Persistent dyspnea in post-COVID patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

Aim/Introduction: While there's a wide literature on Computed Tomography (CT) abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy has been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism (PE), presenting persistent dyspnea (post-COVID). We compared perfusion scintigraphy and CT findings of post-COVID patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (non-COVID). The correlation between lung perfusion scintigraphy findings and 1) CT abnormalities and 2) clinical/biochemical parameters were also assessed. Material(s) and Method(s): 18 post-COVID and 20 non-COVID patients who underwent lung perfusion scintigraphy and chest high-resolution CT for dyspnea from March 2020 to April 2022 were retrospectively enrolled. From lung perfusion scintigraphy images, counting rates for upper, middle, and lower fields were normalized for the total lung counts to calculate the corresponding ratios (UTR, MTR, and LTR, respectively). CT images were analyzed using a semiautomated segmentation algorithm of 3DSlicer (www.slicer. org), obtaining total, emphysematous, infiltrated and collapsed volumes, normalized for the total lung volumes. Similarly, blood vessel's volumes were collected to compute the vascular density. White blood cells (WBC) count, PT, INR, PTT and D-dimer of both groups, and the infection duration of post-COVID patients were collected from clinical records and blood tests performed before the lung perfusion scintigraphy. Result(s): At the per lung analysis, post-COVID patients with persistent dyspnea showed reduced LTR (24.67>5.08) and higher MTR (52.51>5.22) compared to non-COVID patients (29.85>5.05 and 46.66>3.94, respectively;p<0.0001 for both), while UTR resulted bilaterally superimposable between the two groups. At CT imaging, the rates of emphysematous, infiltrated and collapsed volumes and the vascular density were bilaterally similar in both groups. In post-COVID patients, LTR correlated with the percentage of emphysematous (r=0.498;p<0.01), infiltrated (r=-0.464;p=<0.01) and collapsed (r=-0.463;p<0.01) lungs, while no significant correlations were observed between LTR and CTderived volumes in non-COVID subjects. There was no correlation between lung perfusion scintigraphy parameters with infection duration in post-COVID, WBC, and coagulation biomarkers in both groups. Conclusion(s): Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in post-COVID patients with persistent dyspnea without pulmonary embolism. This phenomenon is correlated with structural lung modifications, including lung parenchymal emphysema, infiltration and collapse, and is independent of infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, pulmonary non-thrombotic microvascular and endothelial dysfunction may be involved.

Persistent dyspnea in post-covid patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

Background-Aim: While there's a wide literature on CT abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy have been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism, presenting persistent dyspnea (POST-COVID). We compared perfusion scintigraphy and CT findings of these patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (NON-COVID). In POST-COVID patients, the correlation between lung perfusion scintigraphic findings and (1) CT abnormalities, and (2) clinical/ biochemical parameters were also assessed. Methods: 24 POST-COVID and 33 NON-COVID patients who underwent lung perfusion scintigraphy for dyspnea from March 2020 to December 2021 were retrospectively enrolled. High-resolution chest CT performed 15 days before/after lung perfusion scintigraphy were available in 15/24 POST-COVID and 15/33 NON-COVID patients. From scintigraphic images counting rates for upper, middle, and lower fields were calculated in order to compute their ratio with total lung counts (UTR, MTR, and LTR, respectively) for both right and left lungs (RL and LL, respectively). CT images were analyzed using a semi-automated segmentation algorithm of 3D Slicer ( http://www.slicer.org), obtaining total, infiltrated and blood vessels' volumes, in order to calculate the infiltration rate (IR) and vascular density (VD). White blood cells, platelets, PT, INR, PTT, fibrinogen, and D-dimer of 15/24 POST-COVID patients were also collected from blood tests performed before the lung perfusion scintigraphy. Results: POST-COVID patients with persistent dyspnea showed reduced LTR (RL 22.4% ± 6.6%;LL 24.7% ± 3.1%) and higher MTR (RL 55.2% ± 5.2%;LL 49.1% ± 3.3%) compared to non- COVID patients (RL-LTR 29.6% ± 6.0%, p<0.0001;LL-LTR 28.3% ± 4.6%, p = 0.001;RL-MTR 47.3% ± 4.2%, p<0.0001;LL-MTR 47.3% ± 3.0%, p = 0.036), while UTR resulted bilaterally superimposable between the two groups. Similar IR and VD values at CT imaging were documented bilaterally in both groups. In POSTCOVID patients, no significant correlations between lung perfusion scintigraphy and CT findings were observed. Correlation analysis indicated D-dimer levels as associated with UTR (Pearson's r = 0.664;p = 0.007) and MTR (Pearson's r = - 0.555;p = 0.032), while no parameter significantly associated with LTR was observed. Conclusions: Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in POST-COVID patients with persistent dyspnea in the absence of pulmonary embolism, independently from CT abnormalities, infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, lung nonthrombotic microvascular and endothelial dysfunction may be involved.

