Nursing Home Physician with Normal Chest X-Ray and Probable COVID-19 Based on 18F-Fluorodeoxyglucose PET/CT Imaging.

To the Editor:

We report the clinical, laboratory, and imaging studies of a 75‐year‐old physician with a history of lymphoma who cared for coronavirus disease 2019 (COVID‐19) patients in a nursing home and subsequently developed systemic and laboratory findings consistent with probable COVID‐19 with minimal respiratory symptoms. Two reverse transcriptase–polymerase chain reaction (RT‐PCR) tests for the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid and his chest X‐ray were negative. During hospitalization, a clinical diagnosis of COVID‐19 was finally confirmed based on findings suspicious for COVID‐19 on 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) imaging. The rationale for utilizing 18F‐FDG PET/CT in suspected COVID‐19 patients with a normal chest X‐ray and selected comorbid neoplastic conditions with minimal or no respiratory symptoms and signs and the role of 18F‐FDG PET/CT in elucidating the pathophysiology of COVID‐19 are discussed.

HISTORY

During 5 days before hospital admission, he self‐quarantined with fever, headache, myalgias, anorexia, low back pain, and ageusia, with minimal cough and shortness of breath. A nasopharyngeal swab tested by RT‐PCR was negative for SARS‐CoV‐2, other coronaviruses, and respiratory viruses, including influenza A and B. His oxygen saturation was greater than 95% on room air. Because of progressive anorexia, dehydration, and weakness, he was admitted to a New York City hospital with a temperature of 39°C, blood pressure of 143/91 mmHg, heart rate of 109 beats per minute, respiratory rate of 18 breaths per minute, and O2 saturation of 95% on room air. Table 1 provides laboratory findings. A second nasopharyngeal swab was negative for SARS‐CoV‐2, other coronaviruses, and a respiratory pathogen PCR panel. Because of persistent fevers and his history of lymphoma, an 18F‐FDG PET/CT scan from skull base to thigh was performed. It revealed bilateral FDG‐avid peripheral ground‐glass opacities (GGOs), multilobe consolidations, and FDG‐avid thoracic nodes suspicious for COVID‐19–related infectious process (Figure 1). He was treated with intravenous hydration, low‐molecular‐weight heparin, antipyretics, and bed rest and discharged afebrile to home after a 5‐day hospitalization to self‐isolate and eventually return to work.

Table 1.

Relevant Hospital Diagnostic Test Results

Test	Result	Reference Range
White blood cell count, ×103/μL	3.6	3.4–11.2
Total lymphocyte count, ×103/μL	0.7	1.0–4.8
Platelet count, ×103/μL	146	150–450
Prothrombin time, s	12.8	9.5–12.5
Partial thromboplastin time, s	37.6	27.6–36.6
Erythrocyte sedimentation rate, mm/h	48	0–20
C‐reactive protein, mg/dL	11	<0.9
High‐sensitivity C‐reactive protein, mg/L	68.66	<3.00
Lactate dehydrogenase, U/L	322	118–230
Troponin, ng/mL	<0.03	<0.04
Lactate, mmol/L	1.50	0.50–2.20
Ferritin, ng/mL	1,276	22–322
D‐dimer, ng/mL	792	0–229
Fibrinogen, mg/dL	541	180–400
Interleukin 6, pg/mL	11	<5
Procalcitonin, ng/mL	0.06	<0.08
Albumin, g/dL	2.7	3.2–4.8
Respiratory pathogen PCR panel a	None detected	None detected

Abbreviation: PCR, polymerase chain reaction.

Respiratory pathogen PCR panel included severe acute respiratory syndrome coronavirus 2, other coronaviruses, adenovirus, metapneumovirus, rhinovirus/enterovirus, influenza A and B, parainfluenza 1, 2, 3, and 4, respiratory syncytial virus, Bordetella pertussis, chlamydia pneumonia, mycoplasma, and Bordetella parapertussis.

Figure 1.

(A) Axial computed tomographic (CT) image through the thorax, showing left upper lobe peripheral ground‐glass opacity (GGO) (thick arrow) and left lower lobe peripheral GGO (thin arrow). (B) Fused axial positron emission tomography/CT image at the level of the carina, showing left upper lobe fluorodeoxyglucose (FDG)‐avid peripheral GGO (thick arrow) and left lower lobe FDG‐avid peripheral GGO (thin arrow). R, right.

