Fifth Dose of COVID Vaccine Fails to Boost

Posted by zedie

The COVID-19 vaccines may weaken our ability to fight viruses at the cellular level.

Many people may be aware that neutralizing antibodies significantly wane after only a few months following COVID-19 vaccination. Newly emerging subvariants have developed a solid ability to escape from neutralizing antibodies.

However, another significant facet of the COVID-19 vaccine is that it can damage our cellular immunity, especially T-cell immunity. Cellular immunity, or cell-mediated immunity, does not involve antibodies and is pivotal in preventing the severe form of COVID-19. Recent evidence shows that after a fifth vaccine booster dose, cellular immunity waned as well.

Fifth Dose Fails to Strengthen Cell Immunity

A study, published in Frontier Immunology looked at the long-term impact of the COVID-19 mRNA vaccine on cellular immunity.

The immune responses of 61 subjects who received five doses of the vaccine were tracked from 2021 to 2023. The first four doses were the Pfizer monovalent mRNA vaccine, and the fifth dose was the Pfizer-BioNTech bivalent vaccine (Comirnaty Bivalent Original/Omicron BA.4/5).

All subjects were on hemodialysis and at high risk for severe COVID-19. The average age was 70 years. About 90 percent (55), had high blood pressure, almost half (30) had diabetes, and a smaller group of about 11.5 percent (7), had dyslipidemia, which is an abnormal amount of lipids in the blood. For their third vaccine dose, 26.2 percent of the participants (16) received a different type of vaccine booster, specifically Moderna (mRNA-1273).

The study found that while most patients maintained a strong antibody response (humoral immunity), their immune cell-based defense, as measured by interferon production T-cell immunity, weakened in many cases. After the fifth vaccine dose, only half of the patients maintained strong cellular immunity. Older participants, those aged 70 and above, were more likely to have a slightly weaker cellular immune response.

The proportion of vaccinated people who acquired cellular immunity was 75.4 percent at 10 months post-first dose, with a slight increase to 87.5 percent one month following the fourth dose; however, after the fifth dose, cellular immunity decreased significantly from 58.6 percent at one month to 50 percent at three months.

Importance of Cellular Immunity

Our immune system is composed of natural immunity and adaptive immunity. Natural immunity is the body’s inborn ability to fight off broad-spectrum infections, regardless of the specific type of virus, while adaptive immunity is the body’s second line of defense against particular invaders.

Adaptive immunity is executed by specialized immune cells that respond to specific viruses. These include lymphocytes—white blood cells such as T cells, B cells, and natural killer cells.

Our B cells are like “antibody factories” and are responsible for producing virus-specific antibodies to neutralize a virus.

T cells are a diverse group with several roles. Some act like team leaders, helping other cells do their jobs and coordinating the entire immune response; these are known as “T helper cells.” There are also “cytotoxic T cells,” known as “killer T cells,“ which specialize in destroying infected cells. Additionally, there are ”regulatory T cells,” which help regulate the immune system response by suppressing the actions of other cells.

Studies have found that new variants of SARS-CoV-2 can dodge the immune response created by mRNA vaccines, but they can’t escape T-cell-associated defense.

Interferon: A Powerful Antiviral Weapon

Cellular immunity is part of adaptive immunity that responds via T cells and B cells, etc., and mucosal immunity is part of our innate immunity (e.g., the skin and nose). Both types of immunity use interferon as a potent antiviral weapon to fight against a virus.

In mucosal immunity, when our body is confronted with a virus at the epithelial layer (surface layer of the mucosa), the epithelial cells can produce interferon, helping the cells enter an antiviral state to eradicate the virus effectively before it spreads deeply into our body. When interferon is produced naturally via our mucosa, it’s the most effective way our body eradicates a virus at the frontline. This is not possible with commonly used injected vaccinations.

In cellular immunity, interferons also act as a powerful secret weapon and play a pivotal role in antiviral immunity by eradicating pathogens.

Interferon can be reproduced by killer T cells and natural killer cells during viral infection to maximize its antiviral effects. This early and rapid increase of killer T-cell activity may explain why some people don’t experience symptoms of COVID-19 infection.

A 2023 study found that those who experienced infection had significantly lower levels of interferons compared to uninfected participants. Furthermore, participants with a significantly higher level of cellular immunity were less likely to develop breakthrough infections after vaccination.

