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Id Subject Object Predicate Lexical cue
T1 0-76 Sentence denotes 18F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases
T2 78-86 Sentence denotes Abstract
T3 87-94 Sentence denotes Purpose
T4 95-264 Sentence denotes The aim of this case series is to illustrate the 18F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China.
T5 266-273 Sentence denotes Methods
T6 274-531 Sentence denotes We describe the 18F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January 13 and January 20, 2020, when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown.
T7 532-690 Sentence denotes A retrospective review of the patients’ medical history, clinical and laboratory data, as well as imaging findings strongly suggested a diagnosis of COVID-19.
T8 692-699 Sentence denotes Results
T9 700-811 Sentence denotes All patients had peripheral ground-glass opacities and/or lung consolidations in more than two pulmonary lobes.
T10 812-918 Sentence denotes Lung lesions were characterized by a high 18F-FDG uptake and there was evidence of lymph node involvement.
T11 919-1021 Sentence denotes Conversely, disseminated disease was absent, a finding suggesting that COVID-19 has pulmonary tropism.
T12 1023-1034 Sentence denotes Conclusions
T13 1035-1299 Sentence denotes Although 18F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our pilot data shed light on the potential clinical utility of this imaging technique in the differential diagnosis of complex cases.
T14 1301-1468 Sentence denotes An outbreak of acute respiratory disease caused by a novel coronavirus of zoonotic origin (SARS-CoV-2) occurred during December 2019 in Wuhan, Hubei province of China.
T15 1469-1570 Sentence denotes Additional cases have been subsequently identified both in other parts of China and worldwide [1, 2].
T16 1571-1639 Sentence denotes World Health Organization officially names the disease COVID-19 [3].
T17 1640-1754 Sentence denotes Common clinical manifestations of COVID-19 include fever, cough, shortness of breath, myalgia, and fatigue [4, 5].
T18 1755-1868 Sentence denotes Although detection of viral RNA remains the gold standard for diagnosis, false-negative results are not uncommon.
T19 1869-2098 Sentence denotes The possible reasons may include the lack of standard operation procedures (SOPs) and validation across different laboratories for viral identification, different viral loads at different anatomical sites and high mutation rates.
T20 2099-2424 Sentence denotes Consequently, clinical diagnosis is generally based on exposure history, clinical symptoms, results of blood and biochemical tests, and findings on chest computed tomography (CT)—which typically consist of ground-glass opacities (GGOs) or bilateral pulmonary consolidations in multiple lobular and sub-segmental areas [4, 6].
T21 2425-2623 Sentence denotes In general, the identification of pulmonary GGOs or patients presenting with persistent fever should prompt additional diagnostic testing for differential diagnosis—including 18F-FDG PET/CT imaging.
T22 2624-2886 Sentence denotes Here, we report the 18F-FDG PET/CT findings from four patients who were admitted to the Wuhan Union Hospital with lung GGOs and fever between January 13 and January 20, 2020—when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown.
T23 2887-3055 Sentence denotes A retrospective review of the patients’ medical history, clinical and laboratory data, as well as imaging findings (Table 1) strongly suggested a diagnosis of COVID-19.
