Category: Corona Virus Vaccine

Updated CDC recommendations address the prevention of respiratory viruses, emphasizing vaccines, hygiene, and air quality. The guidance is tailored to the current COVID-19 context and aims to protect vulnerable groups. Credit: James Gathany, Centers for Disease Control and Prevention

The CDC has issued new guidance for combating respiratory viruses, highlighting vaccination, hygiene, and air quality improvements. It focuses on reducing the spread of illnesses and protecting high-risk populations, adapting to the evolving COVID-19 situation.

On March 1, the CDC released updated recommendations for how people can protect themselves and their communities from respiratory viruses, including COVID-19. The new guidance brings a unified approach to addressing risks from a range of common respiratory viral illnesses, such as COVID-19, flu, and RSV, which can cause significant health impacts and strain on hospitals and healthcare workers. CDC is making updates to the recommendations now because the U.S. is seeing far fewer hospitalizations and deaths associated with COVID-19 and because we have more tools than ever to combat flu, COVID, and RSV.

Todays announcement reflects the progress we have made in protecting against severe illness from COVID-19, said CDC Director Dr. Mandy Cohen. However, we still must use the commonsense solutions we know work to protect ourselves and others from serious illness from respiratory virusesthis includes vaccination, treatment, and staying home when we get sick.

As part of the guidance, CDC provides active recommendations on core prevention steps and strategies:

When people get sick with a respiratory virus, the updated guidance recommends that they stay home and away from others. For people with COVID-19 and influenza, treatment is available and can lessen symptoms and lower the risk of severe illness. The recommendations suggest returning to normal activities when, for at least 24 hours, symptoms are improving overall, and if a fever was present, it has been gone without use of a fever-reducing medication.

Once people resume normal activities, they are encouraged to take additional prevention strategies for the next 5 days to curb disease spread, such as taking more steps for cleaner air, enhancing hygiene practices, wearing a well-fitting mask, keeping a distance from others, and/or getting tested for respiratory viruses. Enhanced precautions are especially important to protect those most at risk for severe illness, including those over 65 and people with weakened immune systems. CDCs updated guidance reflects how the circumstances around COVID-19 in particular have changed. While it remains a threat, today it is far less likely to cause severe illness because of widespread immunity and improved tools to prevent and treat the disease. Importantly, states and countries that have already adjusted recommended isolation times have not seen increased hospitalizations or deaths related to COVID-19.

While every respiratory virus does not act the same, adopting a unified approach to limiting disease spread makes recommendations easier to follow and thus more likely to be adopted and does not rely on individuals to test for illness, a practice that data indicates is uneven.

The bottom line is that when people follow these actionable recommendations to avoid getting sick, and to protect themselves and others if they do get sick, it will help limit the spread of respiratory viruses, and that will mean fewer people who experience severe illness, National Center for Immunization and Respiratory Diseases Director Dr. Demetre Daskalakis said. That includes taking enhanced precautions that can help protect people who are at higher risk for getting seriously ill.

The updated guidance also includes specific sections with additional considerations for people who are at higher risk of severe illness from respiratory viruses, including people who are immunocompromised, people with disabilities, people who are or were recently pregnant, young children, and older adults. Respiratory viruses remain a public health threat. CDC will continue to focus efforts on ensuring the public has the information and tools to lower their risk or respiratory illness by protecting themselves, their families, and their communities.

This updated guidance is intended for community settings. There are no changes to respiratory virus guidance for healthcare settings.

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COVID-19, Flu, and RSV: CDC Updates and Simplifies Respiratory Virus Recommendations - SciTechDaily

Scientists in Germany were baffled after a 62-year-old man from Magdeburg claimed that he received more than 200 vaccine doses for Covid-19. Researchers at Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU) and Universittsklinikum Erlangen found about the man from newspaper reports and studied his immune response.

