Background: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients. In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. Methods: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. Findings: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. Interpretation: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.

J. Neurochem. (2008) 104, 1553–1564. Abstract Conversion of the native, predominantly α‐helical conformation of prion protein (PrP) into the β‐stranded conformation is characteristic for the transmissible spongiform encephalopathies such as Creutzfeld–Jakob disease. Curcumin, an extended planar molecule and a dietary polyphenol, inhibits in vitro conversion of PrP and formation of protease resistant PrP in neuroblastoma cell lines. Curcumin recognizes the converted β‐form of the PrP both as oligomers and fibrils but not the native form. Curcumin binds to the prion fibrils in the left‐handed chiral arrangement as determined by circular dichroism. We show that curcumin labels the plaques of the brain sections of variant Creutzfeld–Jakob disease cases and stains the same structures as antibodies against the PrP. In contrast to thioflavin T, curcumin also binds to the α‐helical intermediate of PrP present at acidic pH at stoichiometry of 1 : 1. Congo red competes with curcumin for binding to the α‐intermediate as well as to the β‐form of PrP but is toxic and binds also to the native form of PrP. We therefore show that the partially unfolded structural intermediate of the PrP can be targeted by non‐toxic compound of natural origin.

The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Sträussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [18F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer's disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD.

Deposition of conformationally altered proteins prominently characterizes pathogenesis and pathomorphology of a number of neurodegenerative disorders. 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile ([F-18]FDDNP), a hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent imaging probe has been used with positron emission tomography to visualize brain pathology in the living brain of Alzheimer disease (AD) patients. Its non-radiofluorinated analog FDDNP was shown to label senile plaques and neurofibrillary tangles (NFTs) in brain tissue sections. This work aimed at evaluating FDDNP labeling of various protein deposits in fixed, paraffin-embedded brain tissue sections of selected neurodegenerative disorders: AD, cerebral amyloid angiopathy (CAA), transmissible spongiform encephalopathies, progressive supranuclear palsy (PSP), Pick disease (PiD), Parkinson disease, dementia with Lewy bodies, multiple system atrophy (MSA). Cerebral hypertensive vascular hyalinosis (HVH) was used as negative control. Significant agreement between amyloid histochemical properties and FDDNP labeling of the deposits was established. FDDNP labeling showed high positive predictive value for birefringence in senile plaques and NFTs in AD, prion plaques and amyloid deposits in CAA. No FDDNP labeled structures were observed in HVH, PSP, PiD or MSA tissue sections. Our findings may be of significant value for the detection of neuropathological aggregates with [F-18]FDDNP in some of these disorders in the living brain of human subjects.