T24 3056-3135 Sentence denotes Table 1 General characteristics and PET/CT findings of four cases with COVID-19
T25 3136-3158 Sentence denotes Patient number 1 2 3 4
T26 3159-3182 Sentence denotes Sex Man Man Woman Woman
T27 3183-3205 Sentence denotes Age, years 57 56 61 48
T28 3206-3335 Sentence denotes Clinical symptoms Fever, sore throat Fever, fatigue, dizziness Back pain, dry cough Fever, chill, dry cough, myalgia, and fatigue
T29 3336-3379 Sentence denotes History of staying in Wuhan Yes Yes Yes Yes
T30 3380-3451 Sentence denotes WBC (× 109/L) (reference range 3.5–9.5 × 109/L) Normal 3.33 3.47 Normal
T31 3452-3519 Sentence denotes Lymphocytes (%) (reference range 20–40%) Normal 17.5% Normal Normal
T32 3520-3588 Sentence denotes HsCRP (mg/L) (reference range 0–5 mg/L) 6.65 23.6 Not available 12.2
T33 3589-3652 Sentence denotes Respiratory pathogens* Negative Negative Not available Negative
T34 3653-3756 Sentence denotes PET/CT findings Number of affected lobes 2 (RUL, LLL) 5 (all lobes) 3 (RUL, RLL, LLL) 3 (RML, RLL, LLL)
T35 3757-3853 Sentence denotes Lung CT features GGO GGO and consolidative opacities GGO GGO with interlobular septal thickening
T36 3854-3877 Sentence denotes SUVmax 4.6 7.9 12.2 9.3
T37 3878-4035 Sentence denotes LN involvement Absent Right subclavian region, mediastinum Right supraclavicular region, mediastinum Right subclavian region, mediastinum, right hilar region
T38 4036-4057 Sentence denotes LN SUVmax – 7 5.4 5.5
T39 4058-4108 Sentence denotes Concomitant diseases** Absent Absent Absent Absent
T40 4109-4164 Sentence denotes *The following respiratory pathogens were investigated:
T41 4165-4285 Sentence denotes Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus, and Coxsackie B-virus specific IgM
T42 4286-4340 Sentence denotes **Including malignancies and other infectious diseases
T43 4341-4597 Sentence denotes WBC, white blood cell; hsCRP, high-sensitivity C-reactive protein; LN, lymph node; RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; GGO, ground-glass opacities; SUV, standardized uptake value
T44 4599-4605 Sentence denotes Case 1
T45 4606-4706 Sentence denotes A 57-year-old man living in Wuhan presented with sore throat and fever (39.0 °C) lasting for 3 days.
T46 4707-4900 Sentence denotes Laboratory testing revealed a white blood cell (WBC) count within the reference range and a slight elevation of high-sensitivity C-reactive protein (hsCRP; 6.65 mg/L, reference range 0–5 mg/L).
T47 4901-5101 Sentence denotes A search for common respiratory pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus, and Coxsackie B-virus specific IgM, yielded negative results.
T48 5102-5321 Sentence denotes A chest CT scan conducted in another hospital 2 days before revealed the presence of a GGO in the right lung, which required further diagnostic workout (differential diagnosis between a tumor and an infectious disease).
T49 5322-5503 Sentence denotes 18F-FDG PET/CT identified peripheral GGOs with an increased 18F-FDG uptake (SUVmax range 2.2–4.6) in the right upper lung (Fig. 1a, b, arrows) and left lower lung (Fig. 1c; arrows).
T50 5504-5569 Sentence denotes Unfortunately, SARS-CoV-2 nucleic acid testing was not performed.
T51 5570-5677 Sentence denotes Antiviral, anti-inflammatory, and symptomatic treatment for 2 weeks led to complete resolution of symptoms.
T52 5678-5777 Sentence denotes Fig. 1 Peripheral GGOs with an increased 18F-FDG uptake in the right upper lung and left lower lung
T53 5779-5785 Sentence denotes Case 2
T54 5786-6085 Sentence denotes A 56-year-old man with a recent history of surgery for lung repair and rib fracture internal fixation following a traumatic event presented to hospital with an 8-day history of intermittent fever (up to 39.1 °C, more frequent in early morning and the afternoon) accompanied by fatigue and dizziness.
T55 6086-6126 Sentence denotes Cough and sputum production were absent.
T56 6127-6296 Sentence denotes Laboratory testing revealed mild leukopenia (WBC count 3.33 × 109/L; reference range 3.5–9.5 × 109/L) with 75.5% neutrophils and 17.5% lymphocytes (normal range 20–40%).
T57 6297-6507 Sentence denotes Inflammatory indices, including hsCRP (23.6 mg/L) and erythrocyte sedimentation rate (73 mm/h; reference range < 15 mm/h), were increased, but a search for known respiratory pathogens yielded negative findings.
T58 6508-6671 Sentence denotes 18F-FDG PET/CT imaging (January 13, 2020) revealed multiple FDG-positive GGOs and consolidative opacities in both lungs (SUVmax range 1.8–7.9; Fig. 2a, b, arrows).
