The Totally Civil Covid Thread.

  • More fallout from lockdowns!!!


    Severe common cold cases increasing among young children may be pegged to COVID-19 lockdowns

    Doctors are noticing an increase in severe cases of the common cold among some children

    Severe common cold cases increasing among young children may be pegged to COVID-19 lockdowns | Fox News


    As children have headed back to school over these last few weeks, doctors have noticed an increase in severe cases of the common cold among some children from two of the most common viruses known to cause the upper respiratory infection: rhinoviruses and enteroviruses.


    That's according to a recent report out of Chicago — though the situation isn't limited to that area


    These viruses typically only cause mild upper respiratory sympto. om. i. h. he. ea. al. lt. th. a. ad. du. ul. lt. ts. lts.

  • On the Record: Time to Reform or Even Better, Replace the World Health Organization


    On the Record: Time to Reform or Even Better, Replace the World Health Organization
    There has been no shortage of examples of the WHO's abysmal performance during the pandemic.  The agency with the mandate to direct and coordinate…
    www.trialsitenews.com


    There has been no shortage of examples of the WHO's abysmal performance during the pandemic. The agency with the mandate to direct and coordinate authority on international health within the United Nations system, adhering to purported value including integrity, professionalism, and respect to diversity not to mention human rights and technical competence has committed one damaging, egregious effort after another.


    Some of their most damaging errors were as follows:


    Claiming China had the outbreak under control without any verification of the situation.

    Delaying the declaration of an International Emergency.

    Advising against travel restrictions to slow the global spread.

    Refusing to declare a Pandemic.

    Claiming Covid-19 was not airborne and only transmitted via fomites and large droplets. Based on these serious errors their guidance was to wash hands frequently and maintain a safe 1meter (later updated to 2meter) distance.

    Strongly advising against the use of life saving corticosteroids for treatment. This was based on low quality evidence gathered during the original SARS epidemic. This erroneous and deadly guidance wasn't corrected until the irrefutable evidence of the RECOVERY trial proved a 35% Risk Reduction in mortality from the corticosteroid, dexamethasone.

    Their confusing guidance on the effectiveness of masking. This guidance was purposely misleading in order to reduce public demand for medical grade masks when PPE was critically short. Purposely misleading the public on critical public health guidance in order to drive a desired behavior will erode all credibility. The message should have been that medical grade masks do reduce transmission but due to the shortage cloth masks should be used by the public in order to conserve medical grade masks for our high-risk healthcare workers.

    The fiasco of the WHO led "Investigation" into the origin of SARS-CoV-2 by including Peter Daszak, head of EcoHealth Alliance on the team, allowing Chinese officials to edit the final report, etc.

    The above is not meant as a comprehensive list but just to illustrate how poorly the WHO responded to the pandemic. Many of these failures directly contributed to a large proportion of the 617million official cases and 6.5million official deaths as of today. The recent Lancet paper discussed many of the WHO failures in their recently published paper.


    One would think that with annual funding of well over $3billion, with the largest contributor being the American taxpayers, the leading International Public Health Agency would have performed much more effectively during this crisis.


    The pandemic has now been raging for over 2.5 years globally. Yet despite all the WHO's catastrophic errors that have been well documented the WHO has failed to either evaluate its own shortcomings or make any sound adjustments to avoid making additional damaging mistakes.


    Another clear example was provided in the WHO's recent guidance change on the use of Monoclonal Antibody treatment against Covid-19. Specifically, the WHO updated their guidance on sotrovimab as well as casirivimab-imdevimab to recommend strongly against the use of these mAbs for the treatment of Covid-19. This was published in the BMJ in the WHO's Rapid Recommendations entitled A living WHO guideline on drugs for covid-19.


    The WHO's guidance is correct to strongly recommend against using these treatments since they are no longer effective against the sub-variants in circulation. Using a mAb which no longer maintains its neutralization potency can actually increase inflammation and cause more severe outcomes. So where is the glaring mistake in the WHO's recent guidance change? It's in their excruciatingly slow response. The NIH and FDA starting limited the use of these therapeutics way back in January 2022 based on published studies (here and here) showing that Omicron and its sub-variants showed dramatic levels of immune escape.


