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The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2-ERIC-PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.
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Brain Ischemia , COVID-19 , Ischemic Preconditioning, Myocardial , Stroke , Animals , Education , Ischemia , Treatment OutcomeABSTRACT
Introduction: COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often presents with a spectrum of symptoms at varying levels of severity, ranging from asymptomatic patients to those with fatal complications, such as myocarditis. With increased availability of COVID-19 vaccines, the awareness of possible side effects has expanded as reports surface. This study reviewed cases of myocarditis following COVID-19 vaccination and with existing literature on COVID-19 infection-induced myocarditis to compare clinical courses and analyze possible mechanisms of action. Methods: A systematic review of literature was conducted to identify published case reports (as of February 3, 2022) pertaining to the development of myocarditis following COVID-19 vaccination with either Pfizer or Moderna for an in-depth analysis. Additional subgroup analyses were conducted based on age, past medical history, vaccine manufacturer, and dose number. Results: There were 53 eligible case reports that were included in this study. Patients were mostly male with a median age of 24 years, and the most reported symptom upon presentation was chest pain. Seventy percent of the cases involved the Pfizer vaccine with a majority of myocarditis developing subsequent to second dose. Resolution of symptoms was achieved in all but one patient. Clinical severity, as measured primarily by left ventricular ejection fraction, appeared to be worse among adult patients than pediatric, as well as for patients with comorbidities. Conclusion: This study revealed an observable association between COVID-19 vaccines and myocarditis. However, the clinical course and prognosis seem favorable and less prevalent than those conferred from natural infection.
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Background. Anti-SARS-CoV-2 monoclonal antibodies afford prompt immunity, have demonstrated reduction in severe COVID-19 in high risk ambulatory patients, and are available through Emergency Use Authorization. Challenges exist, however, to widespread utilization. Methods. This operations study 11/23/20-4/30/21 identified patients meeting monoclonal AB EUA criteria by test results or referral. Outreach to harder-hit neighborhoods included connecting with primary care teams and testing sites. Infusion centers with staff trained in infection control, rapid response and drug preparation were utilized. The primary study outcome was treatment of qualifying patients. Secondary outcomes included infusion complications, hospitalization/ death, and symptom resolution. Investigational review board approval was obtained. Results. 367 patients were treated: mean age of 63, 201(55%) male, 276(75%) white, 54(15%) black. All patients had a first positive direct SARS-CoV-2 test within 10 days, 232(63%) had > 1 high-risk qualification, 32(9%) were vaccinated for SARSCoV-2. Of patients with available zipcodes, 135(38%) had a Community Need Index >3.5 and 157(45%) a Social Vulnerability Index >0.5. 190(52%) received bamlanivimab, 93(25%) casirivimab/imdevimab, 84(23%) bamlanivimab/etesevimab. Four patients experienced infusion reaction, 1 with anaphylaxis. 172(73%) of 236 patients were symptom free at day 5. 20 patients (5%) were hospitalized for COVID-19 within 30 days with a median time from symptom onset to infusion of 7 days, 11(55%) were admitted within 24 hours, 1 died. Conclusion. Our study demonstrates that treatment with anti-SARS-CoV-2 monoclonal antibodies is feasible in a high resource setting. There were no related SARS-CoV-2 exposures and therapy was well tolerated. Trials of anti-SARS-CoV-2 monoclonal antibodies have reported lower rates of hospitalizations in treated patients than we found. This may reflect the expanded time frame for EUA therapy as compared to clinical trials, differences in real world patients or viral variants. Given potential benefit in unvaccinated patients or those at risk for poor vaccine response, the equitable utilization of anti-SARS-CoV-2 monoclonal antibody therapy in early COVID-19 should remain a focus for researchers and clinicians.
