18F-FDG brain PET hypometabolism in patients with long COVID

Abstract

Purpose In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of 18 F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. Methods PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. Results In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). Conclusion This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE This article is part of the Topical Collection on Neurology

Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNA Covid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation

“…The Covid-19 pandemic has caused significant morbidity and mortality throughout the world, as well as major social and economic disruptions. In the field of nuclear medicine, some exciting imaging findings associated with Covid-19 were described [20][21][22][23].…”

About the source and consequences of 18F-FDG brain PET hypometabolism in short and long COVID-19

“…Moreover, it is known that astrocytes play pivotal roles in the brain defence against peripheral inflammatory changes [11]. Guedj and colleagues [1] mentioned that acute systemic inflammation and SARS-CoV-2 neurotropism could be related to brain inflammatory alterations. Complementary, other groups identified signs of reactive astrogliosis in postmortem tissue of COVID-19 patients [12], in cellular models and in brain organoids [13].…”

“…While the cellular origins of brain 1 8 F-FDG PET hypometabolism in COVID-19 remain to be defined, it seems clear that we are dealing with persistent synaptic dysfunction. Guedj et al [1] demonstrated that multiple brain regions are hypometabolic in long COVID. In addition, it seems that there is a link between clinical manifestations and regional glucose hypometabolism.…”

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We have read with great interest the article recently published by Guedj et al, titled 18 F-FDG brain PET hypometabolism in patients with long COVID [1]. We recently proposed that PET imaging versatility might hold the key for understanding pathophysiological changes in the brain of COVID-19 patients [2].

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Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information

“…136 One study comparing 35 Long COVID patients to 44 controls found significant hypometabolism in the brain, including the olfactory gyrus, right temporal lobe (including the hippocampus and amygdala), the bilateral pons/medulla brainstem, and the bilateral cerebellum; notably, the clusters of hypometabolism were correlated with patient symptoms, including hyposmia and anosmia, memory and cognitive impairment, pain, and insomnia. 137 There have also been additional suggestions that brainstem dysfunction might be involved in a variety of COVID-19 clinical manifestations. For instance, Yong 138 cites a number of autopsy studies to support this hypothesis.…”