Clinical outcomes and immune responses to SARS-CoV-2 vaccination in severe aplastic anaemia.

Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID-19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin (p = 0.52), platelet count (p = 0.67), absolute lymphocyte (p = 0.42) and neutrophil (p = 0.98) counts prior to and after completion of vaccination series. Relapse after vaccination, defined as a progressive decline in counts requiring treatment, occurred in three patients (6%). Humoural response was detectable in 90% (28/31) of cases by reduction in an in-vitro Angiotensin II Converting Enzyme (ACE2) binding and neutralization assay, even in patients receiving ciclosporin (10/11, 90.1%). Comparison of spike-specific T-cell responses in 27 SAA patients and 10 control subjects revealed qualitatively similar CD4+ Th1-dominant responses to vaccination. There was no difference in CD4+ (p = 0.77) or CD8+ (p = 0.74) T-cell responses between patients on or off ciclosporin therapy at the time of vaccination. Our data highlight appropriate humoural and cellular responses in SAA previously treated with IST and true relapse after vaccination is rare.

Site-level variability in the processes of care and outcomes over time among patients with COVID-19 and myocardial injury: Insights from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain. Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020-January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test. Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend<0.001), and reduction in mortality (p-trend<0.001), without significant change in ICU admissions (p-trend = 0.08). Similar variability and temporal trends were seen among patients with ≥5-fold cTn elevation. Conclusions: The use of invasive coronary angiography among patients with COVID-19 and myocardial injury was very low during the early pandemic. We found moderate institutional variability in processes of care with an uptrend in invasive catheterization and LVEF assessment, and downtrend in mortality. Comparative effectiveness studies are needed to examine whether variability in care is associated with differences in outcomes.

Safety and immunogenicity of COVID Influenza Combination Vaccine

Background. We developed a COVID-Influenza Combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) and quadrivalent influenza hemagglutinin (HA) protein nanoparticles (qNIV), and Matrix-MTM adjuvant. rS/Matrix-M previously demonstrated efficacy against COVID-19 in Phase 3 trials, while qNIV/ Matrix-M previously demonstrated induction of broadly cross-reactive antibodies. Here we report preliminary safety and immunogenicity results of a first-ever Phase 1/2 CIC dose-finding trial. Methods. Seropositive (COVID-19 vaccinated >= 8 weeks prior) participants (N=642) aged 50-70 years were randomized equally, to receive two intramuscular doses, 56 days apart, to 1 of 14 different dose/formulations of CIC using a design of experiments approach (dose range: rS 2.5-22.5ug, HA5-60ug;and 50ug Matrix-M), or to 1 of 2 reference formulations of either standalone rS with Matrix-M [2 doses] or qNIV with Matrix-M [1 dose only]. Pre- and post-vaccination (Days 0, 28, 56, 70, 84, 182) immunogenicity assessments including SARS-CoV-2 anti-S IgG and influenza HAI antibodies to vaccine-homologous strains. Reactogenicity was assessed 7 days following each dose, and safety outcomes assessed through Day 70. Multiple regression was used to create predictive models to assess antibody response surfaces and for dose optimization. Results. All CIC formulations were well tolerated, with a reactogenicity and safety profile generally comparable to standalone rS or qNIV. Regression modelling of post-first dose responses revealed that both rS and HA antigens in a CIC formulation modestly interfered with each other, however, interference was overcome with dose adjustment across a range of rS/HA doses. Specifically, higher rS dose ( >20ug), in a dose dependent fashion, overcame HA interference, closely matching standalone rS IgG reference responses (GMEU 16,818), whereas lower, intermediate HA dose overcame rS interference, closely matching standalone HA reference HAI responses for H3N2 (GMT 145), H1N1 (GMT 134), and B-Victoria (GMT 66);while modestly (at least 34%) lower than the reference B-Yamagata response (GMT 101). Conclusion. CIC formulations were well tolerated and immunogenic, with various dose combinations achieving response comparable to standalone vaccines.

Impact assessment of COVID-19 global pandemic on water, environment, and humans.