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Background. The National Institutes of Health Office of AIDS Research recommend that patients with HIV be prioritized for COVID-19 vaccination due to high rates of co-morbidities and sociodemographic risk factors that place them at increased risk for severe disease. However, COVID-19 vaccines were not distributed specifically to those in high-risk medical categories in Nebraska, and HIV clinics were not included in the state's COVID-19 vaccine delivery system. As a result, barriers to vaccine uptake emerged and interventions to mitigate them were needed. Methods. A multi-faceted and iterative program aimed at improving COVID-19 vaccine uptake was implemented at the University of Nebraska Medical Center's (UNMC) HIV clinic in Omaha, Nebraska in January 2021. A multidisciplinary task force was established in late January 2021 and met on a weekly basis to provide staff and patient education, linkage to vaccines, and review and analysis of vaccine completion rates as shown in the figure. Outreach interventions were continuously revised based on patient and staff feedback as well as updated data and vaccine availability. Results. All 1188 patients of the UNMC HIV clinic were ultimately eligible for the COVID-19 vaccine, but availability was on a rolling basis by age group, profession, county, and, ultimately, co-morbidities. 76% were male, 45.8% non-white, median age 48, and 73% had income less than 400% of federal poverty level. Of the 1188 eligible patients, 63.1% (n=751) had received at least one dose the COVID-19 vaccine and 59.3% (n=705) had completed the COVID-19 vaccine series by June 4, 2021. In comparison, 49.32% of the population of the state of Nebraska had initiated the COVID-19 vaccine series and 43.12% had completed the vaccine series by that date. Among our clinic patients, 27.9% (n=261) of those who had received at least one vaccine were assisted by our task force. 4.5% were noted to have a potential barrier at the time of outreach and these included hesitancy (3.5%), language (1.2%) and transportation (0.9%). Conclusion. A multi-faceted and iterative program to improve COVID-19 vaccine uptake in a high-risk patient population resulted in high rates of vaccine completion.
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Background: Recent reports have revealed that coronavirus disease 2019 (COVID-19) is associated with liver injury The burden of liver injury in liver transplant (LT) recipients remains unknown We conducted a multi-center study to evaluate the prevalence, pattern and predictors of liver injury in LT recipients with COVID-19 and its impact on clinical outcomes Methods: The was carried out by the consortium of investigators to study COVID-19 in chronic liver disease (COLD) (registered Clinicaltrials gov NCT04439084) Inclusion criteria constituted: age > 18 years, laboratory confirmed diagnosis of COVID-19 and history of LT. We collected de-identified data on patients diagnosed before May 30, 2020 For the analysis on liver injury, only patients who had laboratory values for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) prior to- and during COVID-19 infection were included The primary outcome was the presence of acute liver injury The secondary outcome was all-cause mortality within 90 days of diagnosis Logistic regression analyses were used to determine interdependent risk factors of primary outcome Results: We included 112 adult LT recipients from 21 US medical centers with confirmed diagnosis of COVID-19 The median age of the cohort was 61 years (IQR 20), and 54 5% (n = 61) were male There were 39 3% (n = 44) Hispanic, 27 7% (n = 31) non-Hispanic white, and 25 9% (n = 29) non-Hispanic African-American The all-cause mortality was 22 3% (n = 25);72 3% (n = 81) were hospitalized and 26 8% (n = 30) were admitted to the intensive care unit (ICU) 81 patients had data for analysis of liver injury 34 6% of LT patients had liver injury, Mild to moderate liver injury (ALT 2-5x ULN) in 22 2% (n=18) and severe (ALT > 5x ULN) in 12.3% (n = 10). Younger age (p = 0 009, odds ratio (OR) 2 06 [1 20-3 54]), Hispanic ethnicity (p = 0 011;OR 6 01[1 51-23 9]), metabolic syndrome (p = 0 016;OR 5 87 [1 38-24 99]), receipt of vasopressors (p = 0 018;OR 7 34 [1 39-38 52]) and antibiotic use (p = 0 046;PR 6 93 [1 04-46 26]) were associated with independent risk of liver injury on multivariate logistic regression Immunosuppression was modified in approximately half the patients (49.4%, [n = 40]) Reduction in immunosuppression during COVID-19 was not associated with liver injury (p = 0 156) or risk for mortality (p = 0.084). Presence of liver injury was significantly and independently associated with higher overall mortality (p = 0 007;OR = 6 91 [95% CI: 1 68-28 48]) in LT recipients Conclusion: Mild to moderate liver injury was common in LT patients diagnosed with COVID-19 Immunosuppression was modified during COVID-19 in half the patients but was not associated with liver injury or mortality Younger age, Hispanic ethnicity, metabolic syndrome, vasopressor and antibiotic use were associated with independent risk of liver injury Lastly, liver injury was associated with higher mortality rate in LT recipients with COVID-19.
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Establishing the impact of the coronavirus disease 2019 (COVID-19) pandemic on utilisation of mental health services is a potentially useful means of measuring the psychiatric consequences of the COVID-19 pandemic and related lockdown. Here, the authors describe their study, which compared the use of an early intervention in psychosis service in the four weeks immediately prior to the COVID-19 regulated lockdown in the UK, with the four weeks immediately subsequent to lockdown.