Metabolic correlates of olfactory dysfunction in covid-19 and Parkinson's disease (PD)

Background-Aim: A potential link has been investigated between hyposmia after COVID-19 and an increased risk to develop neurological long-term sequelae also in patients who experienced mild or moderate disease. Hyposmia is a common feature PD and parkinsonism has been reported after COVID-19 suggesting a potential link between SARS-CoV2 infection and PD. [18F]FDG PET may represent a suitable tool to capture potential common metabolic signature of hyposmia after COVID-19 and in PD patients. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naive PD patients. Methods: Forty-four patients who experienced hyposmia after SARSCOV2 infection underwent brain [18F]FDG-PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item ''Sniffin-Sticks'' test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [18F]FDG-PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple-regression- analysis was used to identify correlations between olfactory test-scores and brain metabolism in patients' subgroups. Results: COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p<0.002) and in middle and superior temporal gyri, medial/middle frontal gyri and right insula with respect to PD-hyposmia (p<0.012). With respect to COVIDhyposmia, PD-hyposmia patients showed hypometabolism in inferior/ middle occipital gyri and cuneus bilaterally. Olfactory test-scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in right middle temporal and anterior-cingulate gyri in COVID-hyposmia patients (p<0.006) and with bilateral cuneus/precuneus and left lateral occipital-cortex in PD-hyposmia patients (p<0.004). Conclusions: Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD. An impairment in olfactory judgement seem to underlie hyposmia in PD patients while a more restricted perception deficit seems to explain hyposmia in COVID-19. The potential long term neurological sequelae of COVID-19 are of interest from the clinical and economical point of view. Studies targeting symptoms common to COVID-19 and chronic neurological diseases and aiming to explore potential common pathways are of interest also to avoid unjustified claims about a future high incidence of neurodegenerative diseases secondary to the SARS-CoV-2 pandemic.

Survey of students regarding Zika infection: is the next generation aware of the dangers?

In 2016 and 2017 an outbreak of the Zika virus in new locales shocked populations into awareness of the disease and of its imputed ability to cause serious fetal abnormalities, particularly microcephaly. There was a major reduction in travel by people of child-bearing age. But the temporary regression in the spread, and preoccupation with COVID-19, seem to have overshadowed concern about Zika virus. In order to investigate this phenomenon, we conducted an online survey of 157 high-school students from four schools in different parts of the United States regarding their knowledge, practices, and attitudes about Zika virus. The mean age of the respondents was 16.4 +or- 1.1 years, 55% were girls, and 60% attended public (rather than private) schools. Most students (70%) had taken no steps to prevent Zika, but said they would tell their parents or a physician if they were exposed. They relied primarily on school and the internet (76% and 72%, respectively) as trusted sources of information about the virus. The majority (73%) said they would spend some time to learn more about Zika;girls exhibited more concern than did boys. Half (50%) of respondents knew the signs and symptoms of Zika, but only 20% knew all the ways Zika could be transmitted and 31% why Zika prevention was crucial for pregnant women and their partners. The results of this study suggest that comprehensive national preventive healthcare educational programs are needed.

Brain metabolism and persistent olfactory deficits after SARS-CoV-2 infection: An FDG-PET study

Background and aims: Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been associated with a number of neurological complications, including persistent hyposmia. Despite its relative frequency the neural bases of hyposmia post-SARS-Cov2 infection are to date poorly understood. Methods: 22 patients (12 males and 10 females;mean age 64±10.5 years, range 35-79) underwent whole-body [18] F-FDG-PET including a dedicated brain acquisition following their recovery after SARS-CoV-2 infection. Patients that previously required mechanic ventilation or showed severe respiratory distress syndrome due to SARSCoV- 2 infection were excluded given the potential independent effect of these clinical scenarios on brain metabolism. Among the enrolled patients, presence of isolated persistent hyposmia, as assessed with the smell diskettes olfaction test, was shown in fourteen subjects. A voxelwise analysis was used to identify brain regions of relative hypomebolism in hyposmic patients compared to a group of 61 age- and sex-matched healthy controlsStructural connectivity of these regions was assessed with the BCB toolkit. Results: Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in hyposmic patients with respect to controls. Structural connectivity maps showed the involvement of the bilateral longitudinal fasciculi. Conclusion: Here we provide the first evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-CoV-2 infection without an history of severe respiratory distress. [18]F-FDG-PET may play a role in the identification of long-term brain functional sequelae of COVID-19.