One of the most significant threats to global health since the Second World War is the COVID-19 pandemic. Due to COVID-19 widespread social, environmental, economic, and health concerns. Other unfavourable factors also emerged, including increased trash brought on by high consumption of packaged foods, takeout meals, packaging from online shopping, and the one-time use of plastic products. Due to labour shortages and residents staying at home during mandatory lockdowns, city municipal administrations' collection and recycling capacities have decreased, frequently damaging the environment (air, water, and soil) and ecological and human systems. The COVID-19 challenges are more pronounced in unofficial settlements of developing nations, particularly for developing nations of the world, as their fundamental necessities, such as air quality, water quality, trash collection, sanitation, and home security, are either non-existent or difficult to obtain. According to reports, during the pandemic's peak days (20 August 2021 (741 K cases), 8 million tonnes of plastic garbage were created globally, and 25 thousand tonnes of this waste found its way into the ocean. This thorough analysis attempts to assess the indirect effects of COVID-19 on the environment, human systems, and water quality that pose dangers to people and potential remedies. Strong national initiatives could facilitate international efforts to attain environmental sustainability goals. Significant policies should be formulated like good quality air, pollution reduction, waste management, better sanitation system, and personal hygiene. This review paper also elaborated that further investigations are needed to investigate the magnitude of impact and other related factors for enhancement of human understanding of ecosystem to manage the water, environment and human encounter problems during epidemics/pandemics in near future.

Indirect Effects of Covid-19 on Water Quality

The provision of safe water and functioning waste management play key roles in preventing and combatting disease outbreaks such as the Covid-19 pandemic. Good water quality is needed for effective hygiene measures like washing hands as well as for lowering pathogen transmission. Almost all over the world, especially in developing countries, water is vulnerable and at high risk and surging insecurity with time. Effective water management, sanitation, and hygiene help to protect lives during the global COVID-19 pandemic. While sanitation and hygiene also disturb the quality and increase water consumption per capita to 40% comparatively and wastewater production in many developing countries. This rapid increase in water consumption puts direct pressure on water reservoirs and inadequate management of wastewater is also a serious threat to waterways, nowadays. Similarly, the quality of water bodies is significantly affected by the COVID-19 pandemic, but the risk of transmission of COVID-19 through sewerage systems is recorded as low. Hence, the current review paper is planned to highlight the main concerns directly linked with the frequent usage of detergents/soaps and alcohol-based hand sanitizers on water quality and the post-pandemic handwashing habits to overcome the COVID-19 spread also threatening the water reserve by high consumption along with more wastewater production with less water reuse efficiency and collectively the pressure on drinking water facilities. This review also focuses on the indirect influence of COVID-19 on water quality through technical interventions among COVID-19, water pollution;soaps/detergents, and hand sanitizer and the complete water management plan for water security and safety from policymakers to end users after the viral revolution briefly.

Recent Advances in the Impact of Infection and Inflammation on Stroke Risk and Outcomes.

PURPOSE OF THE REVIEW: Inflammation is a key component in the pathogenesis of cerebrovascular diseases. In the past few years, the role of systemic infection and gut dysbiosis in modulating inflammation and stroke risk has been increasingly acknowledged. In this review, we synthesize contemporary literature on the effects of infection and inflammation on stroke risk and outcomes, with a focus on periodontal disease, COVID-19 infection, and gut dysbiosis. RECENT FINDINGS: Chronic and acute infections such as periodontitis and COVID-19 induce systemic inflammation that cause atherogenesis and increase cardiac injury and arrhythmias. These infections also directly injure the endothelium leading to worsened secondary inflammation after stroke. Gut dysbiosis engenders a pro-inflammatory state by modulating intestinal lymphocyte populations that can traffic directly to the brain. Additionally, post-stroke immune dysregulation creates a compounding feedback loop of further infections and gut dysbiosis that worsen outcomes. Recent advances in understanding the pathophysiology of how infection and dysbiosis affect the progression of stroke, as well as long-term recovery, have revealed tantalizing glimpses at potential therapeutic targets. We discuss the multidirectional relationship between stroke, infection, and gut dysbiosis, and identify areas for future research to further explore therapeutic opportunities.

