key: cord-0893589-kf8486wm
authors: Gheysens, Olivier; Belkhir, Leïla; Jamar, François
title: Imaging in Post-COVID Lung Disease: Does (18)F-FDG PET/CT Have the Key?
date: 2022-02-03
journal: J Nucl Med
DOI: 10.2967/jnumed.121.263166
sha: 91584c9da3d243bcf72fc65277401c8dcd907ab3
doc_id: 893589
cord_uid: kf8486wm

nan

pain, headache, and cognitive symptoms up to 3-6 mo after diagnosis. Such persistent symptoms are more frequently reported after COVID-19 than after influenza infection.

However, this perspective will focus on subacute and chronic lung disease, referred to as PCLD. Five percent of COVID-19 survivors evolve to chronic respiratory failure, manifested by breathlessness, cough, or even oxygen needs (4) .

From the very beginning of the outbreak, multiple casuistic reports on 18 F-FDG PET/CT were published, without emphasis on the time course, since the initial observations focused either on the most acute phase in severely ill patients or on serendipitous findings in asymptomatic oncology patients. Several studies indicated a 2-to 4-fold increased incidence of interstitial pneumonia detected on 18 F-FDG PET/CT in the latter group during the early phase of the pandemic (5) . Other authors identified a relationship between the structural changes as assessed using the COVID-19 Reporting and Data System and metabolic changes (6) . Albeit informative, such reports did not take into account the temporal kinetics of the disease. It has become clear that 18 F-FDG PET/CT has a limited role, if any, in establishing the diagnosis of active COVID-19 infection. From a logistic viewpoint, organizing a PET/CT scan in a nuclear medicine department had more drawbacks than advantages, as compared with dedicated CT-scan suites, with a rapid turnover even with the implementation of all necessary hygiene measures. Several reports indicate that 18 F-FDG PET/CT results in the early phase of the disease were similar to those observed in the literature on pneumonia due to other aggressive viruses.

In this retrospective observational study, Thornton et al. were able to distinguish several temporal patterns in a limited number of subjects during the first 2 peaks of COVID-19. Using 18 F-FDG PET/CT, they not only studied the functional and morphologic pattern at different disease stages but also demonstrated the time relationship between these changes. In asymptomatic patients, without any history or suggestion of a COVID-19 diagnosis, the authors identified 2 distinct groups: one group of acute patients in the early stage (n 5 8) with typical ground-glass changes on CT and relatively low 18 F-FDG uptake (median SUV max , 1.6, and median target-to-background ratio [TBR lung ], 6.4, where the background refers to the lowest lung uptake) and a second group of acute patients in the late stage, with a more extensive consolidation pattern on CT and a significantly higher SUV max (median, 4.0) and TBR lung (median, 13.7) (P 5 0.001). SUV max was similar in a small series of convalescing patients reported by Bai et al., but these were patients recovering from severe infection (7) . Temporal data in the study of Thornton et al. were retrieved from the electronic health record system, with the inherent limitations of such a retrospective approach. Notwithstanding, the authors demonstrated a significant positive correlation between TBR lung and the estimated time since onset (Spearman r s 5 0.595, P 5 0.003). These findings are in keeping with the current pathophysiologic hypotheses of COVID-19 infection-that it first presents as a viral infection, with no or moderate symptoms and seemingly low 18 F-FDG uptake, and then is followed by an acute immune response, endothelial activation and inflammation, and variable levels of immune cell infiltration (including neutrophils, lymphocytes, and monocyte-macrophages), as well as angiogenesis. This second phase, characterized by the presence of many glucose-avid cells, is responsible for the increased 18 F-FDG uptake. However, the responsible mechanisms of PCLD are not well understood and are probably numerous and intertwined as reflected by the wide diversity of the symptoms. The main hypotheses include a persisting chronic inflammatory process or a dysregulated immune phenomenon (8) .

Although the study by Thornton et al. illustrates the temporal changes in 18 F-FDG PET/CT patterns, it does not provide information on the severity of the disease because of the lack of clinical outcome data, as stated by the authors in their conclusions.

Nevertheless, in the group of 18 patients with PCLD, a condition that has hardly been studied with 18 F-FDG PET/CT, a higher SUV max (median, 5.8) was observed in patients who had not been treated with high-dose steroids for at least 10 d. Conversely, patients treated with steroids after discharge had a lower SUV max (median, 2.4) and TBR lung (median, 6.6 under steroids, vs. 18.1 without steroids), like those observed in the early stage of the acute phase. The RECOV-ERY study clearly demonstrated the benefit of 6 mg of dexamethasone in oxygen-dependent or ventilated patients with a lower 28-d mortality (9) . To our knowledge, little is known about the benefit to pulmonary function and survival over the long term. In addition, an observational study by Myall et al. including 35 patients with lung functional deficit beyond 6 wk after the acute phase (due to interstitial disease and organizing pneumonia) demonstrated a morbidity benefit, defined by improvement in lung functional tests, in the 30 patients treated with steroids (4). Furthermore, a recent report on long COVID demonstrated not only increased residual lung 18 F-FDG uptake (with similar SUV max data) but also evidence of multisystemic inflammation (10) .

From the published data and long-COVID-19 perspectives, it may be wise to envision that metabolic imaging with 18 F-FDG PET/CT may help identify patients with persistent symptoms after 6-12 wk, for whom additional therapy with, for example, corticosteroids could be proposed. This possibility is in keeping with previous observations that increased 18 F-FDG uptake in chronic interstitial lung disease of other etiologies was reported as a marker of evolution toward lung fibrosis and poor prognosis. At this stage, there is no evidence that such imaging may be justified, nor is information available on the optimal timing and dosing of steroids. Therefore, it is worth challenging this issue with, for instance, a 2-arm randomized study in which all patients with persistent pulmonary symptoms beyond 6 wk of a negative PCR test would undergo 18 F-FDG PET/CT upfront but in which the interpreters would be masked to patient data before randomization. Patients could then receive either corticosteroids or placebo, and as the outcome, the clinical benefit results would be correlated with the 18 F-FDG PET/CT results. In conclusion, although it is agreed that 18 F-FDG PET/CT has little role in diagnosing COVID-19 as such, its potential role in the later phases of the disease must be considered. Whether 18 F-FDG PET/CT can help identify patients who will develop a severe or even dramatic course of lung fibrosis remains to be determined: prospective and, when possible, randomized therapeutic trials with masking of the 18 F-FDG PET/CT results would be extremely helpful.

No potential conflict of interest relevant to this article was reported.

Evolution of 18 F-FDG PET/CT findings in patients after COVID-19: an initial investigation

Persistent symptoms in patients after acute COVID-19

Managing the long term effects of covid-19: summary of NICE, SIGN and RCGP rapid guideline

Persistent post-COVID-19 interstitial lung disease: an observational study of corticosteroid treatment

Increased incidence of interstitial pneumonia detected on [ 18 F]-FDG-PET/CT in asymptomatic cancer patients during COVID-19 pandemic in Lombardy: a casualty or COVID-19 infection

Incidental findings suggestive of COVID-19 pneumonia in oncological patients undergoing 18

PET/CT studies: association between metabolic and structural lung changes

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

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Dexamethasone in hospitalized patients with Covid-19

Long COVID hallmarks on [ 18 F]FDG-PET/CT: a case-control study