ABSTRACT
Introduction: Type 1 interferon (IFN) autoantibodies, such as anti-IFNalpha, have pathogenic significance in life-threatening COVID-19 pneumonia. Ten to twenty percent of severe COVID cases are associated with type I IFN autoantibodies. These autoantibodies likely pre-exist while others arise de novo relative to SARS-CoV-2 infection. It is unclear to what extent type I anti-IFN autoantibodies are induced by SARS-CoV-2 infection and contribute to COVID-19 severity. We investigated these phenomena in those with inborn errors of immunity (IEI) and rheumatic disease (RHE). Aim(s): We aim to compare the prevalence and neutralization ability of anti-IFNalpha autoantibodies in IEI and RHE patients using archived blood samples before and after the COVID-19 pandemic began. Method(s): We determined the presence of autoantibodies against IFNalpha in plasma samples by enzyme linked immunosorbent assay in 453 patients with IEI or RHE who were testing either before or after the COVID-19 pandemic began in March 2020. Using flow cytometry, we determined the function of IFNalpha autoantibodies in plasma to block CD4T cell activation by inhibiting STAT-1 phosphorylation. Result(s): We found that 25 patients with IEI or RHE were positive for anti-IFNalpha autoantibodies. 10 out of 229 patient samples collected before the pandemic (4.2%) tested positive whereas 15 out of 224 patient samples collected after the pandemic began (7.0%) were positive. Seven of the 25 patients (28%) who tested positive had neutralizing antibodies in plasma, which prevented STAT-1 phosphorylation in CD4T cells;all of these patients had partial recombination activating gene deficiency (pRD) except for one patient with autoimmunity, leukemia and selective IgA deficiency. One pRD patient had anti-IFNalpha autoantibodies with neutralization capacity before the pandemic, which persisted after hematopoietic stem cell transplantation (HSCT) with full immune reconstitution. The patient was immunized for SARS-CoV-2 before and after HSCT and acquired COVID-19 infection a year after HSCT. The patient was symptomatic but never hospitalized and fully recovered despite having anti-IFNalpha autoantibodies. Conclusion(s): Anti-IFNalpha autoantibody levels were comparable before and after the start of the COVID-19 pandemic in IEI and RHE patients but only 28% of cases were neutralizing. The clinical implications of these autoantibodies are yet to be determined.Copyright © 2023 Elsevier Inc.
ABSTRACT
Diosmin is the 7-rutinoside of 3 ', 5,7-trihydroxy-4'-methoxyflavone (7-O-rutinoside of diosmetin), and hespheridine is the 7-rutinoside of 3', 5,7-trihydroxy-4'-methoxyflavanone (7 -O-rutinoside hesperetin). Diosmin, is a gray-yellow or pale-yellow, hygroscopic powder, whereas hesperidine is in the form of light-yellow spherocrystals. Diosmin was isolated from fruits of the Citrus genus (C. sinensis, C. limonia), now it is obtained semi-synthetically from natural hesperidin. These flavonoids have, among others: antimicrobial, anti-inflammatory, anti-diabetic, anti-cancer, analgesic, antioxidant and possibly anti-virus activity, that cause COVID-19. The metabolism of diosmin takes place initially in the small intestine and involves demethoxylation and hydrolysis. In contrast, oxidation and conjugation take place in the liver. There is no presence of diosmin and diosmetin in the urine, which are mainly eliminated in the form of glucuronic acid conjugates. The dominant metabolite detected in urine samples is m-hydroxy-phenylpropionic acid, excreted in conjugated form. Diosmin may reduce the aggregation of Red Blood Cells, and thus it is able to reduce blood viscosity. The LD50 of the mixture of 90% diosmin and 10% hesperidin for rats is over 3 g/kg. The tests did not reveal any mutagenic effects or effects on reproductive functions. It also does not pose a significant threat during breast feeding, as it poorly passes into breast milk.
ABSTRACT
Almost the whole of 2020 was a year of governance by pandemic measures. Many governments, in these extraordinary times, formally introduced states of emergency. One exception in this regard is Poland. Although it used, in the second and third quarter of 2020, one of the most restrictive forms of lockdown, the government did not decide on the declaration of a state of emergency. At the same time, the scope of implemented regulations was extensive. This article presents a qualitative research on the instruments used by the Polish government in the year 2020 to deal with the pandemic. The analysis allows us to conclude that the so called "anti-crisis shields" were used to a large extent as an instrument of governance of the country, not a tool to prevent a pandemic. At least part of the restrictions adopted in Poland was beyond the need and unrelated to fighting the pandemic. However, these steps are leading to further deterioration of the state of democracy. The analysis of the tools used by the Polish government is based on the framework on the democratic backsliding and autocratization as well as the V-dem concept of "autocratization by decree", which can be also applied to the COVID-19 situation.
ABSTRACT
If mental health has become a reactionary concept, much like the notion of public health in the age of the Covid-19 pandemic, then how can critical theory best elaborate a concern for well-being which includes both a psychic and social dimension? This article proposes the concept of existential health to grasp the salubrious zest for life that has been extinguished from social life since March 2020, due to rolling lockdowns and the rise of totalitarian impulses within the medical-industrial complex. It draws on the relational art practice of Lygia Clark along with developments in the psychedelic treatment of addiction to articulate a vision of existential health in an age of mental illness that is irreducible to the specialised domain of psychologists signified by the ‘mental’ in mental health. © 2022 The Philosophy of Education Society of Great Britain.