Retrospective analysis of NGS data in pediatric genetic cohort: detection of rare variants that may impact influenza and COVID-19 infection

It is difficult to assign a precise frequency of infections that defines an increased susceptibility to infections reflecting an impaired immune response given the majority of patients with intact immune systems still contract multiple upper respiratory infections each year, usually of viral origin. In fact, the average child may experience up to six to eight upper respiratory infections each year. The frequency of these infections may be related to environmental exposures but also may be triggered by genetic susceptibility. As an example, respiratory disease complicates the management of several inherited metabolic diseases, either at presentation or as late-onset features. More recently, children of all ages have been shown to contract COVID-19;however, children with underlying medical conditions are at increased risk. COVID-19 has been known for almost a year now, with several studies identifying genetic risk factors are associated with severe COVID-19. In the context of a health system wide genomic medicine program “Genomic Answers for Kids” at Children’s Mercy, Kansas City, we performed a retrospective analysis of rare variants predicted to be deleterious at 12 known loci known to govern TLR3- and IRF7- dependant type I Interferon immunity of all patients/families (>2000) tested for suspected genetic disorders. We bioinformatically extracted all rare variants in those 12 genes linked to type I interferon pathway from our internal warehouse. From those, ~340 variants were further analyzed based on inheritance, minor allele frequency in population datasets, and in silico prediction. The vast majority of this subgroup of GA4 K patients were referred for a suspected neurological disorder with or without multiple congenital anomalies (~75%). Only 15% were referred for metabolic disorders. Of those, 50% have a known genetic diagnosis unrelated to Immune deficiency. Of the selected index cases, the medical records, and if available the outpatient records, were reviewed to document the occurrence of recurrent infection and/or COVID-19. Preliminary data showed 46 “extremely” rare variants were detected in 37 GA4 K patients;6/37 (16%) have ≥2 in 1–12 genes, one GA4 K patient has 4 “extremely” rare variants in IRF7, and 3/37 GA4 K patients are deceased (~1%). Moreover, a novel disease gene was uncovered in a previously undiagnosed family, of which we identified an additional two affected individuals from an international collaboration. Finally, in a family with apparently dominant transmission of tumid lupus we observe putative causal variant in gene UNC93B1 – linking chronic inflammatory disorder (with known type I interferon association) to mutations predisposing to COVID-19. Recurrent or persistent infection is usually a manifestation of primary immunodeficiency. While most children with recurrent infections have a normal immunity, it is important to remember a subset of patients have an unrecognized genetic susceptibility to infection. Further analysis and monitoring are on-going. As we are continuing to struggle with the COVID-19 pandemic, combined with flu season, understanding precisely who may be at higher risk of infection and complications is critical and could play an important role in ongoing efforts to in disease prevention and the development of better treatment protocols

Retrospective Analysis of Retinal Imaging in COVID-19 Positive Patients at a Tertiary Eye Care Center.

PURPOSE: Since the start of the COVID-19 pandemic, numerous authors have published data demonstrating retinal changes found in patients with COVID-19. However, others have debated the significance of these findings and the effects of COVID-19 on the retina remain uncertain. This study aims to better understand retinal findings in patients with COVID-19. PATIENTS AND METHODS: A retrospective review of patients with a history of a positive COVID-19 polymerase chain reaction test was performed between March 1st, 2020 and October 31st, 2020. Patients were included if they presented within 90 days of their first positive COVID-19 test and underwent color fundus photography and/or OCT of the macula. All images were reviewed by two independent graders who assessed the presence of retinal heme, cotton wool spots, vascular sheathing, and disc edema, as well as hyper-reflective changes, intra-retinal fluid, and sub-retinal fluid on OCT. RESULTS: A total of 119 eyes from 61 patients were included. Among 83 eyes which underwent OCT of the macula, inner retinal hyper-reflective changes were seen in 16.9% (n=14), outer retinal hyper-reflective changes in 18.1% (n=15), intra-retinal fluid in 28.9% (n=24), and sub-retinal fluid in 14.5% (n=12). Among 48 eyes which underwent color fundus photography, retinal hemorrhage was seen in 27.1% (n=13), optic disc edema in 2.1% (n=1), and cotton wool spots in none of the eyes. Sub-analysis of 70 eyes from 41 patients with no alternative retinal pathology to potentially explain the above findings revealed none of the above exam findings on OCT of the macula (n=35), fundus photography (n=28), or documented exam (n=66). CONCLUSION: While a number of patients seen after COVID-19 infection demonstrated retinal findings, all could be explained by pre-existing retinal conditions. In a sub-group of eyes without pre-existing retinal disease, we did not identify any retinal findings that could be associated with COVID-19.

