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.

GENERATIVITY AND OLDER ADULTS' COVID-19 ADJUSTMENT AND MENTAL HEALTH

Generativity, the capacity to be productive, caring, and concerned with the well-being of the next generation, has been linked to positive mental health outcomes and posttraumatic growth (Bellizzi, 2004). Generativity may be particularly important nowadays as older adults adjust to the pandemic and its aftermath. For example, after months of social distancing, the availability of vaccines has enabled many older adults to begin resuming social activities. Considering the meaning-making function of generativity, generativity may be associated with more positive outcomes, including better mental health and views on quality of life and family relationships during this post-pandemic adjustment period. The current study used a community sample of 136 older adults (M age = 67.77, range 50-91;69.3% females;93% White) to explore whether generativity predicted older adults' anxiety and depressive symptoms, and attitudes about how the pandemic affected their quality of life and family relationships. Using hierarchical linear regressions controlling for age and gender, we found that generativity was negatively linked to anxiety and depressive symptoms. Furthermore, those with greater generativity were more likely to report that their family relationships improved because of the pandemic. In contrast, generativity was not associated with positive growth in the personal domain or with perceptions that the pandemic had harmed either personal or family domains. Our findings are consistent with Erikson's theory on the important role that generativity plays in shaping well-being and psychological health in older adults, and our findings suggest these effects may be especially pronounced during this post-pandemic adjustment period.

THE ROLE OF SOCIABILITY IN OLDER ADULTS' ADAPTATION TO COVID-19

Some older adults may be particularly sensitive to the negative effects of social disruptions due to COVID-19 (Tyrrell & Williams, 2020). For example, the unique circumstances of the pandemic may have made greater sociability a liability (Wijngaards et al., 2020). The current study used a community sample of 136 older adults (M age = 67.77, range 50-91;69.3% females;93% White) to explore whether sociability moderated links between disruptions to contact with friends and family and indicators of mental health. Using a series of hierarchical linear regressions, we found that sociability moderated the association between disruptions in family interactions and depressive symptoms. For more sociable individuals, disruptions in family interactions were more strongly positively associated with depressive symptoms. Given the potential for future social disruptions due to COVID-19, our findings point to the importance of considering the role of sociability in developing interventions targeting older adults.

A six-month unsupervised training program does not improve ankle joint mobility in soccer players

Problem Statement: Soccer practice can induce marked changes in ankle joint mobility (AJM) with dreaded consequences related to the quality of balance, posture and gait. Moreover, a limited ankle range of motion may represent an important risk factor for injuries and negatively affect performance. Purpose: The aim of this study was to evaluate the effects of a stretching training protocol (STP) on the AJM of adult male soccer players (SP). Material and Methods: 34 amateur male SP (age 29.0±4.6 years) and 24 non-soccer players (control group) matched for age, gender and BMI were included in this study. In both groups AJM and muscle strength were evaluated by inclinometer and Jamar hydraulic hand dynamometer respectively. Moreover, data on sports practiced, years of activity, history of injuries, dominant kicking leg, and presence of athletic trainers were collected. SP group performed six months of a STP that included 4 exercises aimed at improving AJM. Due to the Covid-19 pandemic the STP was suspended for 4 weeks in the middle period of the study. Results: At baseline, SP group showed reduced AJM compared to controls (116.1±13.1° vs. 137.7±13.6;p<0.001) while muscle strength was similar (45.0±7.5 vs 48.0±8.9 kg). STP produced a non-significant effect on AJM (116.1±13.1 vs 116.8±15.1°). No differences were found between the two groups considered as regards the difference in mobility between the two ankles (right vs left;dominant vs non-dominant). Considering the initial values, there was a direct correlation between HS and BMI (r=0.38;p<0.025), while AJM showed an inverse correlation with years of activity (-0.36;p<0.037). No correlation was found between hand grip test and AJM. Conclusions: SP showed a significant reduction in AJM which was difficult to recover even following a STP. The interruptions of sport activity due to the Covid-19 pandemic and the absence of athletic trainers in the sports clubs involved, in addition to the long history of soccer practice could justify, at least in part, the results obtained. © JPES.

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.

Keeping breast cancer survivors exercising with the “movement and health beyond care” (MOVIS) clinical trial in the age of COVID-19: Amelioration of heart rate variability and cardiorespiratory fitness

Background: MoviS: 'Movement and health beyond care' is an ongoing randomized controlled trial aiming to educate breast cancer (BC) survivors on the benefits of exercise and proper nutrition habits. Methods: The study included thirty women (17.4% of the total planned cohort of 172 patients) with stage 0-III non-metastatic BC (age: 53.5±7.6 yrs;BMI: 25.3±4.9 kg/ m2) randomly allocated to the Intervention Arm (IA;supervised exercise training: “MoviS Training”) or control arm. The MoviS Training consists of 12 weeks of aerobic exercise (2 d/week of supervised and 1 d/week of unsupervised exercise) which intensity and duration gradually increased from 40 to 70% of heart rate reserve and from 20 to 60min, respectively. Both arms received nutritional and lifestyle counselling based on WCRF 2018 guidelines through the DIANA-Web platform and motivational interviewing. As the planned protocol was changed due to nationwide lockdown to contain the spread of COVID-19, IA performed home-based exercise sessions, which were remotely supervised using heart rate monitors. Heart rate variability (HRV;by 24-Holter monitoring), cardiac function indexes (by echocardiography with speckle tracking imaging), and cardiorespiratory fitness (by estimated maximal oxygen uptake [VO2max]) were evaluated at baseline and after the intervention period. Results: There were no adverse events during training. Baseline evaluation revealed no systolic disfunction (mean LVEF 60.4±4.5%) and a mild reduction (values 3 -18%) in global longitudinal strain in 26% of patients. HRV improved in both time and frequency domains: ASDNN/5min (50.6±14.4 to 55.2±16.7 msec, p=0.033);very low frequency (VLF) (1597±967 to 1881±963 msec, p=0.04);low frequency (LF) (613±404 to 731±542 msec, p=0.004);total power (2627±1393 to 3034±1669 msec, p=0.034). HRV parameters tended to improve to a greater extent in IA group (Coefficient of Variation: ASDNN/5min 13.7% vs 4.6%, LF 27% vs 10%, total power 26.5% vs 5.1%). Cardiorespiratory fitness level increased significantly in both groups (VO2max from 30.7±5.7 to 33.9±6.6mL/kg/min, p<0.001). Conclusion: During COVID-19 lockdown, short-term remotely supervised exercise training and recommendations on a healthy lifestyle lead to a significant improvement in HRV parameters and cardiorespiratory fitness in BC survivors.