T59 6672-6803 Sentence denotes There were also multiple FDG-avid lymph nodes in the mediastinum and the subclavian region (SUVmax range 4.1–7.0; Fig. 2c, arrows).
T60 6804-6869 Sentence denotes Unfortunately, SARS-CoV-2 nucleic acid testing was not performed.
T61 6870-7048 Sentence denotes The lesions on 18F-FDG PET/CT were smaller than those detected on previous CT imaging (January 7, 2020) and regressed further after treatment (January 21, 2020; Fig. 2d, arrows).
T62 7049-7210 Sentence denotes Fig. 2 Multiple FDG-positive GGOs and consolidative opacities in both lungs as well as multiple FDG-avid lymph nodes in the mediastinum and the subclavian region
T63 7212-7218 Sentence denotes Case 3
T64 7219-7305 Sentence denotes A 61-year-old woman living in Wuhan complained of back pain and dry cough over a week.
T65 7306-7371 Sentence denotes Laboratory testing revealed a mild leucopenia (WBC 3.47 × 109/L).
T66 7372-7544 Sentence denotes Chest CT identified an 8-mm light shadow in the right upper lung lobe and a 9-mm solid nodule in the left lower lung lobe, which initially led to a suspicion of malignancy.
T67 7545-7685 Sentence denotes A week thereafter, 18F-FDG PET/CT revealed multiple peripheral FDG-avid GGOs (SUVmax range 3.7–12.2) in the right lung (Fig. 3a, b, arrows).
T68 7686-7832 Sentence denotes Multiple FDG-positive lymph nodes were also identified in the mediastinum and the right subclavian region (SUVmax range 3.4–5.4; Fig. 3c, arrows).
T69 7833-7884 Sentence denotes We did not perform SARS-CoV-2 nucleic acid testing.
T70 7885-7975 Sentence denotes An 18-day treatment with antiviral and anti-inflammatory drugs led to symptom improvement.
T71 7976-8117 Sentence denotes Fig. 3 Multiple peripheral FDG-avid GGOs in the right lung and multiple FDG-positive nodes in the mediastinum and the right subclavian region
T72 8119-8125 Sentence denotes Case 4
T73 8126-8289 Sentence denotes A 48-year-old woman working in the Wuhan Union Hospital presented with an 8-day history of fever (37–38 °C) accompanied by chills, dry cough, myalgia, and fatigue.
T74 8290-8379 Sentence denotes WBC count was within the reference range, but she had increased hsCRP levels (12.2 mg/L).
T75 8380-8447 Sentence denotes A search for known respiratory pathogens yielded negative findings.
T76 8448-8567 Sentence denotes Chest CT imaging (January 15, 2020, Fig. 4d) led to the identification of a blurry shadow in the right lower lung lobe.
T77 8568-8763 Sentence denotes A subsequent 18F-FDG PET/CT scan (January 20, 2020) revealed the presence of peripheral FDG-avid GGOs with interlobular septal thickening in both lungs (SUVmax range 3.7–9.3; Fig. 4a, b, arrows).
T78 8764-8957 Sentence denotes When compared with previous chest CT results, there was evidence of disease progression as shown by a higher number of lesions, which were also characterized by an increased extent and density.
T79 8958-9090 Sentence denotes There were also multiple FDG-positive lymph nodes in the mediastinum and right hilar region (SUVmax range 3.8–5.5; Fig. 4c, arrows).
T80 9091-9251 Sentence denotes Real-time fluorescent polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2 nucleic acid yielded negative findings in two independent measurements.
T81 9252-9407 Sentence denotes A follow-up chest CT (February 1, 2020) performed after antiviral and anti-infective treatment revealed a significant improvement in the picture (Fig. 4d).
T82 9408-9569 Sentence denotes Fig. 4 Peripheral FDG-avid GGOs with interlobular septal thickening in both lungs and multiple FDG-positive lymph nodes in the mediastinum and right hilar region
T83 9571-9581 Sentence denotes Discussion
T84 9582-9811 Sentence denotes Because COVID-19 is believed to have an interpersonal human-to-human transmission [2], either home residence or a travel history to Wuhan—coupled with exposure to known or suspected cases—is paramount to raise clinical suspicion.
