Diagnosis of COVID-19 pneumonia in asymptomatic patients after an oncological PET/CT

Abstract

Introduction

On January 30, 2020, the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus. There are some oncological indications that have special priority and studies are still being carried out despite the current situation. In these studies we have found suspicious findings of COVID-19 pneumonia in asymptomatic patients. The objective of this work is to assess the incidence of these findings, describe their characteristics and the evolution of suspected patients.

Material and methods

Oncological PET studies carried out in asymptomatic patients between March 18 and April 8, 2020 have been reviewed. Patients who presented findings suggestive of corresponding to an pulmonary infectious process were selected. Clinical findings have been reviewed to confirm or rule out SARS-CoV2 infection.

Results

During the specified period, a total of 129 PET-CT studies were performed. Of these, 11 (8.5%) found suspicious findings of a pulmonary infectious process. These were 8 men and 3 women aged between 30 and 79 years (mean 62.2).

Conclusions

Patients with COVID 19 can present few symptoms of the disease, and in PET-CT studies both presymptomatic and almost asymptomatic patients can be detected, so nuclear medicine physicians should take special attention to the pulmonary evaluation of PET-CT studies.

Resumen

Introducción

El 30 de enero de 2020 la organización mundial de la salud (OMS) declaró una emergencia internacional por la pandemia causada por un nuevo coronavirus. Existen algunas indicaciones oncológicas que tienen especial prioridad y se siguen realizando estudios a pesar de la situación actual. En estos estudios hemos encontrado hallazgos sospechosos de neumonía COVID-19 en pacientes asintomáticos. El objetivo de este trabajo es valorar la incidencia de estos hallazgos, describir sus características y valorar la evolución de los pacientes sospechosos.

Material y métodos

Se han revisado los estudios PET oncológicos realizados entre el 18 de marzo y el 8 de abril de 2020. Se han identificado los pacientes que presentaban hallazgos sugerentes de corresponder con un proceso infeccioso pulmonar de forma incidental en pacientes asintomáticos. Se han revisado las historias clínicas de estos pacientes para confirmar o descartar la infección por SARS-CoV2

Resultados

Durante el periodo especificado se realizaron un total de 129 estudios PET-TC con indicación oncológica. De ellos, en 11 (8,5%) se encontraron hallazgos sospechosos de proceso infeccioso pulmonar. Se trataba de 8 varones y 3 mujeres con edades comprendidas entre los 30 y los 79 años (media 62,2).

Conclusiones

Los pacientes con COVID 19 pueden presentar escasos síntomas de la enfermedad, y en los estudios PET-TC se pueden detectar tanto pacientes presintomáticos como pacientes casi asintomáticos por lo que los médicos nucleares deben prestar especial atención en la valoración pulmonar de los estudios PET-TC.

Introduction

On January 30, 2020 the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]).¹ Infection by this coronavirus causes the COVID-19 coronavirus disease which is a respiratory tract infection involving fever, cough and radiographic alterations. The virus produces severe pneumonia with respiratory distress, placing the lives of patients at risk.² The mean incubation period is 5–6 days, although this may vary greatly (from 0 to 24 days).³ The mean time from symptom onset to recovery is of 2 weeks, if the involvement is mild, and from 3 to 5 weeks in cases of severe disease. In the analysis of the outbrreak in China, the WHO suggested that asymptomatic cases were of little relevance in the expansion of the pandemic. However, clusters of patients in which the index case was asymptomatic have been described⁴ and in other cases, it is asumed that the index case was in a presymptomatic period.⁵ Proportions of transmission by presymptomatic patients have been estimated as being as high as 62%.⁶

At present, definitive diagnosis of infection by SARS-CoV-2 is obtained by polymerase chain reaction (PCR) used to detect the virus in samples usually obtained from the upper respiratory tract. The diagnosis also includes the history of exposure, clinical symptoms and the results of imaging tests. The most frequent alterations are bilateral ground glass opacities in several pulmonary subsegments. The alerations are evident on chest X-ray in 59% of the cases and in computerized tomography (CT) in 89% of the cases.⁷

Most health care activities in Nuclear Medicine Departments can be postponed. However, some oncological indications have special priority and continue to be carried out despite measures of lockdown and social distancing. On some occasions, delay in imaging studies without an estimation of a study date may be more harmful to patients than the risk assumed by attending the hospital to undergo the study. Therefore, in our center, some positron emission tomography/CT (PET/CT) oncological studies have continued to be performed after individual evaluation of the cases in patients who are asymptomatic from a respiratory point of view.

In these studies we have detected findings suspicious of COVID-19 pneumonia in asymptomatic patients. The aim of this study was to evaluate the incidence of these findings, describe their characteristics and assess the evolution of patients suspected of having COVID-19.

Material and methods

We reviewed the oncological PET studies performed from March 18 to April 8, 2020 in our center. Patients presenting incidental findings suggestive of an infectious pulmonary process in asymptomatic patients were identified. The clinical histories of these patients were reviewed to confirm or rule out infection by SARS-CoV-2 and to determine their evolution.