A study published in Cell Reports shows that during the early stages of a COVID-19 infection, if a person can quickly generate SARS-CoV-2- specific T cells or interferon-producing T cells, the body can get rid of the virus faster, resulting in a less severe case of COVID-19.

The researchers analyzed the virological and immunological changes in 12 patients with acute SARS-CoV-2 infection from disease onset through recovery or death and found that patients with only mild symptoms had an early induction of interferon-gamma-secreting SARS-CoV-2-specific T cells.

mRNA Vaccines Weaken Cellular Immunity

Some may wonder how COVID-19 mRNA vaccines can suppress our cellular immunity. Here are some plausible explanations.

Spike Protein

COVID-19 vaccines bypass our body’s mucosal and vascular barriers when injected into the deltoid muscle. How our immunity responds to a vaccine will determine the impact of the vaccination.

The spike protein in mRNA vaccines is known to dysregulate our normal antiviral immunity. A study found that at 28 days after vaccination, spike protein caused consistent alteration of gene expression in peripheral immune cells, resulting in impaired interferon responses and suppressed cellular immunity, including lymphocyte and monocyte suppression.

The spike protein from the vaccine doesn’t break down quickly and can circulate in the body for over four months, which can negatively impact our immunity.

Modified mRNA

The mRNA vaccines use a slightly altered genetic code, which includes something called N1-methylpseudouridine instead of the usual uracil. This change has been found to cause regulatory T cells to activate in a way that suppresses cellular immunity.

These modified mRNA particles go to specific cells in the spleen responsible for presenting antigens without triggering necessary co-stimulatory immune responses. This will cause a decrease in the number of functioning T cells and an increase in regulatory T cells, resulting in impaired cellular immunity.

Lipid Nanoparticles

The vaccine’s ingredients include lipid nanoparticles (LNPs), tiny fat-like particles that can gather in various organs like the liver and the spleen. These LNPs, along with the mRNA they carry, can cause further inflammation, resulting in dysregulated cellular immunity.

Blood Vessel Injury

The antibodies our bodies produce in response to the vaccine’s spike protein might accidentally harm cells and tissues creating spike proteins. This includes damage to the endothelial cells, which line our blood vessels and could potentially harm organs vital to our immunity, like the adrenal gland.

Antibody-Dependent Enhancement and Immune Imprint

Another possibility known as antibody-dependent enhancement, can wreak havoc on the normal function of cellular immunity.

This could occur when the immune system’s memory of the original Wuhan-type vaccine interferes with its ability to fight off new variants, making the vaccine ineffective against these variants, potentially strengthening the COVID-19 virus’s ability to replicate.

New Variants Escape T-cell Immunity

Starting from Omicron emergence, this SARS-CoV-2 variant family has learned to escape from B cell immunity with vastly increased infectivity and immune escape from spike protein-induced antibodies. Recent variants (e.g., JN.1) have learned to mutate in the non-spike regions to escape original T-cell immunity. This could make it more challenging for our original cellular immunity to eradicate an Omicron variant.

In summary, the extensive promotion of the COVID-19 vaccine has had significant long-term negative consequences, necessitating a thorough and objective reassessment of whether we should continue to encourage vaccination among the population. Relying solely on blind faith or irrational beliefs in this context can be counterproductive and potentially harmful. Health authorities and public officials have been calling for a complete discontinuation of all mRNA vaccines.

It’s also crucial to highlight the value of non-pharmacological preventive measures and primary health education about our immune system’s role in combating viruses. There are numerous ways to holistically boost our endowed immunity based on modern biomedical research. Such knowledge is essential and should be given due attention by health authorities. This approach empowers individuals with vital information and should be a part of a comprehensive public health strategy.

Association Between Daily Toothbrushing and Hospital-Acquired PneumoniaA Systematic Review and Meta-Analysis

Posted by zedie

Key Points

Question Is daily toothbrushing among hospitalized patients associated with prevention of hospital-acquired pneumonia and improved objective outcomes?