"We learned about his case via newspaper articles. We then contacted him and invited him to undergo various tests in Erlangen. He was very interested in doing so," said Dr Kilian Schober from the Institute of Microbiology Clinical Microbiology, Immunology and Hygiene in a press release. The release also stated, that the man from Germany received 217 vaccinations deliberately and for private reasons within 29 months.(Also Read: CDC shortens isolation time for COVID-19 patients in new guidelines)

"The individual has undergone various blood tests over recent years," explained Schober. "He gave us his permission to assess the results of these analyses. In some cases, samples had been frozen, and we were able to investigate these ourselves. We were also able to take blood samples ourselves when the man received a further vaccination during the study at his own insistence. We were able to use these samples to determine exactly how the immune system reacts to the vaccination."

According to the press release, the test subject had a high number of T-effector cells that can defend the body against Covid-19 infection. When compared to a control group of individuals who received three immunisations, the test subject had more T-effector cells. Furthermore, the researchers found that these effector cells were not fatigued and were similarly effective as those in the control group who had received the normal number of vaccinations. (Also Read: All about two rare Covid-19 vaccine side effects detected in a study)

"The number of memory cells was just as high in our test case as in the control group. Overall, we did not find any indication for a weaker immune response; rather, it was the contrary," explains Katharina Kocher, one of the leading authors of the study published in Lancet Infectious Diseases journal.

Additional testing revealed the man's immune system's ability to fight off other infections remained unchanged. Therefore, it appears that the immune system was 'not damaged' by overvaccination.

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German man claims to receive 217 Covid-19 vaccine doses, shocks researchers - Hindustan Times

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.

In the early days of the pandemic, before we really understood what COVID was, two specialties in the hospital had a foreboding sense that something was very strange about this virus. The first was the pulmonologists, who noticed the striking levels of hypoxemia low oxygen in the blood and the rapidity with which patients who had previously been stable would crash in the intensive care unit.

The second, and I mark myself among this group, were the nephrologists. The dialysis machines stopped working right. I remember rounding on patients in the hospital who were on dialysis for kidney failure in the setting of severe COVID infection and seeing clots forming on the dialysis filters. Some patients could barely get in a full treatment because the filters would clog so quickly.

We knew it was worse than flu because of the mortality rates, but these oddities made us realize that it was different too not just a particularly nasty respiratory virus but one that had effects on the body that we hadn't really seen before.

That's why I've always been interested in studies that compare what happens to patients after COVID infection vs what happens to patients after other respiratory infections. This week, we'll look at an intriguing study that suggests that COVID may lead to autoimmune diseases like rheumatoid arthritis, lupus, and vasculitis.

The study appears in the Annals of Internal Medicine and is made possible by the universal electronic health record systems of South Korea and Japan, who collaborated to create a truly staggering cohort of more than 20 million individuals living in those countries from 2020 to 2021.

The exposure of interest? COVID infection, experienced by just under 5% of that cohort over the study period. (Remember, there was a time when COVID infections were relatively controlled, particularly in some countries.)

The researchers wanted to compare the risk for autoimmune disease among COVID-infected individuals against two control groups. The first control group was the general population. This is interesting but a difficult analysis, because people who become infected with COVID might be very different from the general population. The second control group was people infected with influenza. I like this a lot better; the risk factors for COVID and influenza are quite similar, and the fact that this group was diagnosed with flu means at least that they are getting medical care and are sort of "in the system," so to speak.

But it's not enough to simply identify these folks and see who ends up with more autoimmune disease. The authors used propensity score matching to pair individuals infected with COVID with individuals from the control groups who were very similar to them. I've talked about this strategy before, but the basic idea is that you build a model predicting the likelihood of infection with COVID, based on a slew of factors and the slew these authors used is pretty big, as shown below and then stick people with similar risk for COVID together, with one member of the pair having had COVID and the other having eluded it (at least for the study period).

After this statistical balancing, the authors looked at the risk for a variety of autoimmune diseases.

