Vasculitis changes in COVID-19 survivors with persistent symptoms: an [18F]FDG-PET/CT study

Abstract

Purpose: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) was able to demonstrate a persistent inflammatory process.

Methods: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [¹⁸F]FDG positron emission tomography/computed tomography ([¹⁸F]FDG-PET/CT). Whole-body [¹⁸F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [¹⁸F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses.

Results: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46-80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [¹⁸F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [¹⁸F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls.

Conclusion: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.

Keywords: Infection; Inflammation; Long COVID; SARS-CoV-2; Vasculitis; [18F]FDG-PET/CT.

Fig. 1

[¹⁸F]FDG uptake in blood vessels (title). Box-and-whisker plot of the total vascular uptake (a) and of the target-to-blood pool ratio (b) (significance is reported only for p values ≤ 0.05)

Fig. 2

Scatterplot of the correlation between target-to-blood pool ratio and laboratory tests in a subset of recovered SARS-CoV-2 patients: a C-reactive protein (CRP) peak, d lactate dehydrogenase (LDH) peak, c D-dimer peak

Fig. 3

Box-and-whisker of the size of the proximal ascending aorta (significance is reported only for p values ≤ 0.05)

Fig. 4

[¹⁸F]FDG-PET/CT in recovered SARS-CoV-2 patients (title). Example of [¹⁸F]FDG bone marrow uptake in a 50-year-old female patient with persisting symptoms (dyspnea and fatigue) lasting for almost 3 months (MIP in a). She took only symptomatic treatment during the acute phase of infection. Example of [¹⁸F]FDG vascular uptake in a 51-year-old male patient with persisting symptoms (fatigue) lasting for almost 4 months. He developed an acute respiratory distress syndrome, which finally required endotracheal intubation and invasive ventilation. Visually, the [¹⁸F]FDG uptake was scored as grade 2 at the ascending aorta, the aortic arch (b) and the descending aorta (c)