Findings This systematic review and meta-analysis of 15 randomized clinical trials with an effective population size of 2786 patients found that hospital-acquired pneumonia rates were lower among patients randomized to daily toothbrushing, particularly among patients receiving invasive mechanical ventilation. Toothbrushing was also associated with shorter duration of mechanical ventilation, shorter intensive care unit (ICU) length of stay, and lower ICU mortality, whereas hospital length of stay and use of antibiotics showed no differences.

Meaning These findings suggest that daily toothbrushing may be associated with lower rates of pneumonia and ICU mortality, particularly among patients undergoing invasive mechanical ventilation; programs and policies to encourage daily toothbrushing are warranted.

Abstract

Importance Hospital-acquired pneumonia (HAP) is the most common and morbid health care–associated infection, but limited data on effective prevention strategies are available.

Objective To determine whether daily toothbrushing is associated with lower rates of HAP and other patient-relevant outcomes.

Data Sources A search of PubMed, Embase, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and 3 trial registries was performed from inception through March 9, 2023.

Study Selection Randomized clinical trials of hospitalized adults comparing daily oral care with toothbrushing vs regimens without toothbrushing.

Data Extraction and Synthesis Data extraction and risk of bias assessments were performed in duplicate. Meta-analysis was performed using random-effects models.

Main Outcomes and Measures The primary outcome of this systematic review and meta-analysis was HAP. Secondary outcomes included hospital and intensive care unit (ICU) mortality, duration of mechanical ventilation, ICU and hospital lengths of stay, and use of antibiotics. Subgroups included patients who received invasive mechanical ventilation vs those who did not, toothbrushing twice daily vs more frequently, toothbrushing provided by dental professionals vs general nursing staff, electric vs manual toothbrushing, and studies at low vs high risk of bias.

Results A total of 15 trials met inclusion criteria, including 10 742 patients (2033 in the ICU and 8709 in non-ICU departments; effective population size was 2786 after shrinking the population to account for 1 cluster randomized trial in non-ICU patients). Toothbrushing was associated with significantly lower risk for HAP (risk ratio [RR], 0.67 [95% CI, 0.56-0.81]) and ICU mortality (RR, 0.81 [95% CI, 0.69-0.95]). Reduction in pneumonia incidence was significant for patients receiving invasive mechanical ventilation (RR, 0.68 [95% CI, 0.57-0.82) but not for patients who were not receiving invasive mechanical ventilation (RR, 0.32 [95% CI, 0.05-2.02]). Toothbrushing for patients in the ICU was associated with fewer days of mechanical ventilation (mean difference, −1.24 [95% CI, −2.42 to −0.06] days) and a shorter ICU length of stay (mean difference, −1.78 [95% CI, −2.85 to −0.70] days). Brushing twice a day vs more frequent intervals was associated with similar effect estimates. Results were consistent in a sensitivity analysis restricted to 7 studies at low risk of bias (1367 patients). Non-ICU hospital length of stay and use of antibiotics were not associated with toothbrushing.

Conclusions The findings of this systematic review and meta-analysis suggest that daily toothbrushing may be associated with significantly lower rates of HAP, particularly in patients receiving mechanical ventilation, lower rates of ICU mortality, shorter duration of mechanical ventilation, and shorter ICU length of stay. Policies and programs encouraging more widespread and consistent toothbrushing are warranted.

Unclear if Chronic Cough Drug Has Meaningful Benefit, FDA Reviewers Say

Posted by zedie

Previously rejected gefapixant will face agency’s panel of outside experts on Friday

FDA ADCOMM gefapixant oral tablets over a photo of a mature man coughing.

It remains “unclear” whether the modest effects of gefapixant, an investigational drug for chronic cough, represent a clinically meaningful benefit, said FDA staff ahead of a meeting of the agency’s Pulmonary-Allergy Drugs Advisory Committeeopens in a new tab or window.

On Friday, committee members will wrestle with exactly what constitutes a meaningful benefit for this incredibly common condition, as no threshold has been established, and whether the P2X3 receptor antagonist’s impact would even be perceptible to patients.

Last year, FDA rejected gefapixant for the proposed indicationopens in a new tab or window of treating refractory or unexplained chronic cough in adults. Beyond concerns about the drug’s modest effect, the agency took issue with the measurement system used to track patients’ coughs in the two pivotal trials and requested additional data — essentially asking that sponsor Merck recount coughing frequency with a different methodology.