Compared with those infected with flu, those infected with COVID were more likely to be diagnosed with any autoimmune condition, connective tissue disease, and, in Japan at least, inflammatory arthritis.

The authors acknowledge that being diagnosed with a disease might not be the same as actually having the disease, so in another analysis they looked only at people who received treatment for the autoimmune conditions, and the signals were even stronger in that group.

This risk seemed to be highest in the 6 months following the COVID infection, which makes sense biologically if we think that the infection is somehow screwing up the immune system.

And the risk was similar with both COVID variants circulating at the time of the study.

The only factor that reduced the risk? You guessed it: vaccination. This is a particularly interesting finding because the exposure cohort was defined by having been infected with COVID. Therefore, the mechanism of protection is not prevention of infection; it's something else. Perhaps vaccination helps to get the immune system in a state to respond to COVID infection more appropriately?

Yes, this study is observational. We can't draw causal conclusions here. But it does reinforce my long-held belief that COVID is a weird virus, one with effects that are different from the respiratory viruses we are used to. I can't say for certain whether COVID causes immune system dysfunction that puts someone at risk for autoimmunity not from this study. But I can say it wouldn't surprise me.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn't, is available now.

Credits: Image 1: Centers for Disease Control and Prevention Image 2: Worldometer Image 3: Annals of Internal Medicine Image 4: F. Perry Wilson, MD, MSCE Image 5: F. Perry Wilson, MD, MSCE Image 6: F. Perry Wilson, MD, MSCE Image 7: F. Perry Wilson, MD, MSCE Image 8: F. Perry Wilson, MD, MSCE

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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: SARS CoV-2 Is a Very Weird Virus-Medscape-Mar04,2024.

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SARS CoV-2 Is a Very Weird Virus - Medscape

A German man who claimed to have received more than 200 COVID-19 vaccinations has shown no signs of immunity fatigue.

In research published in The Lancet Infectious Diseases, scientists from German and Austrian universities put the mans immune system under the microscope after discovering the case from a series of newspaper reports.

According to the researchers, the 62-year-old from Magdeburg in Germany claimed to have received 217 vaccinations against SARS-CoV-2 the virus that causes COVID-19 within 3 years. They confirmed at least 134 vaccinations took place.

While the reasons for these vaccines were not described in the study, news reports in 2022 allege a then 60-year-old man from the same town received almost 100 shots to sell forged vaccination cards. These included eight different vaccine types, including mRNA-based jabs.

We [then] contacted him and invited him to undergo various tests in Erlangen. He was very interested in doing so, says Kilian Schober, a joint-senior author of the study.

This investigation into the effects of hypervaccination saw blood and saliva samples from the man (known as HIM), studied by groups from three universities.

Some scientists believed over-exposure to the same vaccination could fatigue the immune system, as is known to be the case with other infectious diseases like HIV and Hepatitis.

But in HIMs case, it appears more than 100 COVID jabs have had little negative effect. Memory cells present in his samples were as high as in control groups used for the study, and there appeared no evidence of a weakened immune system, according to the researchers.

Though HIMs samples showed no sign of the man having ever been infected with the virus, its unclear whether this is due to his hypervaccination status.

The team says there is no overall positive benefit being identified in his case.

The observation that no noticeable side effects were triggered despite this extraordinary hypervaccination indicates that the drugs have a good degree of tolerability, says Schober.

However, the researchers stress that current advice in many jurisdictions for a two or three-dose vaccination protocol followed by periodic boosters is appropriate, noting they do not endorse hypervaccination as a strategy to enhance adaptive immunity.

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A German man got over 100 COVID jabs in 3 years. Did his immunity hold up? - Cosmos

A man in Germany who chose to have 217 Covid-19 vaccinations has become a focal point for research into the effects of excessive immunisation on the human body.

The unique case has offered insights into the resilience and adaptability of the immune system when subjected to repeated vaccine doses.