The PET/CT studies were performed according to the usual protocol. During the state of alarm of the pandemic protection measures were enforced for both patients and professionals during the study acquisitions. Masks were used, hands were washed after contact with the patients and the equipment was cleaned after each study. After a 6 h fasting period between 300 and 450 MBq of ¹⁸F-FDG were injected into the patients after establishing that glycemia values were less than 200 mg/dl. After a rest period of 50−60 min, the PET/CT acquisition was begun in Siemens Biograph 6 equipment. The acquisition was performed from the cranial vertex to the proximal third of the lower extremities. A free-breathing CT protocol was performed with 110 kV and 85 mAs with dose modulation (CareDose®). Afterwards, the PET study was acquired with a duration of 3 min per bed position.

Results

During the study period, a total of 129 PET/CT studies for oncological indication were performed. Of these, 11 (8.5%) showed suspicious findings of an infectious pulmonary process in 8 men and 3 women of 30–79 years of age (mean: 62.2).

In 4 of the cases there was a single infiltrate with ground glass density which had newly appeared or was previously unknown (Fig. 1). The remaining 7 cases presented multiple bilateral ground glass infiltrates (Fig. 2). Mild FDG uptake was observed in the infiltrates in all the cases. One of the cases also presented known pulmonary fibrosis. None of the patients presented significant mediastinal adenopathies. In all the cases the physician requesting the PET/CT was informed of the suspicion of COVID-19.

Fig. 1.

Axial slice of CT, PET/CT, PET and maximum intensity projection image of 52-year-old male patient underoing study for staging of recently diagnosed gastric cancer. A ground glass infiltrate is shown in the middle lobe. In the days following the study the patient developed fever and cough. He remained confined at home. PCR was not performed.

Fig. 2.

Axial slice of CT, PET/CT, PET and maximum intensity projection (MIP) image of a 63-year-old male patient who underwent the study for suspicion of recurrence of cancer of the larnyx. Several areas of ground glass density with FDG uptake are observed. A thyroid lesion can also be observed in the MIP image. The patient was admitted for study. The PCR study was positive, and on questioning the patient he only reported mild hyporexia and ageusia. The day after the study, blood analysis showed lymphophenia, and an increase in C reactive protein and d-dimer levels. The patient did not present cough, fever or gastrointestinal symptoms and was discharged after 3 days, with the recommendation of home confinement.

Of the 4 patients with a single infiltrate, one was not followed, another underwent PCR with a negative result and has not shown any respiratory clinical manifestations. The other 2 presented symptoms of dry cough and fever in one without alteration of the general status and the other only presented ageusia. Both underwent home confinement. The initiation of therapy was proposed (chemotherapy in one case and surgery in the other), and to date, PCR has not been performed (19 and 22 days after the PET study).

Of the 7 patients with multiple bilateral infiltrates, 5 (71%) were confirmed by PCR. Two of these patients, who showed the most extensive involvement, developed manifestations of infection in the days following the study, consisting of fever, cough, general malaise and dyspnea and died due to the pneumonia process at 7 and 12 days after the study. Two had presented fever between 2 and 3 weeks prior to the study and one presented mild clinical manifestations the week after the study. Two of the cases with multiple bilateral infiltrates were PCR negative; one developed mild clinical manifestations and analytical alterations (lymphophenia, elevation of d-dimers) and the other was admitted with manifestations of dyspnea and suspicion of COVID-19, despite a negative PCR result. In both cases the clinical suspicion of COVID-19 pneumonia persists.

Discussion

Some clinical indications require PET/CT studies despite lockdown measures and social distancing enforced by the government.⁸ Since the beginning of the pandemic, the capacity of PET/CT to detect pulmonary alterations caused by COVID-19 has been reported.⁹ During these weeks several clinical cases of patients who were incidentally diagnosed during a PET/CT study have been published.¹⁰ Recently, a series of cases of patients diagnosed with COVID-19 during oncological PET studies in an area with a high incidence of contagion have been published with similar results to those of the present study.¹¹

Almost one out of 10 asymptomatic patients who have undergone an oncological PET study present findings suggestive of COVID-19 pneumonia. On one hand, this confirms the justification of the use of strong hygienic measures with all patients (hand washing, use of gloves, mass, cleaning of equipment and patient zones), while on the other hand, nuclear medicine physicians must remain alert to pulmonary findings, especially during these weeks, since these patients are often close to initiating surgical or systemic treatments, which may be complicated by a severe infectious process.

Despite being diagnosed when presymptomatic, 2 of our patients died of pneumonia; one presented a previous severe pulmonary disease and the other presented clinical manifestations which evolved rapidly. It was of note that 2 of the patients had presented a self-limiting febrile episode 2 weeks before the PET/CT study, both being confirmed by PCR but did not later develop clinical manifestations, showing a practically asymptomatic evolution of the process. In our experience, it seems that postponement of the initiation of therapy is indicated, even in paitents with negative PCR results, provided that the evolution of the disease is not at risk.

Conclusion

Patients with COVID-19 may present scarce symptoms of the disease, and PET/CT studies can detect both presymptomatic and asymptomatic patients. Therefore, special attention should be given to pulmonary evaluation in PET/CT studies.

Conflict of interests

The authors declare no conflict of interests.