In the new recount analyses requested by FDA, gefapixant at a 45-mg dose showed a 15-17% relative reduction in 24-hour cough frequency over placebo at weeks 12 and 24 (the two phase III trials’ primary endpoints, though the difference was significant in only one of them). The trials were designed to show a 30% reduction.

Subsequent analyses to better understand the treatment effect failed to move the needle, according to the agency reviewers. “Assessed a variety of ways, the reduction in cough frequency was consistently small,” they wrote in their briefing documentsopens in a new tab or window for the meeting.

Other concerns raised in the pre-meeting package included interpretation of supporting patient-reported outcome (PRO) data, and the potential unblinding of patients as a result of taste disturbance. That common side effect of gefapixant occurred in 65% of study participants and was a cause of early treatment discontinuation in 14%.

No therapies are currently approved to treat chronic cough, which affects an estimated 5% to 10% of all adults. It is considered refractory when not relieved by treatment for an existing condition that causes coughing — such as chronic obstructive pulmonary disease (COPD) or asthma — or simply unexplained when no underlying medical condition is present.

A host of products are used off-label for the condition (neuroleptics, opioids, local anesthetics), but they can carry risks and evidence supporting their use is limited. “As such, FDA anticipates that a new product approved for [chronic cough] will be widely used given the prevalence of the condition and lack of therapeutic options,” the agency reviewers wrote, noting that long-term treatment would be anticipated.

While the exact cause of chronic cough is unclear, “a variety of nociceptors (including purinergic receptors such as P2X3) and mechanoreceptors have been implicated as ‘cough receptors’ in the respiratory mucosa, which respond to both intrinsic and extrinsic noxious stimuli, as well as mechanical stimulation,” wrote agency staff. “As an antagonist of the P2X3 receptor, which is expressed on sensory neurons in the afferent limb of the cough reflex, gefapixant is hypothesized to ameliorate this increased sensitivity to noxious stimuli, which could suppress the cough reflex.”

Beyond the issues with the primary endpoint in the pivotal trials, secondary endpoints did not provide additional support for gefapixant’s effect on coughing frequency, according to the document, though some PRO data did suggest patient improvement.

In one of the trials, a significantly higher proportion of patients had a 1.3-point or greater increase on the Leicester Cough Questionnaire total score from baseline to 24 weeks (OR 1.4, 95% CI 1.0-2.0). But this represented just 3.3% more patients versus placebo, a numerically small difference “of questionable clinical significance,” noted agency staff.

At Friday’s meeting, panelists will weigh in on these issues and vote on whether the supporting evidence demonstrates that gefapixant provides a clinically meaningful benefit for this patient population. While the FDA typically follows the advice of its advisory committees, it is not required to do so.

Mortality Reaches 20% for Hospitalized Patients With High-Risk Pulmonary Embolism

Posted by zedie

Worst outcomes for patients with hemodynamic collapse

A computer rendering of a thrombus in a blood vessel.

Mortality rates were high among patients with high-risk pulmonary embolism (PE), with the worst outcomes in those with hemodynamic collapse, according to a retrospective analysis of the Pulmonary Embolism Response Team (PERT) Consortium Registry.

In nearly 5,800 patients, in-hospital mortality occurred over five times more frequently among those with high-risk PE compared with those with intermediate-risk PE (20.6% vs 3.7%, P<0.001), reported Jay Giri, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and co-authors.

Similarly, the risk for major bleeding was also higher among high-risk PE patients versus intermediate-risk PE patients (10.5% vs 3.5%, P<0.001), they noted in the Journal of the American College of Cardiologyopens in a new tab or window.

“In comparison with previous data reported in high-risk PE patients, several patterns emerge,” Giri and team wrote. “First, our work confirms that high-risk PE patients are the predominant driver of observed short-term mortality in hospitalized PE patients.”

“While prior observational studies of high-risk PE patients have demonstrated short-term mortality ranging from 30% to 50%, our study demonstrated a somewhat lower overall mortality rate of 20.6% in all high-risk patients,” they continued. “This could be due to more complete capture of the entire high-risk spectrum in this registry, technological improvements in PE care, and/or improved care delivery methods in experienced PERT centers.”