The man went far beyond conventional medical advice, pushing the boundaries of what is known about vaccine tolerance and immune response. Researchers did not reveal how he was able to gain access to so many vaccine shots.

There is official evidence of the 62-year-old man having 134 Covid-19 vaccines of eight different types over a nine month period, although he claims the amount to be 217 in total over 29 months. The majority of the over 60 million people in Germany adhered to the standard protocol of receiving just three shots.

We became aware of this case via newspaper reports back in 2022, Dr Kilian Schober from the Institute of Microbiology Clinical Microbiology, Immunology, and Hygiene at Friedrich-Alexander-Universitat Erlangen-Nurnberg told The National.

For us it was clear that this represented a unique chance to investigate the consequences of hypervaccination on the human immune system, he said.

This initial spark of interest led them to extend an invitation to the man who lives in Magdeburg for a series of tests. He was very interested in doing so, Dr Schober added.

The scientific community had previously speculated on the potential consequences of what has been termed 'hypervaccination'.

Concerns were raised that excessive exposure to vaccine antigens might induce a state of fatigue in immune cells, potentially compromising their ability to respond effectively to pathogens.

The researchers embarked on a comprehensive analysis of his immune response, utilising blood samples collected over several years.

Not only did his immune system remain fully functional, but certain immune cells and antibodies against SARS-CoV-2 were present in considerably higher concentrations than observed in people who had received a standard three-dose vaccination regimen.

The results were published in the journal The Lancet Infectious Diseases.

The study revealed that the man's T-effector cells, vital components of the immune system's arsenal against viruses, were abundant and potent.

The test person even had more of these compared to the control group of people who have received three vaccinations, Katharina Kocher, one of the leading authors of the study, said.

Additionally, the researchers found no indication of a diminished immune response. On the contrary, the immune system's performance was exemplary, with memory T cells, which can develop into effector cells as needed, present in healthy numbers.

There was also a significant increase in antibodies against SARS-CoV-2 following his 217th vaccination, indicating that his immune system continued to respond vigorously to each new vaccine dose.

High levels of antibodies and T cells could be expected after hypervaccination, Dr Schober said.

Of note, the quality was not affected, indicating that hypervaccination did not have a strong positive or negative impact on the immune system. In a way, this points to the robustness of our immune system.

The comprehensive investigation also extended to the immune system's capacity to combat other pathogens, with tests indicating no compromise in its overall effectiveness.

Our test case was vaccinated with a total of eight different vaccines, including different available mRNA vaccines, Dr Schober said, highlighting the broad spectrum of vaccines administered without triggering noticeable side effects.

This aspect of the study underscores the vaccines' tolerability and the immune system's adaptability to various vaccine formulations.

However, the researchers cautioned against generalising the findings from this singular case to the wider population.

He did not experience any side effects. However, it must be stressed that this is a single case and generalisability to a larger group of people is questionable, Dr Schober said.

Current research indicates that a three-dose vaccination, coupled with regular top-up vaccines for vulnerable groups, remains the favoured approach. There is no indication that more vaccines are required, he clarified.

Updated: March 05, 2024, 4:42 PM

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Man in Germany receives 217 Covid-19 vaccines - The National

A Public Health Detailing campaign focused on building confidence in and access to the COVID-19 vaccines was a key part of reducing racial inequities in COVID-19 vaccination rates across New York City.

In the spring of 2021, significant racial inequities in COVID-19 vaccination rates in New York City (NYC) emerged, owing to a history of community disinvestment and structural racism. To address these inequities, the New York City Department of Health (DOHMH) undertook a multi-pronged, community place-based strategy[1] to build confidence in and ensure equitable access to COVID-19 vaccines. In our latest publication, Using Public Health Detailing to Increase Access and Confidence in COVID-19 Vaccines and Reinvest in Disproportionately Impacted NYC Communities we describe one part of this strategy in-depth.

