Systematic Studies on Molecular Imaging in Cerebral Manifestations of COVID-19: Post–COVID-19 Syndrome
| Parameter | Guedj et al. (43) | Sollini et al. (45) | Morand et al. (44) | Dressing et al. (46) |
|---|---|---|---|---|
| Research question | Metabolic pattern of long COVID | Whole-body PET/CT (including brain) to gain insights into long COVID (for whole body, see report) | Regional metabolic pattern in pediatric patients with suspected long COVID | Regional metabolic pattern in patients with neurocognitive long COVID |
| Population | ||||
| Inclusion (main) | Retrospective; >3 wk after SARS-CoV-2 infection (PCR+ or antibody-positive); persistent fatigue; PET for neurologic complaints; normal CT/MRI | Observational case-control study; ≥1 persistent symptom for >30 d after infection (PCR: NA); NCs: age- and sex-matched, surgically treated melanoma pts with negative PET/CT | Retrospective; children with suspected long COVID (clinical diagnosis); evaluation for various functional complaints ≥ 4 wk after suspected SARS-CoV-2 infection | History of PCR+ SARS-CoV-2 infection; new subjective neurocognitive symptoms > 3 mo since PCR+; no preexisting neurodegenerative disease; PET recommended to all pts (performed in 14/31; clinical findings in PET subgroup not different) |
| n | 35 | 13 | 7 | 31 |
| Age (y) | 55 ± 11 | 54 (46–80) | 12 (10–13) | 14 (PET), 56 ± 7 |
| Selected clinical findings | Hospitalized in ICU (12/31); ventilated (5/31); memory/cognitive complaints (17), insomnia (16), hyposmia (10) | Hospitalization (7/13); ventilated (2/13); dyspnea (9), fatigue (8), anosmia (4), ageusia (3) | Initial symptoms: fever (6), muscle pain (6), asthenia (5), rhinitis (5), hyposmia (5); long COVID symptoms: fatigue (5), cognitive impairment (5), dyspnea (4), headache (4); PCR+ (1/5) and positive SARS-CoV-2 serology (2/6) | Acute-phase inpatients (10; ICU 4); no current focal sign; subjective difficulties in attention and memory (31), fatigue (24), reduced work quota/unable to work (12); extensive neuropsychology: normal on group level, unimpaired test battery (15), but individual pts with deficits in memory domain (7/31) or impaired MoCA (9/31), fatigue (19/31) |
| 18F-FDG PET | ||||
| Analysis | SPM: group; normalization: proportional scaling; comparison: 44 NCs (earlier study); P < 0.001, clusterwise P < 0.05 FWE | Brain PET extracted from whole-body scans; SPM: group; normalization: proportional scaling (global); comparison: 26 control patients; P < 0.001/0.005 (uncorrected) | SPM: group; normalization: proportional scaling (global); comparison: 21 pediatric control patients.; findings in adults (Guedj et al. (43)); P < 0.001, clusterwise P < 0.05 FWE | Single case: visual inspection plus single-case statistical analyses (3D-SSP); PCA: expression of COVID-19–related covariance pattern; SPM (confirmatory): group, normalization: brain parenchyma, P < 0.05 FDR; comparison: 45 control patients (Hosp et al., (18)) |
| Δt (wk) | 14 ± 4 (4–22) | 19 ± 4 | 20 (4–34) | 28 ± 9 |
| Major findings | DEC: rectal/orbital gyrus, R temporal lobe (incl. MTL), R thalamus, pons/medulla, CBL; various weak correlations (r2 < 0.35), e.g., complaints (n), hyposmia, memory/cognitive complaint vs. CBL DEC | DEC (group contrast, P < 0.001)*: R parahippocampal, R thalamus; DEC in persistent anosmia/ageusia (P < 0.005)*: bilateral parahippocampal and orbitofrontal; DEC in persistent fatigue (P < 0.005)*: R parahippocampal, brain stem, bilateral thalamus | Comparison to pediatric control patients: bilateral DEC in MTL, pons, CBL; comparison to adult long COVID pts: no difference | Single case: no distinct pathologic finding; PCA: no elevated expression of COVID-19–related covariance pattern, no correlation with MoCA; SPM (confirmatory): no region of significantly different metabolism, no correlation with clinical scores |
| Hypothesis | SARS-CoV-2 neurotropism through olfactory bulb, extension of impairment to limbic or paralimbic regions, thalamus, CBL, and brain stem | Neuronal/synaptic dysfunction occurring after inflammatory changes triggered by SARS-CoV-2 infection | Several possible explanations (inflammatory, immune, neurotropism, vascular, gut–brain disturbance, psychologic), but none clearly favored | Factors other than those causing subacute cortical dysfunction in COVID-19 cause or contribute to symptoms in long COVID, in particular fatigue |
* Questionable anatomic localization, hard to differentiate from CSF spaces.
3D-SSP = three-dimensional stereotactic surface projection; PCR = polymerase chain reaction; NA = not applicable; NCs = healthy controls; pts = patients; ICU = intensive care unit; DEC = decreased signal; MTL = mesial temporal lobe; CBL = cerebellum; PCA = principal-components analysis; MoCA = Montreal Cognitive Assessment.
Numbers in parentheses refer to number of subjects with specified finding (if subsample assessed is smaller than study group, sample size as indicated). 18F-FDG target parameter is glucose metabolism.