In an editorial commentopens in a new tab or window, Behnam N. Tehrani, MD, of Inova Schar Heart and Vascular in Falls Church, Virginia, and co-authors noted that PE remains one of the top causes of cardiovascular death in the U.S., but more research is needed to improve risk assessment models.

The findings from this study “should serve as an impetus for universally accepted definitions for high-risk PE and the pursuit of novel metrics to elucidate signals of efficacy, including durable changes in hemodynamics, metabolic measures of tissue perfusion, and echocardiographic and proteomic-based predictors of survival and myocardial recovery,” they wrote.

In the study, multivariable regression analysis showed that there were a number of factors associated with in-hospital mortality:

Vasopressor use: OR 4.56, 95% CI 3.27-6.38, P<0.01
Extracorporeal membrane oxygenation (ECMO) use: OR 2.86, 95% CI 1.12-7.30, P=0.03
Identified clot-in-transit: OR 2.26, 95% CI 1.13-4.52, P=0.02
Malignancy: OR 1.70, 95% CI 1.13-2.56, P=0.01

Giri and colleagues also found that patients presenting with catastrophic PE had greater in-hospital mortality than their non-catastrophic counterparts (42.1% vs 17.2%, P<0.001), and ECMO (13.3% vs 4.8%, P<0.001) and systemic thrombolysis (25% vs 11.3%, P<0.001) were used more commonly in catastrophic PE.

Data for this study were taken from the PERT Consortium Registry, which includes patients from all 35 active U.S. registry sites admitted from Oct. 16, 2015 to April 8, 2022. Of the 5,790 patients in the study, 1,442 presented with high-risk PE and 2,976 presented with intermediate-risk PE.

Approximately half of the patients were men, and the average patient age was 63 years. Over half of the patients in both the high- and intermediate-risk cohorts were white.

High-risk PE patients were defined as those who, on initial hospital presentation, experienced hemodynamic collapse, hypotension, sustained systolic blood pressures <90 mm Hg, or the need for vasopressor support. Catastrophic patients additionally needed to have hemodynamic collapse that ultimately necessitated use of high-dose vasopressors due to concerns for impending cardiac arrest or those experiencing cardiac arrest with or without cardiopulmonary resuscitative efforts.

Intermediate-risk patients were defined as having systolic blood pressures >90 mm Hg, as well as evidence of right ventricular strain and/or biomarker abnormalities.

Giri and team noted that use of the PERT Consortium Registry may have excluded patients admitted to the hospital for PE who did not have previous consultations associated with the registry. Other potential limitations to the study included the fact that patients in the registry may have spent less time in the intensive care unit and may have had a shorter length of stay due to utilization of advanced therapies.

Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis – The Lancet Respiratory Medicine

Posted by zedie

Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis – The Lancet Respiratory Medicine https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00059-5/fulltext

SARS-CoV-2 can damage heart blood vessels without infecting them.

Posted by zedie

SARS-CoV-2 can damage heart blood vessels without infecting them: Study – Coronavirus Outbreak News https://www.indiatoday.in/coronavirus-outbreak/story/sars-cov-2-can-damage-heart-blood-vessels-without-infecting-them-study-1916430-2022-02-22?utm_source=fb_IA&utm_medium=cpc&utm_campaign=Feb22&fbclid=IwAR1GogzjX4eESgqHr2t_K3K1vGkz3Ll2qpyrHJncgBxaevKSofVcq-9aWfA

	zedie on Your Very Own Consciousness Ca…
	Cosmic Consciousness… on Your Very Own Consciousness Ca…
	zedie on New Research Links Reused Deep…
	The Healthiest Kinds… on The Healthiest Kinds of Salt:…
	zedie on Bobby Caldwell: Death from Flu…
	Diane Hardy on Bobby Caldwell: Death from Flu…
	zedie on So Is Coffee Bad for You in An…
	Americaoncoffee on So Is Coffee Bad for You in An…
	A Star on the Forehe… on How Often Should You Really…
	Get Hitch on Regain Control of Your Data in…

ARYAN'S BLOG

From Beyond The Rainbow Somewhere

covid19

Fifth Dose of COVID Vaccine Fails to Boost

Fifth Dose Fails to Strengthen Cell Immunity

Importance of Cellular Immunity

Interferon: A Powerful Antiviral Weapon