Mapping COVID-19 functional sequelae: the perspective of nuclear medicine

Abstract

Severe acute respiratory syndrome coronavirus 2 infection is capable of affecting several organs. Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage. The impairment of four organs stands out among severe patients: lung, heart, kidney, and endothelium. The nuclear medicine field holds accurate and safe exam techniques, such as positron emission tomography-computed tomography and scintigraphy, that allow the anatomophysiological study of the majority of human organ systems. By choosing the most appropriate method and radiopharmaceutical, analyzing the presence of inflammation, fibrosis, changes in perfusion, and function of desired organs is possible. Therefore, its use in the monitoring of patients with coronavirus disease 2019 becomes relevant, especially for monitoring sequelae. In this review, we discuss the use of Nuclear Medicine in the detection, monitoring, and therapeutic evaluation of pulmonary and extrapulmonary sequelae by coronavirus disease 2019.

Keywords: COVID-19; Nuclear medicine; PET/CT; scintigraphy; sequelae.

Figure 1

Actions of angiotensin 1-7 (ANG 1-7), by-product of angiotensin 1 (ANG 1) and consequences of its blockage. Angiotensin-converting enzymes (ACE) 1 and 2 act on ANG 1 and on angiotensin 2 (ANG 2). Spike (S) protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human cell’s ACE2 receptor, which consequently reduces ACE2 activity. TMPRSS2 is the enzyme responsible for the cleavage of the S protein from SARS-CoV-2, allowing its binding with ACE2. Created with Biorender.com.

Figure 2

Possible Mechanisms of Acute Cardiac Injury in COVID-19. A. Patients with preexisting conditions are more reactive to inflammatory states and might have higher risk of cardiac injury during infections, such as SARS-CoV-2. B. It is suggested that SARS-CoV-2 itself can infect myocardial and endothelial cells, via ACE2 receptors present on their cell membrane surface. Although plausible, no evidence of direct myocardial infection has been found. C. The injury can also occur due to indirect mechanisms resulting from hypoxia, prothrombotic state, and systemic inflammatory response syndrome. ACE2: angiotensin-converting enzyme 2; DM: diabetes mellitus; SAH: systemic arterial hypertension; CVDs: cardiovascular diseases; COVID-19: Coronavirus Disease 2019; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2. Created with Biorender.com.

Figure 3

Mapping of COVID-19’s functional sequelae with Nuclear Medicine. Created with Biorender.com.

Figure 4

¹⁸F-FDG PET/CT use in diagnosis and monitoring of lung inflammation caused by SARS-CoV-2. Male, 48 y/o, had follicular lymphoma. He was given chemotherapy until April, 2020 and is currently receiving rituximab. In June, he had mild flu-like symptoms and tested positive for COVID-19. After 17 days, due to a persistent daily fever, a ¹⁸F-FDG PET/CT was performed and demonstrated glycolytic hypermetabolism in areas of multiple opacities with “ground-glass” attention and sparse pulmonary consolidations with air-permeable bronchograms in both lungs (A). These findings were related to COVID-19 and not to lymphoma. One month later, the patient presented clinically well, although with persistent fever episodes. He underwent another ¹⁸F-FDG PET/CT that has shown impressive improvement of pulmonary inflammatory lesions and no lymphoma evidence (B) (images from the authors’ personal files).