Public Health Detailing (PHD) is a provider education and outreach program based off of the pharmaceutical detailing model.[2] As part of the program, DOHMH outreach representatives (reps) make in-person visits to healthcare providers offices to promote specific public health recommendations and offer resources to assist in the implementation of these recommendations. The PHD program operates out of DOHMH and has been used in recent years as a strategy to address a host of public health challenges. Building upon this existing infrastructure, DOHMH rapidly stood up an emergency detailing campaign to help better equip primary care providers to promote COVID-19 vaccination and improve access to vaccination by sharing information with practices seeking to become vaccination sites.

With a close eye on racial inequities in vaccination rates, the PHD team used hyperlocal vaccination data and an equity framework in the selection of its priority neighborhoods for this campaign, focusing initially on selected sections of the Bronx and Brooklyn that were disproportionately impacted by COVID-19 as defined by the NYC Taskforce on Racial Inclusion and Equity. The campaign later expanded to include parts of all five NYC boroughs, with an emphasis on neighborhoods with a large Black population and low vaccination rates.

PHD staff were quickly deployed to train a team of outreach reps in the detailing approach and COVID-19 disease and vaccine content. Importantly, the assigned reps were recruited from the Citys contact tracing program, Test and Trace; these reps came from diverse NYC communities and generally spoke at least one additional language, making them credible messengers in historically marginalized communities. Following a brief training, reps conducted outreach visits to primary care practices to share a series of key recommendations that promoted vaccination and the importance of bi-directional patient and provider communication.

To assist providers in having conversations with their patients and educating patients on the safety, efficacy, and need for vaccination, reps offered a suite of DOHMH resources, including provider communication guides and patient education materials. In addition to sharing these key messages, another important role for the outreach reps was to serve as a feedback loop for DOHMH leadership with respect to community providers. Information obtained about challenges on the ground was shared with DOHMH leadership regularly and fed back into the agencys emergency response.

Our team conducted 2873 detailing sessions at 1281 sites from May 2021 to March 2022. Over time, we found that patient barriers to vaccination were consistent and focused primarily on a lack of trust in the vaccine development process, concerns around vaccine safety, and a lack of perceived need for the vaccine. In contrast, provider barriers to offering vaccination changed over time, first focusing on the lack of appropriate equipment for storage and handling of the vaccine and later to a preference for referring patients out. A number of interesting trends were also verbally reported to reps including, for example, a handful of providers arguing without supporting data that immunity achieved via infection was more robust than vaccine-acquired immunity.

Purposefully, this campaign was conducted in neighborhoods where other community engagement activities were occurring. Thus, it is not possible to quantify the impact of PHD alone; however, by the time the campaign concluded, neighborhoods that were identified as being disproportionately impacted by COVID-19 showed almost no disparities in vaccination rates compared with neighborhoods that were less impacted.1

Lastly, by reinvesting in historically disadvantaged communities and working with trustworthy messengers to provide resources and support to primary care providers when they were very much needed, PHD also helped to build relationships between DOHMH and community-based providers, some of whom may not have been formally engaged with public health agencies. These connections are particularly important as they may outlast the current campaign, help address COVID-19 recovery, and potentially help prepare for future emergencies. These factors make the program an important piece of a larger community outreach initiative and, coupled with the programs flexibility, one that is easily adaptable by other public health departments. To learn more, please check out our full publication, available here.

[1] Ige O, Watkins J, Pham-Singer H, Dresser M, Maru D, Morse M. Embedding health equity in a public health emergency response: New York Citys COVID-19 vaccination experience. NEJM Catalyst. 2023;4(2):114.

[2] Larson K, Levy J, Rome MG, Matte TD, Silver LD, Frieden TR. Public Health Detailing: a strategy to improve the delivery of clinical preventive services in New York City. Public Health Rep. 2006;121(3):228234.

