Citations

Abstract Background Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) receptor as a means to enter the host. High density of ACE2 receptor in vascular endothelial cells may explain why vascular complications related to endothelial dysfunction occur in COVID-19. However, in vivo assessment of vascular endothelial function during COVID-19 has not been reported. Objective To investigate the vascular endothelial function and its temporal changes in COVID-19 patients. Methods In this prospective blinded study, systemic endothelial function was assessed using plethysmography-derived peripheral arterial tonometry (PAT). The reactive hyperemia index (LnRHI), a measure of endothelium-mediated hyperaemia, and the augmentation index, a measure of arterial vascular stiffness, were measured in 102 individuals across three study groups using PAT: group 1 (active infection), constituted by 20 patients hospitalised due to acute COVID-19; group 2 (past infection), constituted by 52 patients who had recovered from COVID-19; and group 3 (controls), constituted by 30 healthcare workers not infected by SARS-CoV-2. Additionally, among group 1, PAT assessment was repeated in 14 patients several weeks after recovery from acute COVID-19. PAT studies were analysed at a blinded fashion with respect to the assigned study group. Results Lower resting PAT amplitude was found in acute COVID-19 patients compared to the other groups (ratio of arterial tone signal between hyperemia to resting condition was 1.5 [interquartile range, 1.1] in group 1, 1.3 [0.3] in group 2 and 1.2 [0.3] in group 3, p=0.041). On the contrary, no significant differences between groups were found with respect to the hyperemic PAT amplitude (867.9 [486.1] in group 1, 944.7 [748.1] in group 2 and 819.3 [639.6] in group 3, p=0.444). Due to the lower resting PAT amplitude, there was a paradoxically significantly increased LnRHI during acute COVID-19 compared to past infection and controls (0.73 [0.32] vs. 0.53 [0.31] vs. 0.44 [0.23], respectively; p=0.013) (Figure A). Furthermore, among group 1 patients, LnRHI normalised markedly from acute COVID-19 to past infection stage (0.73 [0.32] vs. 0.49 [0.28], respectively; p=0.005) (Figure B). Augmentation index was significantly higher during acute COVID-19 compared to past COVID-19 and controls (9.6 [19.1] in group 1, 6.97 [18.6] in group 2 and −0.35 [20.53] in group 3; p=0.045 for COVID groups vs. controls). Conclusions Non-invasive assessment of systemic vascular endothelial function with PAT revealed significant differences between subjects with acute COVID-19, past COVID-19 and controls. Lower baseline PAT amplitude and high augmentation index suggest vasoconstriction at rest during the acute phase of COVID-19. These findings open new research opportunities to investigate the prognostic value of PAT in COVID-19 patients. Funding Acknowledgement Type of funding sources: None.

Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

During the COVID-19 pandemic, efforts have been made worldwide to develop effective therapies to address the devastating immune-mediated effects of SARS-CoV-2. With the exception of monoclonal antibody-mediated therapeutics and preventive approaches such as mass immunization, most experimental or repurposed drugs have failed in large randomized clinical trials ( https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline ). The worldwide spread of SARS-CoV-2 virus revealed specific susceptibilities to the virus among the elderly and individuals with age-related syndromes. These populations were more likely to experience a hyperimmune response characterized by a treatment-resistant acute lung pathology accompanied by multiple organ failure. These observations underscore the interplay between the virus, the biology of aging, and outcomes observed in the most severe cases of SARS-CoV-2 infection. The ectoenzyme CD38 has been implicated in the process of “inflammaging” in aged tissues. In a current publication, Horenstein et al. present evidence to support the hypothesis that CD38 plays a central role in altered immunometabolism resulting from COVID-19 infection. The authors discuss a critical but underappreciated trifecta of CD38-mediated NAD + metabolism, aging, and COVID-19 immune response and speculate that the CD38/NAD + axis is a promising therapeutic target for this disease.

AbstractBackgroundThe SARS‐CoV‐2 pandemic disrupted hospital operations, affected the blood supply, and challenged the health care system to develop new therapeutic options, including convalescent plasma (CCP). The aim of this study is to describe and analyze blood supply fluctuations and the use of convalescent plasma in 2020.MethodsAABB distributed a weekly and biweekly questionnaire through email to hospital‐based members (HBM).ResultsThe survey was sent to 887 HBM with 479 unique respondents, most of the hospitals served pediatric and adult patients, and all states of the country participated, except Idaho and Vermont. Fifty four percent of HBM reported increased wastage in the early phase of the pandemic (May), which decreased to 4% by the end of June and throughout the rest of the year. The majority of HBM reported receiving alerts from their blood suppliers reporting blood shortages throughout the year. During March and April, only 12% of HBM were performing elective surgical procedures. The top reasons to delay procedures were: bed availability (28%); COVID‐19 caseload (23%; and blood availability (19%). By mid‐April, 42% HBM had transfused CCP and reported >24 h delay in getting the units; the vast majority obtained CCP using the Expanded Access Protocol, and later, the Emergency Use Authorization. HBM consistently prioritized the most severe patients to receive CCP, but the proportion of severely ill recipients fell from 52% to 37% between May and October, with an increase from 5% to 21% of HBM providing CCP transfusion early in the course of the disease.DiscussionBlood utilization and availability fluctuated during the pandemic. The fluctuations appeared to be related to the number of COVID‐19 in the community. The use and regulatory landscape of CCP rapidly evolved over the first 8 months of the pandemic.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Background: Combined therapy with levothyroxine (LT4)/L-triiodothyronine (LT3) has garnered attention among clinicians and patients as a potential treatment alternative to LT4 monotherapy. The objective of this study was to compare the benefits and harms of LT4/LT3 combined therapy and LT4 monotherapy for patients with hypothyroidism. Methods: A systematic search in MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials was performed by a librarian from inception date until September 2020. Randomized clinical trials and quasiexperimental studies comparing combined therapy (LT4/LT3) versus monotherapy (LT4) for adult patients with hypothyroidism were considered for inclusion. Independent data extraction was performed by paired reviewers. A meta-analysis comparing standardized mean differences of the effect of each therapy was performed on clinical outcomes and patient preferences. Proportions of adverse events and reactions were assessed narratively. Results: A total of 1398 references were retrieved, from which 18 fulfilled the inclusion criteria. Results supported by evidence at low-to-moderate certainty evidence did not display a difference in treatment effect between therapies on clinical status, quality of life, psychological distress, depressive symptoms, and fatigue; all measured with standardized questionnaires. Furthermore, meta-analysis of patient preferences revealed higher proportions of choice for combined therapy (43%) when compared with monotherapy (23%) or having no preference (30%). When evaluating treatment adverse events or adverse reactions, similar proportions were observed between treatment groups; meta-analysis was not possible. Conclusions: The available evidence at low-to-moderate certainty demonstrates that there is no difference in clinical outcomes between LT4/LT3 combined therapy and LT4 monotherapy for treating hypothyroidism in adults, except for a higher proportion of patient preferring combined therapy. Adverse events and reactions appear to be similar across both groups, however, this observation is only narrative. These results could inform shared decision-making conversations between patients with hypothyroidism and their clinicians. PROSPERO Registration ID: CRD42020202658.