Respiratory disease, and treatment / thematic poster session a novel approach to medical monitoring during the sars-cov-2 pandemic supporting the activ 4b outpatient anticoagulation trial

Rationale The ACTIV 4B (OWS/NHLBI supported) clinical trial addresses the use of anti-platelet and anticoagulant agents in symptomatic COVID-19 positive non-hospitalized patients with regards to safety and prevention of macro- and micro-thrombotic events using a composite outcome (symptomatic DVT/PE, arterial thromboembolism, MI, CVA, hospitalization for CV/pulmonary events, mortality). Concerns regarding SARS-CoV- 2 transmission risk to research staff and overburdened institutional environments create challenges for standard event monitoring. In addition, safety or outcome events often occur at other institutions rather than the enrollment site. Therefore, research methodology was adapted to effectively evaluate and categorize safety events using a remote low touch approach. Methods Trial over can be found at NCT04498273. Potential adverse events identified through patient electronic data capture survey or call center assessments are handled remotely by central clinical study staff. If an event is identified as a possible endpoint or SAE by the central study staff the electronic data collection (EDC) system notifies the central medical monitoring team, and the enrolling site coordinator if patient enrolled from an acute care setting, that additional source documents are necessary. The medical coordinator works with the site coordinator, or will reach out independently to treating institutions to obtain necessary source documents. Based on a review of clinical data from the EDC and all available source documents, final arbitration of seriousness, relatedness and expectedness is be made by the study's Medical Monitor, and appropriate study entities (NIH, FDA, IRB, study leadership, pharmaceutical co.) are notified.Results The process as described has been successfully and effectively implemented in >50 patients with anticipation of 7000 patient eventual enrollment. Events have been captured, source documentation has been procured and events have been reported as per established protocol processes. Conclusion We have effectively implemented a medical safety event monitoring methodology in a “low touch” study design to assess events in the complex COVID-19 outpatient space. Elements of our system can be effectively replicated in other COVID and non-COVID clinical trials. .

Regional Specialty Surgical Practice Efficiencies Gained as a Result of COVID-19.

OBJECTIVE: To identify opportunities for discontinuing elective and nonemergency surgical cases in a regional surgical practice in response to coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: COVID-19 began to affect surgical practices across the United States in March 2020. On March 17, 2020, all elective and nonemergency surgical care was deferred to prepare the Mayo Clinic Health System sites in northwestern Wisconsin for an anticipated surge in patients with COVID-19. When the decision was made to reactivate the surgical practice, several major structural and operational changes were made to the regional surgical practice to optimize efficiencies. RESULTS: The structural and operational changes implemented during reactivation resulted in improved utilization of surgical resources including improvement in operating room (OR) block utilization, increased available OR time, and increased case volumes. CONCLUSION: Surgical and procedural leaders should consider a limited-time deferral of elective surgical cases to implement widespread OR efficiency strategies. The time selected for deferral of surgical cases should target a period of historically low surgical volume to minimize disruption to patient care and impact on overall OR functions.

Evaluation of Transient Ischemic Attack and Minor Stroke: A Rapid Outpatient Model for the COVID-19 Pandemic and Beyond.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients' care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Two Possible Mechanisms of Disease in COVID-19

At the population level, indiscriminate cessation of these drugs would lead to uncontrolled hypertension, heart failure, and other unintended consequences. [...]understanding whether these commonly used drugs truly contribute to mortality in COVID-19 demanded investigation. In their statistical models, older age and heart disease were independently associated with in-hospital mortality, but use of ACE inhibitors and ARBs was not. [...]ACE inhibitors may have been protective.

Missed cerebrovascular events during prolonged sedation for COVID-19 pneumonia.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

Triage considerations for patients referred for structural heart disease intervention during the COVID-19 pandemic: An ACC/SCAI position statement.

The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment, as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.

Role of Teleproctoring in Challenging and Innovative Structural Interventions Amid the COVID-19 Pandemic and Beyond.

Teleproctoring can be used successfully in performing challenging and innovative structural heart interventions using sophisticated technology that allows real-time bidirectional audiovisual communication with digital transmission of live videos and direct observation of the operative field by a remote proctor. The authors share an illustrative case that was performed amid the coronavirus disease-2019 global pandemic that led to travel restrictions to limit spread of the virus. Teleproctoring has future implications beyond the current global health crisis to facilitate rapid dissemination and exchange of knowledge for ultimately helping patients around the globe.