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The neurological complications of COVID-19 are an expansive and heterogeneous topic. This chapter discusses the neuropathophysiology of COVID-19 and the potential mechanisms through which the disease leads to neurological manifestations while also exploring historical viruses that have also led to neurological sequelae. These complications are then characterized and classified into several groups with support from contemporaneous evidence. In addition to this we examine common neurological imaging and their findings and finally discuss the greatest needs moving forward with regard to evidence and research through collaborative efforts. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
ABSTRACT
Acute severe symptoms and long-term sequelae caused by the novel coronavirus disease (COVID-19) are still major concerns for public health. In particular, it is an emerging need to prevent the overburn of health workers as well as the collapse of health care systems. To reach this purpose, it should be necessary to evaluate a standardized pre-hospital management for COVID-19 patients, but data about it are lacking. Thus, the aim of the present chapter is to analyze the in-hospital gesture hypothesizing its reproducibility at bedside.Meta-analyses and randomized clinical trials assessed were focused on the following topics: (1) early diagnosis through viral demonstration and serological testing;(2) home setting evaluation;(3) standardized multidimensional assessment of COVID-19 patients, including an early identification of specific clinical symptoms as well as a prognostic stratification through laboratory biomarkers and portable imaging techniques;(4) safe and easily administrable drugs, considering both new medications and repurposed molecules;(5) protocols regarding bedside oxygen therapy, prone positioning, and pulmonary rehabilitation.To date, several procedures for the in-hospital management of COVID-19 patients could be easily and safely applied in the outpatients' care. The institution of dedicated international open-access data banks could be useful to realize standardized pre-hospital protocols, and the implementation of remote approaches could provide the possibility to guarantee a continuous follow-up for these patients. Global efforts focused on this goal could represent the only way to decrease the pressure on health care systems and to restore their essential function, still allowing an effective management of mild-to-moderate COVID-19 stages. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Growing data are confirming the association between the novel coronavirus disease (COVID-19) and eye disorders, including ocular alterations and neuro-ophthalmic manifestations. The main pathophysiological mechanisms considered included a direct infection through the ocular surface, a post-viremia secretion of the virus from the lacrimal glands, and a viral dissemination through the bloodstream. According to the different ways of contagion, different structures could be involved.The most common ocular symptoms reported in COVID-19 patients were dry eye, redness, tearing, itching and pain. Among symptomatic patients, most of them presented conjunctivitis. Considering the posterior chamber, retinal artery and vein occlusions were described in few clinical reports;moreover, some studies presented cases of paracentral acute middle maculopathy occurring in COVID-19 patients. The involvement of the choroid seems to be rare, and a single case of atypical choroiditis was currently described. Between neuro-ophthalmic manifestations, optic neuritis appear to be relatively frequent and generally not associated with magnetic resonance imaging abnormalities. Some reports showed the involvement of the ocular motor nerves, often presenting with palsy. Miller Fisher syndrome has been showed in rare cases;however, this association could be corroborated by the several reports describing Guillain-Barré syndrome occurrence in COVID-19 patients.In line with well-known previous viral infection, COVID-19 seems to be associated with eye involvement. Thus, ocular and neuro-ophthalmic symptoms and signs should be carefully assessed and monitored in these patients. To reach this purpose, it is critical to implement remote diagnostic techniques. Moreover, the comprehension of the pathogenetic mechanisms is still scarce and no standardized diagnostic protocol was established for these patients, making necessary further studies to improve current understandings. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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This final chapter of the book "Frontiers of COVID-19: Scientific and Clinical Perspectives of the Novel SARS-CoV-2" takes the contents of the book and lesson learned of the clinical and epidemiological aspects of COVID-19 to the next level and provides guidelines and the road map into the future, beyond COVID-19. The aim is to present the most recent understanding of the fast-changing dynamics of COVID-19 and to help our clinicians and physicians better prepare for the road ahead. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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This book aims to serve the critical interests of the global community by supplying the most current knowledge and understanding of Covid-19 epidemiology, treatment, and prognoses. There was much uncertain and contradictory information published in the first year of the novel coronavirus. The dynamics of COVID-19 have now been realized, including the type of antibodies produced in infected patients and their limited lasting endurance. This book will set the record straight on the concept of "herd immunity” and explore the current vaccine trials taking place in different countries. This comprehensive book will illuminate recent advances regarding COVID-19 and offer a possible roadmap on how to move forward. Frontiers of COVID-19: A Pathophysiology and Epidemiology Roadmap of Novel Coronavirus Disease will be a vital and forward-looking guide for infectious disease clinicians, scientists and researchers, and students at the graduate level. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
ABSTRACT
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.
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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.
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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.