manifest as ground-glass opacities and consolidation, and the proliferative phase would manifest as a tendency toward a more linear morphology. Both CT and PET/CT findings support the inflammatory character of the lung lesions in the initial phase of the disease and in patients with mild-moderate disease. Severe cases have pulmonary hypoperfusion that is likely due to abnormal alveolar ventilation and perfusion. On the other hand, a prothrombotic state increases the risk of thromboembolic disease through the activation of coagulation and platelet pathways with the production of fibrin degradation products (D-dimer) and consumption of platelets.

Keywords: COVID-19; PET/TC; Percusión pulmonar PBV; SARS-2; SARS-CoV-2; TC alta resolución; TC doble energía; dual-energy CT; high-resolution CT; lung perfusion blood volume.

Figure 1

A) Structure of SARS-CoV-2 (SARS-2). Enveloped single-stranded RNA virus with surface glycoproteins. The virus's S or spike protein gives it its characteristic crown-like shape and binds to ACE2 receptors on cells. B) SARS-2 virus infection and replication. The virus binds to the ACE2 receptors of the host cell (in this case, the type II lung cell) to enter the cell by endocytosis through the cell membrane. The viral envelope is destroyed through proteolysis; this releases the RNA, which replicates and then, through the membranes of the cell's Golgi bodies and endoplasmic reticulum, forms complete virions (viral inclusions in tissues on autopsy). These virions are eliminated by means of exocytosis through the cell membrane. Other virus proteins enable the virus to enter the nucleus and alter it structurally and functionally, leading to apoptosis, or programmed cell death. C) The cell involvement caused by the virus prompts activation of macrophages, endothelial cells, dendritic cells, etc. These produce cytokines (IL-1, IL-6 and IL-8) and cause T lymphocytes to activate as a rapid immune response. However, a response that is not rapid (delayed response) or simply not well regulated causes overproduction through IFN and TNF, resulting in greater activation of macrophages and other cells (cytokine storm). COX-2: cyclooxygenase-2; IFN: interferon; IL: interleukin; TNF: tumour necrosis factor.

Figure 2

A) A 61-year-old man (healthcare worker). He had fever, asthenia, muscle pain and cough for 4 days (positive PCR). In addition, a chest X-ray with blurring of the right cardiac silhouette (the patient had pectus excavatum) showed a subtle increase in density in the left upper lobe (LUL); as a result, a CT scan was ordered. The CT scan revealed a lesion with a crazy-paving pattern and air bronchogram in the LUL; no other lesions were seen anywhere else in the lung. B) A 66-year-old man had signs and symptoms suggestive of COVID-19 for 6 days. He had significant fever and cough with no notable expectoration. Ageusia and anosmia. No dyspnoea. Negative PCR. A CT scan showed increases in peripheral bilateral density with a posterior predominance, exhibiting a ground-glass pattern.

Figure 3

Other radiological patterns on CT in patients with COVID-19: A) Crazy-paving pattern. B) Vascular thickening inside lesions. C) Halo sign. D) Vacuolisation. E) Reversed halo sign. F) Spontaneous pneumothorax.

Figure 4

CT on axial (A) and coronal (B) planes. A 56-year-old man, diabetic, with signs and symptoms of malaise and 39 °C fever, without cough, for 10 days. He was treated with hydroxychloroquine, ceftriaxone and azithromycin. On his sixth day of admission, as he was not following a favourable clinical course, a decision was made to treat him with corticosteroids (22/04/2020); after four days of this treatment, he showed clinical and radiological improvement (28/04/2020).

Figure 5

Proposed radiopathological correlation of the different stages of acute respiratory distress syndrome in COVID-19. A) Exudative or early phase, featuring alveolar oedema with haemorrhage and hyaline membranes. Pro-inflammatory substances (IL-6) with activation of cells (macrophages) causing endothelial damage with vascular ingurgitation. B) Later phase with progression of abnormalities (areas of consolidation). C) Proliferative phase, with large numbers of alveolar hyaline membranes and hypertrophy of type II lung cells. Increase in collagen leading to formation of interstitial fibrosis. Formation of fibrin thrombi (microvascular thrombosis). See text.

Figure 6

A patient with COVID-19 and pulmonary thromboembolism. D-dimer 12,556 ng/mL. CT with intravenous contrast. A) This shows filling defects in distal (segmental) pulmonary arteries. B) Strikingly, the axial image shows zones of lower density in the areas of lung consolidation, suggesting zones of infarction. This sign, when detected, should alert the clinician to the possibility of pulmonary thromboembolism and prompt reassessment of distal and small vessels for its presence.

Figure 7

A woman (healthcare worker) with suspected infection. Positive PCR. Normal chest X-ray. Treatment was started with hydroxychloroquine and azithromycin. Over the next 4 days she showed persistent fever and gradual worsening with dyspnoea and desaturation. Increase in inflammatory markers (IL-6). Elevation of D-dimer from 322 to more than 4000 ng/mL. A) CT, lung window showing extensive bilateral peripheral lesions. B) CT angiography (dual-energy) showing no evidence of pulmonary thromboembolism. Maximum intensity projection (MIP) reconstruction enabling visualisation of distal vessels, including inside areas of lung consolidation. C) PBV imaging (Lung Analysis software program; Siemens Healthineers) showing patchy areas of perfusion defects essentially corresponding to areas of consolidation that exhibit lower contrast uptake (uptake of 1.3 HU) compared to areas of healthy lung (uptake of 63.4 HU). D) Coronal reconstruction with narrower density thresholds, showing lower uptake by peripheral lung areas (hypoperfusion), more pronounced on the right side (see text).

Figure 8

Patient with COVID-19 who had several pulmonary lesions with high attenuation. Dual-energy CT. CT angiography (dual-energy) showing no evidence of pulmonary thromboembolism (PTE). A) PBV imaging exhibiting no perfusion defects characteristic of PTE and showing homogeneous perfusion of the lung parenchyma. B) Lung window showing one of the lung lesions with the reversed halo sign.

Figure 9

A patient with COVID-19. Dual-energy CT. A and B) Single-energy imaging showing right posterior and basal consolidation uptake, more obvious on low-energy single-energy imaging (40 KeV). C) Image from iodine map showing lesion uptake with an increase in density of 47 HU.

Figure 10

A 71-year-old man with a history of colon carcinoma, in whom monitoring revealed an indeterminate pulmonary nodule. A) Image from CT with lung window. B) Image from a PET/CT scan showing increased areas of bilateral density characteristic of COVID-19, which exhibit metabolic uptake.