    The NIH and FDA are not known for their agility to respond to new data, but they start to look spry compared to the lumbering global supposed health-friendly bureaucracy. No, the WHO's inexcusable glacial response on this guidance lead to many countries continued use of these expensive and ineffective therapeutics. Possibly Big Pharma benefited but perhaps no one else. Undoubtedly, these therapeutics were at least at times used instead of other options that have proven high efficacy rates such as Paxlovid, Bebtelovimab and Remdesivir. This is just another recent example that the WHO's incompetence is deeply rooted and can't be corrected without a complete restructuring or a replacement of the organization as a whole.


    Credit:


    TrialSite contributor Paul Elkins continues to track unfolding pandemic events, players, and medicinal approaches to help patients. He is based in Orange County.

  • A probe instigated by the French health ministry has found ‘serious malfunctions’ in the laboratory of Didier Raoult, a microbiologist who rose to prominence after suggesting hydroxychloroquine could treat Covid-19.

    Based on Raoult’s small March 2020 study, the then US President Donald Trump repeatedly endorsed hydroxychloroquine, a decades-old cheap malaria drug as a treatment for Covid-19. The study soon came under scrutiny when the International Society of Antimicrobial Chemotherapy, which runs the journal that published the study, distanced itself from it.

    Now the new report has also raised questions about the hydroxychloroquine study. ‘Many of us already suspected that some of the results have not been obtained honestly, [and] that there were differences whenever he did an investigation of a treatment group and a control group,’ says Elisabeth Bik, a microbiologist-turned-scientific-integrity-consultant in California who initially raised the alarm on the hydroxychloroquine study.

    ‘His papers and his pushing of the [hydroxy]chloroquine as a Covid-19 remedy contribute to the idea that vaccines were unnecessary and that the disease was a minor problem, well under control with a cheap pill. Politicians like Bolsonaro and Trump weaponise [these] sort of ideas, further spreading dangerous misinformation,’ says Enrico Bucci, a biologist at Temple University in Philadelphia.

    Didier Raoult

    Source: © Christophe Simon/AFP/Getty Images

    Didier Raoult was singled out for criticism as head of the IHU in a report by France’s health ministry

    According to media reports, a criminal investigation is now underway against Raoult, who was the head of the Hospital-University Institute Mediterranean Infection (IHU) from 2011 until he retired this summer. In June, Raoult’s lab was also sanctioned by France’s National Agency for the Safety of Medicines and Health Products for breaches and non-compliance with regulations covering research on human subjects.

    In 2006, Raoult and four of his co-authors were banned from publishing in journals run by the American Society for Microbiology (ASM) for one year after being accused of image manipulation – a charge that Raoult has vehemently denied over the years.

    Last week, six more papers co-authored by Raoult that were published in ASM journals were flagged with expressions of concern notices. All of the notices state that the paper in question ‘is being reviewed as part of a ‘scientific misconduct investigation’ by the University of Aix Marseille. This expression of concern is issued pending the outcome of the investigation and will be updated accordingly thereafter.’

    The new report found that for many of the IHU studies documenting the health of homeless people, ethical consent was not sought in the participant’s own language. ‘Some of these patients were people who didn’t speak French – foreigners or homeless or migrants – and so those people, according to the French rules, should have been properly informed in their own language,’ Bik explains.

    Last August, Bik penned a blog post highlighting the problems with the research, where she noted that 17 papers spanning 10 years of research at the IHU on homeless people in Marseille, appear to use the same ethical review board approval numbers – another problem also highlighted by the new investigation.

    According to Bik, the new report finds evidence of ‘bullying, verbal violence, humiliation, devaluation, misogynistic remarks, angry behaviour on the part of some heads of department towards students but also staff’ on the part of IHU leadership.

    On 29 April 2021, Raoult filed a criminal complaint against Bik on the basis of attempted blackmail, attempted extortion and aggravated moral harassment. One year on, nothing has come of the complaint, Bik says.

    ‘This is the description of a toxic professional environment, able to substantially pollute science on a vast scale,’ adds Bucci. ‘After reading the report, I would like to use the words of Professor Pierre Tattevin, president of the French Infectious Diseases Society, who said in 2021 that IHU, referred to as “like a sect”, had “lost so much, in terms of scientific dignity, that we hardly see how they could recover”.’

    The report made 16 recommendations including updating the rules governing the appointment and oversight of the institute’s director, strict compliance with these rules and training to preventing harassment.

  • I will leave this hot potato down here, it seems no one wants to touch it.

    How Bill Gates and partners used their clout to control the global Covid response — with little oversight
    Four health organizations, working closely together, spent almost $10 billion on responding to Covid across the world. But they lacked the scrutiny of…
    www.politico.com

    I certainly Hope to see LENR helping humans to blossom, and I'm here to help it happen.