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Public Health Detailing as a Tool for Increasing COVID-19 Vaccine Confidence and Access and Addressing Racial Inequities - JPHMP Direct

Thanks for joining us today and for your questions -- far more than we were able to address in a short space of time.

We hope youve found this discussion useful -- Covid-19 remains a controversial topic, but Michelle and I and the rest of Bloombergs healthcare team are using a data, fact-led approach.

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Live: How Does Covid Affect Your Heart? Are Vaccines Safe? Questions Answered - Bloomberg

Laura Santhanam:

You know, we've been dealing with misinformation for quite some time when it comes to vaccines. You know, it starting in in the late 1990s, with thinking about the measles, mumps rubella vaccine, and to this day, there are still people who, you know, withhold that vaccine from their children, because they think it might cause problems that just evidence studies conducted over so many years in so many countries. Just it they continue to debunk that since retracted study.

But that sort of laid the groundwork for some of the misinformation campaigns we're seeing about COVID vaccine now, whether it's talking about how quickly it was deployed, and then, you know, when politics are getting involved in some of those campaigns, it makes it a message disentangle.

Time and again, when I've been talking to clinicians about this, they recommend that people ask their doctors, if you have questions about the COVID vaccine, measles vaccine, any of these vaccines that are recommended that are approved and vetted by the CDC, by the FDA, you know, have those conversations with your doctors.

But also, you know, perhaps equally importantly, doctors should be ready to have those conversations with their patients. I had a conversation with a doctor in South Alabama who was saying, you know, physicians should be welcoming these conversations. They should be ready to answer questions, and shouldn't discourage patients from having them in the first place.

Vaccine misinformation expert also told me that people are going to misinformation for a number of reasons. But some of those reasons is because they weren't able to get answers when they needed them from their health care providers in the first place. So it just be ready to have these conversations and welcome them.

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How vaccine hesitancy is contributing to rising rates of measles and COVID - PBS NewsHour

Anti-RBD IgG titers and plasma neutralizing activity induced by COVID-19 mRNA vaccination in HDs and LTRs

We enrolled 44 HDs and 54 LTRs to comprehensively evaluate mRNA vaccine-induced antibodies and cellular immune responses (Table1). The mRNA vaccines, Pfizer BNT162b2 or Moderna mRNA-1273 were investigated. Blood samples were obtained at five-time points: before vaccination, 1, 3, and 6 months after the second vaccination, and 1 month after the third vaccination (Fig.1a).

a Schematic overview of the cohort. b Anti-RBD IgG endpoint titers in HDs (black) and LTRs (red) (sample size, pre: 25 vs 12, 1m after 2nd: 25 vs 54, 3m after 2nd: 24 vs 53, 6m after 2nd: 44 vs 54, 1m after 3rd: 44 vs 51). c Multivariable logistic regression model (OR and 95% CI) for predictors of weak and strong responders (lower and higher than median antibody titer in HDs at 1 month after third vaccination, respectively). d Anti-RBD antibody titers in HDs (black), LTRs taking only a calcineurin inhibitor (CNI group, red) and LTRs taking CNI and other medications (CNI+other drug(s) group, blue) (sample size, pre: 25 vs 1 vs 11, 1m after 2nd: 25 vs 20 vs 27, 3m after 2nd: 25 vs 23 vs 30, 6m after 2nd: 44 vs 23 vs 31, 1m after 3rd: 44 vs 21 vs 29). e Anti-RBD IgG endpoint titers in HDs 1 month after 2nd vaccination (black) and in CNI+other drug(s) group 1 month after 3rd vaccination (blue) (sample size, 25 vs 29). f Fold-induction in anti-RBD IgG endpoint titers after third vaccination (HDs: black, CNI: red, CNI+other drug(s): blue). Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders. (sample size, 44 vs 21 vs 29). g pVNT50 against SARS-CoV-2 Wuhan-1 (HDs: black, CNI: red, CNI+other drug(s): blue). h pVNT50 in HDs 1 month after 2nd vaccination (black) and in CNI+other drug(s) group 1 month after 3rd vaccination (blue) (sample size, 25 vs 29). i Fold-induction in pVNT50 after third vaccination. Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders (HDs: black, CNI: red, CNI+other drug(s): blue) (sample size, 44 vs 21 vs 29). P values (two-sided) were calculated using the MannWhitney U-test. All experiments were performed once. Error bars indicate the interquartile range.