LITERATURE REVIEW

Four hospitalized adult patients with respiratory symptoms highly suspected of having COVID‐19 in Wuhan, China, had chest CT scan findings of GGOs and/or lung consolidations in more than two pulmonary lobes. Admission chest X‐rays were not performed, as was the standard in suspected COVID‐19 cases. Subsequent 18F‐FDG PET/CT identified peripheral FDG‐avid lesions consistent with a significant inflammatory burden similar to that seen in Middle East respiratory syndrome or the H1N1 pandemic influenza virus. Three of the four showed evidence of lymph node involvement suggestive of lymphadenitis. Despite the fact that RT‐PCR for the detection of SARS‐CoV‐2 nucleic acid testing was not performed in three cases and was negative twice in one case (as in this case), all four of these cases had a clinical presentation, course, laboratory results, and imaging studies strongly suggestive of a diagnosis of COVID‐19. Czemin et al reported an asymptomatic 53‐year‐old patient referred for restaging of a pancreatic neuroendocrine tumor with 18F‐FDG PET/CT that showed hypermetabolic regions in two lobes, correlating with GGOs. COVID‐19 infection was subsequently confirmed. Polverari et al reported a case of 18F‐FDG/CT imaging in an asymptomatic 73‐year‐old male referred for evaluation of solitary lung nodule found on CT scan performed 4 years after resection for a non–small‐cell lung cancer. Findings were consistent with GGOs and increased uptake in mediastinal and right paratracheal nodes. Subsequent testing with RT‐PCR was positive for SARS‐CoV‐2.

DISCUSSION

This case highlights the findings on 18F‐FDG PET/CT in a nursing home physician suspected of COVID‐19, raises a number of clinical dilemmas, and points to the potential use of PET/CT in studying the pathophysiology of COVID‐19 as follows:

Our patient had two negative RT‐PCR tests for SARS‐CoV‐2, confirming the high false‐negative rate when compared with CT imaging. A review of seven previously published studies of both inpatients and outpatients with SARS‐CoV‐2 infection reported a wide variation in sensitivity of RT‐PCR, depending on the time the test was taken after symptom onset. Specifically, the false‐negative rate of RT‐PCR tests was 38% on the day of symptom onset, 20% 3 to 4 days after symptom onset, and 66% 2 weeks after symptom onset. Other factors that could contribute to the two negative RT‐PCR tests include sampling, storage, and processing errors and different viral loads, depending on stage of the disease. Most important, the sensitivity of chest CT for diagnosing COVID‐19 has been shown to be 98% compared with 71% for RT‐PCR.

The 18F‐FDG PET/CT findings in this patient are consistent with past studies showing multiple, bilateral FDG‐positive GGOs, multilobar consolidations, and evidence of lymph node involvement.

GGOs are often unperceivable on chest radiography, particularly in patients with few symptoms or low severity. Although we are not suggesting that routine 18F‐FDG PET/CT scans be done on patients suspected of COVID‐19, we believe the standard of care should be that patients with a clinical syndrome including respiratory symptoms and/or signs consistent with COVID‐19, a negative chest X‐ray, and neoplastic comorbidities have a chest CT scan. Bilateral GGOs or consolidation on chest CT scan in the proper clinical situation should prompt the radiologist to suggest COVID‐19 as a possible diagnosis.

Findings consistent with COVID‐19 will be found in patients having 18F‐FDG PET/CT for either staging or recurrence of malignancies. Consequently, nuclear medicine departments and staff need to assume that all patients undergoing 18F‐FDG PET/CT need to be screened before scanning, personnel properly gowned and masked, the facility properly cleaned and disinfected afterwards, and lung nodule evaluation be modified.

FDG PET/CT is highly sensitive for detecting inflammatory disease and is a potential modality to study the inflammatory components of SARS‐CoV‐2 infections, monitoring disease progression and treatment effects and potentially improving patient management. In addition, FDG PET/CT may elucidate cytokine storm, focusing not only on pulmonary inflammation but also other organs that have been reported to be involved (i.e., myocardium, pericardium, and intestine).