Inflammatory response in lungs and extrapulmonary sites detected by [18F] fluorodeoxyglucose PET/CT in convalescing COVID-19 patients tested negative for coronavirus

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an ongoing global pandemic of coronavirus disease 2019 (COVID-19). The challenges associated with imaging infected patients have resulted, to date, in a paucity of metabolic imaging studies of patients with severe COVID-19 infection. Furthermore, it remains unclear if any abnormal metabolic events are taking place in patients who have recovered from COVID-19.

Purpose: To use [¹⁸F] fluorodeoxyglucose ([¹⁸F] FDG) positron emission tomography/computed tomography (PET/CT) to measure metabolic activity in inflamed organs of patients convalescing post severe COVID-19 infection.

Materials and methods: A prospective study was performed in seven convalescing patients who were recovering from severe COVID-19 infection in February 2020. Prior to [¹⁸F] FDG PET/CT, all patients had received two consecutive negative results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 nucleic acid. Clinical intake including symptoms, treatment, laboratory test results, and follow-up was performed. The PET/CT images of COVID-19 patients were compared to a control group of patients that were matched for age and sex.

Results: Residual pulmonary lesions were present in all patients and maximum standard uptake value (SUVmax), average standard uptake value (SUVavg), maximum CT intensity (CTmax), and average CT intensity (CTavg) were all significantly greater than in the control group (p < 0.01 for all). In addition, SUVmax and SUVavg were significantly greater in the mediastinal lymph node and liver, and SUVmax was significantly greater in the spleen, of COVID-19 patients compared with controls (p < 0.05 for all). For the spleen, SUVmax (r² = 0.863, p = 0.003) and SUVavg (r² = 0.797, p = 0.007) were significantly correlated with blood lymphocyte count, and which was below the normal range in five of the seven (71.4%) patients convalescing post severe COVID-19 infection.

Conclusion: [¹⁸F] FDG PET/CT quantitative analysis has shown that significant inflammation remained in lungs, mediastinal lymph nodes, spleen, and liver after two consecutive negative RT-PCR tests in patients convalescing post severe COVID-19 infection.

Keywords: Coronavirus disease 2019; PET/CT; Severe acute respiratory syndrome coronavirus 2; [18F] Fluorodeoxyglucose.

Fig. 1

PET/CT images of a patient (A1–L1) and a control subject (A2–L2). The first and second, third and fourth, and fifth and sixth columns refer to CT, PET, and fused PET/CT images, respectively. The chest CT image shows consolidations in the bilateral lower lungs (A1, arrows; CTmax, 72, CTavg, 18) and the corresponding chest PET image shows increased [¹⁸F] fluorodeoxyglucose ([¹⁸F] FDG) uptake in the residual pulmonary lesions (B1, arrows; SUVmax, 6.1, SUVavg, 3.8). Lung PET/CT fusion image (C1). The mediastinum CT image shows a normal mediastinal lymph node (D1, arrow; CTmax, 56, CTavg, 24; short diameter, 7 mm). However, the corresponding mediastinum PET image shows increased [¹⁸F] FDG uptake in the mediastinal lymph node (E1, arrow; SUVmax, 5.9, SUVavg, 4.6); mediastinum PET/CT fusion image (F1). The abdominal CT image shows a normal spleen and liver (G1, arrows; spleen, CTmax, 102, CTavg, 46; liver, CTmax, 131, CTavg, 51). However, the corresponding abdominal PET image shows increased [¹⁸F] FDG uptake in spleen and liver (H1, arrows; spleen, SUVmax, 4.8, SUVavg, 3.0; liver, SUVmax, 4.6, SUVavg, 2.8). The abdomen PET/CT fusion image is also shown (I1), as are the coronal CT (J1), PET (K1), and fused PET/CT (L1) images. In the control subject, the chest CT image shows normal bilateral lungs (A2, arrows; CTmax, − 299, CTavg, − 569) and the chest PET image shows no increased [¹⁸F] FDG uptake in the bilateral lungs (B2, arrows; SUVmax, 0.7, SUVavg, 0.6). Lung PET/CT fusion image (C2). The mediastinum CT image shows a normal mediastinal lymph node (D2, arrow; CTmax, 59, CTavg, 24; short diameter, 8 mm) and the mediastinum PET image shows no increased [¹⁸F] FDG uptake in the mediastinal lymph node (E2, arrow; SUVmax, 2.2, SUVavg, 2.1). Mediastinum PET/CT fusion image (F2). The abdominal CT image shows a normal spleen and liver (G2, arrows; spleen, CTmax, 93, CTavg, 47; liver, CTmax, 104, CTavg, 56) and the abdominal PET image shows no increased [¹⁸F] FDG uptake in the spleen or liver (H2, arrows; spleen, SUVmax, 2.2, SUVavg, 1.7; liver, SUVmax, 3.0, SUVavg, 2.3). Abdomen PET/CT fusion image (I2) is also shown, as are the coronal CT (J2), PET (K2), and fused PET/CT (L2) images

Fig. 2

Graphs of the average values of SUVmax and SUVavg (A) and CTmax and CTavg (B) in ROIs in the residual pulmonary lesion, adjacent normal-appearing lung tissue, mediastinal lymph node, spleen, liver, left ventricular lateral wall, small intestine wall, and left and right renal cortex of the convalescing COVID-19 patients compared with the controls. Error bars represent the standard deviation. Parameters marked with asterisks are significant (p < 0.05)

Fig. 3

Correlations between SUVmax, SUVavg, CTmax, and CTavg of spleen and lymphocyte count (A, B) or C-reactive protein (C, D) of peripheral blood in the convalescing COVID-19 patients were assessed using Spearman’s rank correlation analyses. The lymphocyte count was strongly correlated with the SUVmax (r² = 0.863, p = 0.003) and SUVavg (r² = 0.797, p = 0.007) (A). However, the lymphocyte count was not significantly correlated with CTmax (r² = 0.368, p = 0.148) or CTavg (r² = 0.127, p = 0.432) (B). The C-reactive protein was not significantly correlated with SUVmax (r² = 0.011, p = 0.819), SUVavg (r² = 0.001, p = 0.939 (C), CTmax (r² = 0.184, p = 0.337), or CTavg (r² = 0.081, p = 0.535) (D)