  • Newly Published Data Shows Saline Nasal Irrigation After COVID-19 Diagnosis Can Significantly Reduce Hospitalization, Death

    Newly Published Data Shows Saline Nasal Irrigation After COVID-19 Diagnosis Can Significantly Reduce Hospitalization, Death
    According to researchers associated with the Medical College of Georgia at Augusta University, initiating twice daily flushing of the nasal cavity with a mild…
    www.trialsitenews.com


    According to researchers associated with the Medical College of Georgia at Augusta University, initiating twice daily flushing of the nasal cavity with a mild saline solution soon after testing positive for COVID-19 can significantly reduce hospitalization and death. The published findings have been published in the Ear, Nose & Throat Journal.


    Participants 55 and older were enrolled in the trial within 24 hours of a positive PCR COVID-19 test between September 24 and December 21, 2020. Participants had similar baseline characteristics. Among 826 screened, 79 participants were enrolled and randomly assigned to add povidone-iodine 10% or sodium bicarbonate (baking soda) to 240 mL of saline and nasally irrigate twice daily for 14 days. The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive.


    Researchers found that less than 1.3% of the 79 study subjects were hospitalized and none died. By comparison, 9.47% of patients were hospitalized and 1.5% died in a group with similar demographics reported by the CDC during the same timeframe.


    The investigators found the additives did not add any additional value, however they might help make it more difficult for the virus to attach to the ACE2 receptor.


    The research team also wanted to know any impact of nasal irrigation on symptom severity, including chills and loss of taste and smell. Twenty-three of the 29 participants who consistently irrigated twice daily had zero or one symptom at the end of two weeks compared to 14 of the 33 who did not consistently irrigate. Those who completed nasal irrigation twice daily reported quicker resolution of symptoms regardless of which of two common antiseptics they were adding to the saline water.


    The spiky SARS-CoV-2 protein is known to attach to the ACE2 receptor, which is pervasive throughout the body and in abundance in locations like the nasal cavity, mouth and lungs. Drugs that interfere with the virus' ability to attach to ACE2 have been pursued, and it is thought that nasal irrigation with saline helps decrease the usual robust attachment.


    The publication concludes by stating that irrigation is simple, safe, effective, and inexpensive treatment that can reach across economic and geographic barriers.

  • Now the new report has also raised questions about the hydroxychloroquine study. ‘Many of us already suspected that some of the results have not been obtained honestly, [and] that there were differences whenever he did an investigation of a treatment group and a control group,’ says Elisabeth Bik, a microbiologist-turned-scientific-integrity-consultant in California who initially raised the alarm on the hydroxychloroquine study.

    Please stop repeating the mafia meme. Fauci himself was informed that HCQ works fine long before Raoult and others did use it. HCQ is 100% safe as it is given even to children for tropical holidays. No single drug works perfect for CoV-19. Key is to combine them what Raoult did like all others.


    So lets sum up Raoult and others saved the live of some hundred people where as the Pfizer vaccine simple killed some 100'000. See excess mortality in Australia and many other countries after first "vaccine" cycle. Up to 50% stillbirths of vaxxinated mothers in the first 4 months.


    It's time to point at the Dr. Mengele FM/R/F/B finance/pharma mafia!

  • Covid has many effects on genes and one of those mutated genes is CCYP2R.


    Commentary: Vitamin D status in relation to the clinical outcome of hospitalized COVID-19 patients

    Commentary: Vitamin D status in relation to the clinical outcome of hospitalized COVID-19 patients


