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1.
Transplantation ; 105(10): 2156-2164, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1228581

ABSTRACT

BACKGROUND: The ability of transplant (Tx) patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19 infection. However, analysis of immunity against SARS-CoV-2 is currently lacking. METHODS: Here, we analyzed T cell immunity directed against SARS-CoV-2 spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in 10 Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients. RESULTS: Tx patients (7 renal, 1 lung, and 2 combined pancreas-kidney Txs) were recruited in this study during the acute phase of COVID-19 with a median time after SARS-CoV-2-positivity of 3 and 4 d for non-Tx and Tx patients, respectively. Despite immunosuppression, we detected antiviral CD4+ T cell-response in 90% of Tx patients. SARS-CoV-2-reactive CD4+ T cells produced multiple proinflammatory cytokines, indicating their potential protective capacity. Neutralizing antibody titers did not differ between groups. SARS-CoV-2-reactive CD8+ T cells targeting membrane- and spike-protein were lower in Tx patients, albeit without statistical significance. However, frequencies of anti-nucleocapsid-protein-reactive, and anti-SARS-CoV-2 polyfunctional CD8+ T cells, were similar between patient cohorts. Tx patients showed features of a prematurely aged adaptive immune system, but equal frequencies of SARS-CoV-2-reactive memory T cells. CONCLUSIONS: In conclusion, a polyfunctional T cell immunity directed against SARS-CoV-2 proteins as well as neutralizing antibodies can be generated in Tx patients despite immunosuppression. In comparison to nonimmunosuppressed patients, no differences in humoral and cellular antiviral-immunity were found. Our data presenting the ability to generate SARS-CoV-2-specific immunity in immunosuppressed patients have implications for the handling of SARS-CoV-2-infected Tx patients and raise hopes for effective vaccination in this cohort.


Subject(s)
COVID-19/immunology , Organ Transplantation , SARS-CoV-2/immunology , Adult , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunologic Memory , Male , Middle Aged , T-Lymphocytes/immunology
2.
OMICS ; 25(5): 269-278, 2021 05.
Article in English | MEDLINE | ID: covidwho-1202572

ABSTRACT

With coronavirus disease 19 (COVID-19), we have witnessed a shift from public health to planetary health and a growing recognition of the importance of systems science in developing effective solutions against pandemics in the 21st century. COVID-19 and the history of frequent infectious outbreaks in the last two decades suggest that COVID-19 is likely a dry run for future ecological crises. Now is the right time to plan ahead and deploy the armamentarium of systems science scholarship for planetary health. The science of epigenomics, which investigates both genetic and nongenetic traits regarding heritable phenotypic alterations, and new approaches to understanding genome regulation in humans and pathogens offer veritable prospects to boost the global scientific capacities to innovate therapeutics and diagnostics against novel and existing infectious agents. Several reversible epigenetic alterations, such as chromatin remodeling and histone methylation, control and influence gene expression. COVID-19 lethality is linked, in part, to the cytokine storm, age, and status of the immune system in a given person. Additionally, due to reduced human mobility and daily activities, effects of the pandemic on the environment have been both positive and negative. For example, reduction in environmental pollution and lesser extraction from nature have potential positive corollaries on water and air quality. Negative effects include pollution as plastics and other materials were disposed in unconventional places and spaces in the course of the pandemic. I discuss the opportunities and challenges associated with the science of epigenomics, specifically with an eye to inform and prevent future ecological crises and pandemics that are looming on the horizon in the 21st century. In particular, this article underscores that epigenetics of both viruses and the host may influence virus infectivity and severity of attendant disease.


Subject(s)
COVID-19/genetics , Pandemics , SARS-CoV-2 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Ecology , Environmental Health , Epigenesis, Genetic , Epigenomics , Gene Expression Regulation , Global Health , Host Microbial Interactions/genetics , Humans , SARS-CoV-2/pathogenicity
3.
Brain Behav Immun ; 91: 649-667, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064858

ABSTRACT

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.


Subject(s)
Stroke Rehabilitation/methods , Stroke/immunology , Stroke/physiopathology , Animals , Brain Ischemia/drug therapy , Comorbidity , Disease Models, Animal , Humans , Immunity/immunology , Immunity/physiology , Inflammation/immunology , Neuroprotection/immunology , Neuroprotection/physiology , Outcome Assessment, Health Care , Reperfusion/methods , Reperfusion/trends
5.
Clin Teach ; 18(2): 104-108, 2021 04.
Article in English | MEDLINE | ID: covidwho-814245

ABSTRACT

Attendance at conferences as part of undergraduate studies is key in health professional education for exploring speciality interests, sharing research, exchanging expertise and passing on knowledge. In addition, conferences offer valuable opportunities to present work and the potential to win prizes and network with others in the field. This article provides insight and guidance into how student-led and designed health science and education conferences can be implemented more effectively. It is aimed at students hoping to organise conferences and also to clinical educators and staff who help facilitate these. We present recommendations, a framework of steps to be followed and a case study, as well as an exploration of the challenges that COVID-19 has presented and how these have been overcome.


Subject(s)
COVID-19/epidemiology , Congresses as Topic/organization & administration , Students, Medical , Cooperative Behavior , Feedback , Group Processes , Humans , Interinstitutional Relations , Pandemics , SARS-CoV-2
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