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.

Health-related quality of life, heart rate variability and physical fitness in breast cancer patients during the COVID-19 lockdown: The impact of a lifestyle program ('MoviS Project, movement and health beyond the care' (CESU approval n. 21/10.07.2019)

Background: Breast cancer (BC) is the most common invasive cancer in women and evidence has shown that exercise can significantly improve the outcomes of BC survivors. MoviS: 'Movement and Health Beyond Care' is a randomized controlled trial, which aims to educate cancer patients after adjuvant therapy on the benefits of exercise and proper nutritional plan. Material (patients) and methods: Thirty women with stage 0-III non-metastatic BC recruited 12-month postsurgery (age: 53.5±7.6;BMI: 25.3±4.9) were randomized in two groups: intervention arm received 3-month aerobic training (40-70% of the heart rate reserve;20 to 60 min 3-day/week);control arm with usual care recommendations. Patients enrolled in January 2020 were monitored for diet habits by DianaWeb platform, they carried out the exercise training across the COVID-19 pandemic shifting from the gym to a home-based exercise program. The objective was to investigate the effects of lifestyle program on quality of life by EORTC QLQ-C30 and health-related QoL parameters such as cardiac function indexes;heart rate variability (HRV) (by repeated Holter 24h) and cardiorespiratory fitness by estimated maximal oxygen uptake (VO2max). Results: There were no adverse events and a high attendance was registered considering the challenges to be overcome in shifting to a home-based exercise program. Statistical analysis revealed a significant improvement in both arms in QLQ scale score: in global health status (from 64.7±17 to 15.9±13;coefficient of variation (CV) 15.9%;p=0.0015);physical functioning (from 54.4±12.3 to 6±6.6;CV 13.9%;p=0.0005);fatigue (from 26.3±23.4 to 11.9±14.3;CV -54.9%;p=0.0008) and showed a general improvement over time even on the social functioning (from 47.2 ± 22.8 to 66.7±00;CV 41.2%;p=0.0001). Both groups had a significant improvement in HRV parameters in both time and frequency domain: average SDNN/5min and VLF increased (from 50.6±14.4 to 55.2±16.7msec, p=0.033 and form 1597±967 to 1881±963 msec, p=0.04, respectively);mean heart rate decreased (from 76.6 ±7.8 to 73.7±8.3 bpm after training, p=0.009) and both arms improved the cardiorespiratory fitness level (VO2max from 30.7±5.7 to 33.9±6.64 mL/kg/min;CV 10.3%;p<0.001). Conclusions: Despite the challenges faced during the pandemic, a change in lifestyle integrating exercises, nutrition and educational counseling provides benefit to BC patients when delivered in a clinic-based setting group including the exercise specialists.

Beneficial effects of exercise in oncology - MoviS: ‘Movement and Health Beyond Care’

Background: MoviS: ‘Movement and Health Beyond Care’ is a 3-year randomized controlled trial aiming to educate cancer patients after adjuvant therapy on the benefits of personalized physical activity (PA) and a proper nutritional plan. Methods: In this project, breast cancer (BC) patients who consent to participate will be randomized to Interventional Arm (A), consisting of 3-months of Movis Training, or Control Arm (B), consisting of standard care with no supervised PA. The Movis Training consists of 3-months of aerobic training (2 d/week of supervised training and 1 d/week of unsupervised exercise) with an increase in exercise intensity (40-70% Heart Rate Reserve) and duration (20-60 min). Ad interim analyses every 3-months up to 1-year will be included. The first cohort of eligible BC survivors were enrolled in January 2020 and carried out the Movis Training even during the COVID-19 pandemic. The primary outcome is improvement of Quality of Life (QoL) assessed by European Organization for Research and Treatment of Cancer QoL (EORTC QLQ-C30). The secondary outcomes are improvement of health-related QoL parameters such as: PA level (International Physical Activity Questionnaire;SenseWear Armband), fitness (VO2max), flexibility, strength, psychological well-being (Psychological distress Inventory;Profile of Mood States and diet habit (DianaWeb, MEDIET modified and recall 24h);Anthropometric measurement, Body mass (kg);BMI (kg/m2);body composition. Results: The expected improvement (mean ± SD) of the QoL in Arm A at 3-months is 15.1 ± 17.7, while in Arm B is 6.1 ± 17.1 (Cohen d effect size=0.51, medium effect). Using a t test for independent samples, with 0.05 alpha and 0.80 1-beta will require 60 subjects per group. Considering an expected drop-out of 30%, a total of 172 patients will be recruited. Conclusions: The targeted exercise oncology through multidisciplinary team would like to provide a coordinated program of cancer care to improve health care quality, improve prognosis, increase survival times and QoL and reduce the risk of BC recurrence. Legal entity responsible for the study: Elena Barbieri. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.