    Abstract

    Introduction Vitamin D is a crucial prohormone that mediates a variety of immunological responses. Numerous research findings revealed a strong association between vitamin D deficiency and a higher risk for communicable infections and poor outcomes that could be attributed to the role of vitamin D in regulating immunity (1). While Controversies still persist concerning the plausible role of Vitamin D in COVID-19 disease severity and effect on the outcome; our study demonstrated a significant correlation between severe Vitamin D Deficiency and the risk of a poor disease outcome. We observed a significant link between severe vitamin D deficiency, ICU admission, and COVID-19-related in-hospital mortality (2). In another study from the United Arab Emirates, serum 25(OH)D levels of 12 ng/mL were found to be highly linked with COVID-19 severity and mortality in a sample drawn from a similar population (3). Another research on a different European population from 20 countries, reported that 25(OH)D concentrations and COVID-19 mortality were inversely correlated, and that vitamin D insufficiency was a poor prognostic factor for COVID-19 (4). The reverse causality of the correlation between COVID-19 and the circulating 25(OH)D levels was also explored; Smolders et al. reported a decrease in the circulating 25(OH) D levels caused by the upregulation of the enzyme 25(OH) D1-alpha-hydroxylase as a result of the systemic inflammatory response associated with COVID-19 (5). A retrospective research, investigates the association between pre-infection serum 25-hydroxyvitamin D [25(OH)D] levels and disease severity and death due to SARS-CoV-2, found that pre-infection vitamin D deficiency was associated with increased disease severity and mortality in hospitalized COVID-19 patients (6). A meta-analysis and GRADE review of cohort studies and RCTs, on the other hand, suggested that vitamin D deficiency or insufficiency was not substantially linked to susceptibility to COVID-19 infection or death. The authors further argued that vitamin D supplementation did not improve clinical outcomes in COVID-19 patient (7). Given that supplementation studies are heterogenous in design, controversial results are again anticipated. Genomics-guided tracing research found that vitamin D is involved in regulating gene expression and has the capability to minimize SARS-CoV-2 infection by binding to the vitamin D response element (8). Discussion In a commentary on our study, Speeckaert M and Delanghe J highlighted the potentially essential role of vitamin D binding protein (DBP) and its polymorphism on the link between low vitamin D levels and poor COVID-19 outcome (9). DBP is the main transporter and reservoir for the major vitamin D metabolites which are largely protein bound. There is a significant DBP polymorphism [DBP1S (slow), DBP1F (fast), and DBP2], as well as more than 120 uncommon variants (10). The DBP can be defined by the genetic polymorphisms rs7041 and rs4588 as the C-allele of rs2282679 is related with lower 25(OH)D and DBP levels (11). The observed link in our study could be partially explained by the effect of DBP polymorphism, as carriers of a DBP polymorphism corresponding with lower vitamin D and DBP concentrations might have a higher risk for poor prognosis (9). Furthermore; the polymorphism DBP rs2282679 might account for the majority of the intriguing link as another study suggested (12). Given the debate over the impact of vitamin D status, other researchers found no significant link between vitamin D status and COVID-19 outcome (7). Based on these findings and trying to fit possible explanation, it is very plausible that some genetic factors/polymorphisms may influence vitamin D levels and/or function. These polymorphisms are not just connected to DBP polymorphism, but also include polymorphisms in intermediate metabolites in the vitamin D pathway, vitamin D receptors, and enzymes impacting vitamin D catabolism (13). It could be that while Vitamin D status is sufficient as per our definitions and reference ranges, but due to a polymorphism in vitamin D Receptors- VDR polymorphisms- the function of vitamin D is disrupted, abolished, or minimized, resulting in a status similar to functional vitamin D deficiency, or another polymorphism in the catabolism of vitamin D pathway leading to increased clearance of vitamin D, thereby affecting vitamin d function. Several polymorphisms in genes associated with vitamin D metabolism have been identified as possible risk factors for severe COVID-19 outcomes (14, 15). Analyses of genotype data in connection to vitamin D levels revealed the role of vitamin D homeostasis and its metabolic pathway in determining susceptibility to severe COVID-19 disease. The effect of vitamin D in host immunity against SARS-CoV-2 and other viral infections may explain these genotypic disparities in COVID-19 disease outcome (16, 17). Al Anouti et al. investigated the genetic contribution of specific haplotypes for VDR, DHCR7/NADSYN1, and GC genes in to COVID-19 disease severity among the UAE population in a study that focused on the associations between genetic variants in the Vitamin D metabolism pathway and severity of COVID-19. The AA genotype in SNP rs59241277, the CC genotype in SNP rs113574864, the GG genotype in SNP rs182901986, the TT genotype in SNP rs60349934, and the GG genotype in SNP rs113876500 in gene GC, for example, were all linked to the critical COVID-19 condition (13). Vitamin D metabolism is also mediated by several cytochrome P450 enzymes. CYP2R1 is one of the enzymes involved in vitamin D hydroxylation (18). Several studies have been conducted to examine the relationship between CYP2R1 genetic variants and vitamin D status in different populations, and these investigations concluded that a strong correlation existed between specific polymorphisms on SNPs (rs10766197 and rs10741657) and the risk of vitamin D deficiency (19, 20). On the other hand, Apaydin et al. found that 25 (OH)D levels were unrelated to COVID-19 severity and mortality, while VDR gene polymorphisms were significantly correlated with COVID-19 severity and patient survival (21). The majority of the people in our survey were South Asians, not Arabs. One study from Kuwait found that CYP2R1 SNPs (rs10500804 and rs12794714) were substantially linked with serum 25(OH)D levels in the Arabian group but not in the South Asians (22). The same results were discovered in another study derived from a similar population to our study (13). This could be explained by several complicated interactive effects of distinct polymorphisms in the vitamin D metabolic pathway, which significantly impact both its level and function. This result suggests that not only DBP variations, but also all vitamin D Metabolic pathway associated genes, might have a role in COVID-19 disease prognosis and transmission. One plausible explanation- at least partially -for the debates around vitamin D's link to COVID-19 outcome could be the effect of such various polymorphisms in each study cohort on altering this effect among different populations. Even supplementation responses could be modulated by the genetic variations with DBP and other Vitamin D metabolism genes. The effect of Common polymorphisms of DBP on vitamin D supplementation was studied by Al-Daghri et al., who concluded that 25[OH]D concentrations were significantly higher among people with the major homozygous rs7041 genotype while 25[OH]D was higher in participants carrying homozygous major genotypes in rs4588 and rs7041 compared to other genotypes after supplementation (23). Furthermore, the optimal level of vitamin D may range from one community to others dependent on the distribution of such polymorphisms in different populations. These probable causes should be acknowledged for future research, and vitamin D effect could be appropriately examined in the context of the distribution of vitamin D metabolism related genes variation in different populations. Conclusion While DBP polymorphisms may be involved in the link between vitamin D status and COVID-19 outcome, many other polymorphisms in Vitamin D metabolic pathway genes might also be involved, and future research should acknowledge investigating vitamin D status in the context of such polymorphism distribution in each study population, and proper vitamin D levels should be estimated taking these polymorphisms into consideration. Author contributions The author confirms being the sole contributor of this work and has approved it for publication. Conflict of interest The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


    Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase

    https://www.pnas.org/doi/10.1073/pnas.0402490101


    CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency

    CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency
    Production of the active vitamin D hormone 1,25-dihydroxyvitamin D requires hepatic 25-hydroxylation of vitamin D. The CYP2R1 gene encodes the principal…
    www.ncbi.nlm.nih.gov


    CYP2R1 cytochrome P450 family 2 subfamily R member 1 [ Homo sapiens (human

    CYP2R1 cytochrome P450 family 2 subfamily R member 1 [Homo sapiens (human)] - Gene - NCBI

  • It's all about vitamin D


    Metabolic rewiring and serotonin depletion in patients with postacute sequelae of COVID-19

    https://onlinelibrary.wiley.com/doi/10.1111/all.15253


    Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only causes acute coronavirus 2019 (COVID-19) disease but also can lead to significant long-term effects that impact daily functioning and quality of life, termed postacute sequelae of COVID-19 (PASC).1 The most frequently reported symptoms include fatigue, cognitive dysfunction, and memory issues, but multisystem involvement and significant disability are also common.2 Despite the rapid accumulation of knowledge on the acute phase of COVID-19, a limited number of studies are currently available that examine the pathophysiology of PASC, particularly in relation to fatigue. Mechanisms are thought to include the direct consequences of viral infection, severe systemic inflammation, oxidative stress, neuroinflammation, microvascular thrombosis, and neurodegeneration processes. We previously showed that levels of multiple cytokines, including TH2 cytokines such as interleukin (IL)-4, macrophage-derived chemokine (MDC), and thymic stromal lymphopoietin (TSLP), remained elevated for an extended period of time following SARS-CoV-2 infection.3 In this study, our aim was to identify additional potential novel mechanisms of disease, by investigating changes in metabolism that associate with PASC.



    Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior

    Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior - PubMed
    Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory…
    pubmed.ncbi.nlm.nih.gov


    Abstract

    Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction


    CYP2R1 SUMMARY

    CYP2R1 protein expression summary - The Human Protein Atlas

    A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol) 1, 2, 3. Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives 4, 5. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) 6, 7, 8. show less

    Molecular function (UniProt)i Monooxygenase, Oxidoreductase

    Disease involvementi Disease variant

    Ligand (UniProt)i Heme, Iron, Metal-binding

    Gene summary (Entrez)i This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into the active ligand for the vitamin D receptor. A mutation in this gene has been associated with selective 25-hydroxyvitamin D deficiency.


