Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following ...vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
-multisystem inflammatory syndrome in children (MIS-C)-which ...comprises multiorgan dysfunction and systemic inflammation
. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections
, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4
CCR7
T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness
and appears distinct from Kawasaki disease.
Background
The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence ...of burnout syndrome amongst intensivists facing the COVID-19 outbreak.
Methods
Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model.
Results
Response rate was 20% (1001 completed questionnaires were returned, 45 years 39–53, 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 1.33–2.55), working in a university-affiliated hospital (HR 0.58 0.42–0.80), living in a city of > 1 million inhabitants (HR 1.40 1.01–1.94), and clinician’s rating of the ethical climate (HR 0.83 0.77–0.90). Independent determinants of depression included female gender (HR 1.63 1.15–2.31) and clinician’s rating of the ethical climate (HR 0.84 0.78–0.92). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year 0.97–0.99) and clinician’s rating of the ethical climate (HR 0.76 0.69–0.82).
Conclusions
The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
Background and Purpose
Platelet function during inflammation is dependent on activation by endogenous nucleotides. Non‐canonical signalling via the P2Y1 receptor is important for these non‐thrombotic ...functions of platelets. However, apart from ADP, the role of other endogenous nucleotides acting as agonists at P2Y1 receptors is unknown. This study compared the effects of ADP, Ap3A, NAD+, ADP‐ribose, and Up4A on platelet functions contributing to inflammation or haemostasis.
Experimental Approach
Platelets obtained from healthy human volunteers were incubated with ADP, Ap3A, NAD+, ADP‐ribose, or Up4A, with aggregation and fibrinogen binding measured (examples of function during haemostasis) or before exposure to fMLP to measure platelet chemotaxis (an inflammatory function). In silico molecular docking of these nucleotides to the binding pocket of P2Y1 receptors was then assessed.
Key Results
Platelet aggregation and binding to fibrinogen induced by ADP was not mimicked by NAD+, ADP‐ribose, and Up4A. However, these endogenous nucleotides induced P2Y1‐dependent platelet chemotaxis, an effect that required RhoA and Rac‐1 activity, but not canonical PLC activity. Analysis of molecular docking of the P2Y1 receptor revealed distinct differences of amino acid interactions and depth of fit within the binding pocket for Ap3A, NAD+, ADP‐ribose, or Up4A compared with ADP.
Conclusion and Implications
Platelet function (aggregation vs motility) can be differentially modulated by biased‐agonist activation of P2Y1 receptors. This may be due to the character of the ligand‐binding pocket interaction. This has implications for future therapeutic strategies aimed to suppress platelet activation during inflammation without affecting haemostasis as is the requirement of current ant‐platelet drugs.
LINKED ARTICLES
This article is part of a themed issue on Platelet purinergic receptor and non‐thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc
A guide to immunotherapy for COVID-19 van de Veerdonk, Frank L; Giamarellos-Bourboulis, Evangelos; Pickkers, Peter ...
Nature medicine,
01/2022, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some ...remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections.
The purpose of this review is to provide an overview of the immune response to major surgery, and the ways in which it may be modulated to improve postoperative outcomes.
Data from patients who have ...undergone a variety of tissue injuries (surgery, burns, sepsis, trauma) have shown the presence of a conserved 'genomic storm' that alters the leukocyte transcriptome, with upregulation of the innate immune response and concomitant downregulation of the adaptive immune response. The innate and adaptive immune systems are often regarded largely distinct. However, more recent evidence suggests there are critical connections between the two arms of the immune response, whereby innate immune cells are able to suppress the adaptive response.
The immune system is critical to the host response to tissue injury occurring due to surgery. However, the physiological processes required to resolve the surgical insult can also contribute to sequelae such as cognitive decline, pneumonia and acute kidney injury. Our understanding of the immune pathogenesis underlying these complications is improving, leading to interest in the development of immunomodulatory therapies, which aim to permit host defence whilst ameliorating postoperative complications.
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