T85 9812-9963 Sentence denotes The clinical, laboratory, and imaging characteristics of the four patients described in the current report are consistent with a diagnosis of COVID-19.
T86 9964-10072 Sentence denotes Herein, we therefore describe for the first time the 18F-FDG PET/CT findings of four patients with COVID-19.
T87 10073-10262 Sentence denotes In accordance with previously published observations [5, 6], our cases were characterized by the presence of peripheral GGOs and/or consolidative opacities in more than two pulmonary lobes.
T88 10263-10321 Sentence denotes Notably, all of these lesions showed a high tracer uptake.
T89 10322-10503 Sentence denotes Although a bilateral involvement of the lung parenchyma can be observed in several benign and malignant lung diseases [7], tumors presenting as GGOs are unlikely to be FDG-avid [8].
T90 10504-10730 Sentence denotes The high tracer uptake that characterized COVID-19 pulmonary infections reflects a significant inflammatory burden, similar to that elicited by the Middle East respiratory syndrome or the H1N1 pandemic influenza virus [9, 10].
T91 10731-10904 Sentence denotes Although COVID-19 infections do not seem to be accompanied by lymphadenopathy [6], our 18F-FDG PET/CT findings revealed an increased nodal FDG uptake in three of four cases.
T92 10905-11123 Sentence denotes Although no obvious nodal enlargement was evident, our imaging data indicate for the first time that COVID-19 may cause lymphadenitis—in line with previous data obtained from non-human primates exposed to MERS-CoV [9].
T93 11124-11260 Sentence denotes Another interesting finding is that no disseminated lesions were evident in our patients—suggesting that COVID-19 has pulmonary tropism.
T94 11261-11614 Sentence denotes Although 18F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our current findings demonstrate that this imaging modality may play a complementary diagnostic role in COVID-19—especially at early stages when clinical symptoms are not specific and differential diagnosis is challenging.
T95 11615-11730 Sentence denotes Our case series is limited by the small sample size and the lack of molecular confirmation of SARS-CoV-2 infection.
T96 11731-11877 Sentence denotes However, only 30–50% of infected patients had positive test for SARS-CoV-2 nucleic acid on RT-PCR (Chinese Academy of Sciences; unpublished data).
T97 11878-12315 Sentence denotes High rates of false-negative findings may be explained by several reasons, including (1) the lack of SOPs for SARS-CoV-2 nucleic acid detection, differences in sample handling, storage, and processing, (2) disease stages and different viral loads according to anatomical site (e.g., alveoli versus upper respiratory tract), (3) the lack of independent validation of current testing, and (4) the potential high mutation rates of COVID-19.
T98 12316-12493 Sentence denotes In light of these limitations, some cases of COVID-19 in China are currently diagnosed on clinical, laboratory, and imaging grounds, without resorting to molecular confirmation.
T99 12494-12855 Sentence denotes These caveats notwithstanding, we show for the first time that (1) lung lesions of patients with COVID-19 pneumonia are characterized by high 18F-FDG uptake, (2) this condition is accompanied by nodal involvement detectable on 18F-FDG PET/CT imaging, and (3) there is no evidence of disseminated disease, indicating that COVID-19 may have specific lung tropism.
T100 12857-12933 Sentence denotes This article is part of the Topical Collection on Infection and inflammation
T101 12934-12950 Sentence denotes Publisher’s note
T102 12951-13069 Sentence denotes Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
T103 13071-13104 Sentence denotes Compliance with ethical standards
T104 13106-13126 Sentence denotes Conflict of interest
T105 13127-13186 Sentence denotes The authors declare that they have no conflict of interest.
T106 13188-13240 Sentence denotes Research involving human participants and/or animals
T107 13241-13438 Sentence denotes This retrospective study of existing patient data and images was approved by the institutional review board of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.
T108 13439-13487 Sentence denotes The requirement for informed consent was waived.