    Impact of SARS-CoV-2 Infection (COVID-19) on Cytochromes P450 Activity Assessed by the Geneva Cocktail

    https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2412

    Abstract

    Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a severe acute respiratory syndrome with an underlying inflammatory state. We have previously demonstrated that acute inflammation modulates cytochromes P450 (CYPs) activity in an isoform-specific manner. We therefore hypothesized that COVID-19 might also impact CYP activity, and thus aimed to evaluate the impact of acute inflammation in the context of SARS-CoV-2 infection on the six main human CYPs activity. This prospective observational study was conducted in 28 patients hospitalized at the Geneva University Hospitals (Switzerland) with a diagnosis of moderate to severe COVID-19. They received the Geneva phenotyping cocktail orally during the first 72 hours of hospitalization and after 3 months. Capillary blood samples were collected 2 hours after cocktail administration to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were also measured in blood. CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (P = 0.0001), 74.7% (P = 0.0006), and 22.8% (P = 0.045), respectively, in patients with COVID-19. CYP2B6 and CYP2C9 MRs increased by 101.1% (P = 0.009) and 55.8% (P = 0.0006), respectively. CYP2D6 MR variation did not reach statistical significance (P = 0.072). As expected, COVID-19 was a good acute inflammation model as mean serum levels of CRP, IL-6, and TNF-α were significantly (P < 0.001) higher during SARS-CoV-2 infection. CYP activity are modulated in an isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of CYP substrates, whether used to treat the disease or as the usual treatment of patients, could be therefore clinically impacted.

  • Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells


    Abstract

    Many therapeutic antibodies (Abs) and mRNA vaccines, both targeting SARS-CoV-2 spike protein (S-protein), have been developed and approved in order to combat the ongoing COVID-19 pandemic. In consideration of these developments, a common concern has been the potential for Ab-dependent enhancement (ADE) of infection caused by inoculated or induced Abs. Although the preventive and therapeutic effects of these Abs are obvious, little attention has been paid to the influence of the remaining and dwindling anti-S-protein Abs in vivo. Here, we demonstrate that certain monoclonal Abs (mAbs) approved as therapeutic neutralizing anti-S-protein mAbs for human usage have the potential to cause ADE in a narrow range of Ab concentrations. Although sera collected from mRNA-vaccinated individuals exhibited neutralizing activity, some sera gradually exhibited dominance of ADE activity in a time-dependent manner. None of the sera examined exhibited neutralizing activity against infection with the Omicron strain. Rather, some ADE of Omicron infection was observed in some sera. These results suggest the possible emergence of adverse effects caused by these Abs in addition to the therapeutic or preventive effect.



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  • Vitamin D and morbidity in children with Multisystem inflammatory syndrome related to Covid-19

    Vitamin D and morbidity in children with Multisystem inflammatory syndrome related to Covid-19
    Multisystem inflammatory syndrome (MIS-C) is a clinical presentation reported in children related to Coronavirus-19 infection who present with a toxic…
    www.sciencedirect.com


    Highlights

    Multisystem Inflammatory Syndrome in Children (MIS-C) has been related to a late presentation of Covid-19 infection.


    Previous studies in critically ill children have shown an association between severe disease and vitamin D deficiency.


    We report a possible association between severe vitamin D deficiency and severe disease in children with MIS-C.


    Severe vitamin D deficiency was associated with cardiac involvement, prolonged ICU, and hospital length of stay.



    Abstract

    Background

    Multisystem inflammatory syndrome (MIS-C) is a clinical presentation reported in children related to Coronavirus-19 infection who present with a toxic shock like syndrome. Vitamin D deficiency has been postulated to play a role with severity of coronavirus infection in adult patients and other viral respiratory infections.


    Objective

    This study aims to investigate if severe vitamin D deficiency was associated with increased disease severity and cardiac involvement in MIS-C.


    Methods

    This is a retrospective and single center study. We included hospitalized patients less than 18 years of age with diagnosis of MIS-C between March and July 2020. Severe vitamin D deficiency was defined as 25-OH vitamin D level < 10 ng/ml within 48 h of admission. The composite outcome severe disease included patients requiring inotropes, mechanical ventilation, and extracorporeal membrane oxygenation.


    Results

    Of the 31 patients with MIS-C, 45% were male and 58% were African American. The median age was 8 (1–13) years. Ten patients had severe vitamin D deficiency with a mean level of 7.2 ng/ml. Ninety percent of patients with severe vitamin D deficiency had severe disease (P < 0.001). Patients with severe vitamin D deficiency had an increased risk of cardiac involvement (P < 0.001).


    Conclusions

    We describe a potential association between severe vitamin D deficiency and severe disease in children presenting with MIS-C. Severe vitamin D deficiency predisposes patients for cardiovascular involvement and may play a critical role in the host immune response to COVID-19 infection. Future prospective studies at the basic science and clinical level should be pursued to better delineate this association.

  • I think your are completely misrepresenting the stance of John Campbell. If you care enough to watch his channel videos since the beginning of the pandemic, and since the beginning of the jab roll out, he was a staunch and enthusiastic advocate for these jabs, even if he always recommended a preventive approach based in Vit. D.

    His staunch support, however, begun cracking around 5 months ago where he began to analyze the FOIA released documents about the Pfizer trials. He even backpedaled a few weeks later, But then The statistics and papers, as he always bases his analysis in those, began to see problems again, And then YouTube started censoring him.

    I agree that he is not a standard antivaxxer. But in his early comments on anti-viral drugs he showed poor judgement and an inability to understand what studies mean. He seems to have gradually got sucked into an attractive but unevidenced (except by misreading of studies) antivaxxer meme. He has no background in this area - and so I see his views as of no value. He is however a good publicist and does nice youtube videos.


    I have not every seen any sophistication or ability to do useful data analysis from him - so I think his "analysis" of statistics is not valuable. Whereas others have done that detailed work on the same data (with different conclusions).


    I think he believes what he says. I think he has (as would be expected form his training and work) very little scientific or mathematical understanding. It leaves him vulnerable.

  • PayPal bans Free Speech and Sceptics


    Following EU, UK, US Gov't orders?


    PayPal shuts account of parents’ group that campaigned to keep schools open during pandemic


    UsForThem said it has been unable to access thousands of pounds in donations ‘due to the nature of our activities’


    It comes as PayPal faces a backlash over its decision to shut down the accounts of the Free Speech Union, its founder Toby Young and his news and opinion website, the Daily Sceptic.


    Other groups which have said their accounts have recently been shut down by PayPal include Left Lockdown Sceptics, which describes itself as a “socialist collective” opposed to government lockdown measures


    https://www.telegraph.co.uk/news/2022/09/21/paypal-shuts-account-parents-group-campaigned-keep-schools-open/

    Or

    archive.ph

  • News Round-Up - H/T DS



    Steve Kirsch welcomes him to the club, and wonders if he’ll be interested in the leaked Israeli vaccine safety data.



    Adverse Effects of the Pfizer Vaccine Covered Up by the Israeli Ministry of Health ⋆ Brownstone Institute
    So if Israel did not in fact have a functioning adverse event monitoring system in place and its data was a fiction, and even if when it did launch a proper…
    brownstone.org


    Yaffa Shir-Raz writes asking: “If Israel did not in fact have a functioning adverse event monitoring system in place and its data was a fiction, and even if when it did launch a proper monitoring system a year too late, with analysis of the system’s findings completely ignored and withheld – what was the FDA really relying on?”




    D. V. Williamson takes a look at the mortality data.

    The Fiction of ‘Sudden Adult Death Syndrome’ – A Graphical Essay
    By March of 2022, rates of mortality appeared to have reverted to normal, but a closer look reveals all age cohorts have paid a heavy price over the course of…
    dvwilliamson.substack.com


    It was only in March 2021 that excess mortality among the most elderly finally turned sharply negative. Basically, it looks like COVID had finally burned through that population by March 2021. Burning through the population would have amounted to taking away the most vulnerable, in which case the population that remains would end up being healthier. In turn, total fatalities should decline sharply; excess mortality should turn negative. But then...



    This is the biggest coverup in the history of science

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  • Dr. Campell has been - more or less - silenced by the FM/R/F Youtube mafia that helps selling deadly gene tech cures.


    Record excess deaths in Europe
    European Union, Excess mortality hits +16%, highest 2022 value so farUK latest excess death data, updated 16th Septemberhttps://www.ons.gov.uk/peoplepopulati...
    www.youtube.com


    Google/Youtube/Putin what is the difference for free speech about facts?

  • UK COVID-19 Vaccination Injuries Fact Check

    UK COVID-19 Vaccination Injuries Fact Check
    The&nbsp;Office of National Statistics&nbsp;(ONS), the UK&rsquo;s official agency for collecting statistics, published death statistics with the vaccination…
    www.trialsitenews.com


    The Office of National Statistics (ONS), the UK’s official agency for collecting statistics, published death statistics with the vaccination status of the deceased individuals from January 1, 2021, to May 31, 2022. This information also showed how many weeks had passed from the time of vaccination to the time of death. The ONS categorized the death reports into those who had a COVID-19 infection, and those who did not. The reliability of the ONS is questioned in an article featured on TrialSite regarding data manipulation.


    The ONS disclosed that 70,784 vaccinated individuals were omitted from the death statistics due to what ONS referred to as “erroneous or inconsistent vaccination data.” For example, a death report that was missing a second-vaccine dose but included the first and third-vaccine dose is labeled as “erroneous or inconsistent” vaccination data and omitted from the death statistics. According to the agency, it is not common practice for the death reports to include the vaccination status of the deceased. The reported numbers give empirical indications, which call for further scrutiny. This is especially so because the real numbers could in all probability be much higher than those in the statistics.


    Is the ONS Making the Mortality Numbers of Those Vaccinated Hard to Read?

    To their credit, the ONS makes critical statistics publicly available, and goes a step further to categorize data into vital groups. The presentation of the numbers makes it tricky for the public to understand at a glance, because it entails nine tables of raw data in Excel sheets. This requires some analysis to tally and interpret the numbers into information that can be used for the COVID-19 guidelines. In addition to this, earlier concerns of miscategorization of vaccination status in relation to UK death reports can cause confusion on how to interpret the numbers in the ONS.


    To get a better understanding of data and emerging patterns in vaccinated and unvaccinated individuals, one would have to dig deeper, carry out analyses, and corroborate with other reports from the Yellow Card reports and ongoing research. Perhaps, it would be useful for government health agencies and surveillance systems to collaborate and give the public clear answers that are not divergent or steeped in ambiguity.


    However, for a basic tally, all numbers of deaths in the vaccinated at one week, two weeks, three weeks, four weeks, and so on from the time of receiving the COVID-19 vaccine can be a starting point.


    Are the Numbers Alarming?

    The May ONS dataset showed that almost 70,000 deaths were reported that had occurred within four weeks of vaccination, and almost 159,000 at eight weeks after vaccination as of May 2022. The agency clarified that the March 2022 statistics contained some errors of wrong entries and published revised numbers. It also acknowledged that these are provisional numbers, and it may add more as they are reported. Note, that the ONS simply published the deaths by vaccination status of the individual dating from January 2021 and did not link the vaccination.


    Unanswered Questions Abound

    The ONS stated that the lowest number of deaths were in those who had a third dose of the vaccine, supporting recommendations of boosters. A study showed that the triple vaccinated had the highest rates of infection from the contagious but mild Omicron variants. This is notable because reportedly, the Omicron wave caused more deaths than Delta. However, it is not clear if the triple vaccinated suffered the highest mortality rates overall.


    Answers are necessary for salient information that could provide direction to re-examine the vaccine guidelines and update health policy. It is also necessary for the public to get full disclosure on the advantages or disadvantages of government guidelines on COVID-19 vaccines. Unknown information includes what vaccines were administered to the individuals in these statistics, what the percentages of each vaccine used were, and what dominant variant was in circulation at the time of most deaths.


    Perpetual Boosters?

    The government’s Joint Committee on Vaccination and Immunization (JCVI) issued more recommendations for the elderly and the immunosuppressed to receive an additional spring COVID-19 booster vaccine and another autumn booster later in the year. This would be a booster from either the Spikevax or Comirnaty vaccine. It is unknown if the immunization committee will keep rolling out booster recommendations every season. During the Omicron wave, the advisory committee’s answer to breakthrough infections was to reduce the time interval between primary and booster vaccination.


    The big question on boosters is this: Is the government using updated evidence-based science in formulating their recommendations? If not, what do the Yellow Card reports and current research mean to the advisory committees in terms of efficacy and safety?


    It remains to be seen if evidence-based research will be the government experts’ true north for direction on COVID-19 advisory guidelines. Accuracy, timeliness, and objectivity in reporting statistics by ONS are necessary in its function as an independent institution. This information is useful in giving critical information to the experts for their decision-making in serving the public.

  • elderly with previous Covid infection more likely to come down with Alzheimer's. Not surprising after the posts I've provided over the last 2 weeks. Vitamin D is the key to a long healthy life.


    Vitamin D and the risk of dementia and Alzheimer disease


    Vitamin D and the risk of dementia and Alzheimer disease
    Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.…
    n.neurology.org


    Abstract

    Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.


    Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria.


    Results: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.


    Conclusion: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.