All LTRs were administered CNIs, such as tacrolimus or cyclosporine. Some LTRs took additional medications, such as the metabolic antagonist MMF, a steroid, or the mTOR inhibitor everolimus. Specifically, 23, 12, 2, 11, 5, and 1 LTRs had taken only a CNI; CNI and MMF; CNI and everolimus; CNI and a steroid; CNI, MMF, and a steroid; and CNI, everolimus, and a steroid, respectively. Seven LTRs received entecavir, a drug used to treat hepatitis B, and immunosuppressive therapy.

Anti-RBD antibody titers in LTRs were significantly lower than those in HDs at all time points (Fig.1b) (p<0.0001 at 1 and 3 months, p=0.0005 at 6 months after the second vaccination, p=0.0002 after the third vaccination). Anti-RBD antibody titers in all HDs exceeded the WHO standard (dashed line, 1000U/mL); however, 53.2% of LTRs had anti-RBD antibody titers below the WHO standard at 1 month after the second vaccination. However, anti-RBD antibody titers in 92.2% of the LTRs after the third vaccination exceeded the WHO standard, suggesting that effective immune responses can be achieved in immunosuppressed LTRs by the third vaccination.

Interestingly, the variability in antibody levels among LTRs was wide compared with that in HDs. Therefore, we aimed to identify the factors that affect the variability in antibody production in LTRs. LTRs that obtained anti-RBD antibody levels higher and lower than the median value of antibody titers in HDs after the third vaccination were categorized as strong and weak responders, respectively. We conducted a multiple logistic regression analysis with clinical parameters (Fig.1c), suggesting that taking multiple drugs decreased antibody levels (p=0.0048, OR=0.0285).

We regrouped LTRs for comparison between LTRs taking only a CNI and taking a CNI and more drugs (CNI+other drug(s)) (Fig.1d). There was no difference in the antibody titers between the CNI group and HDs after the third vaccination. Contrarily, antibody titers were significantly lower in the CNI+other drug(s) group than in the HDs and the CNI group (p<0.0001 among HDs vs. CNI+other drug(s), p<0.0001 among CNI vs. CNI+other drug(s)). However, the anti-RBD antibody titers after the third vaccination in the CNI+other drug(s) group were the same as those in HDs 1 month after the second vaccination (Fig.1e; p=0.3255). After the second vaccination, anti-RBD antibodies in plasma were induced in 49 of 54 LTRs. The 5 LTRs in whom anti-RBD antibodies were not induced after the second vaccination all showed induction of the antibodies after the third vaccination. However, there was one individual who, despite having a positive plasma anti-RBD antibody titer after the second dose, did not benefit from the third booster dose and tested negative. This individual was taking three medications, namely CNI, MMF, and steroids (5mg/day), and had a low anti-RBD antibody titer even after the second vaccination.

Additionally, LTRs were regrouped based on clinical information apart from medication (Supplementary Fig.1). Antibody titers were considerably lower in deceased donor liver transplant (DDLT) than in living-donor liver transplant (LDLT) (Supplementary Fig.1a). Furthermore, antibody titers in LTRs less than 12 years after transplantation were lower (Supplementary Fig.1b). LTRs who experienced rejection reactions after transplantation also exhibited lower antibody titers than those who did not (Supplementary Fig.1c). LTRs who have taken MMF also exhibited lower antibody titers than those who have not (Supplementary Fig.1d). These factors are related to the regimen of immunosuppressive drugs, and the multivariate analysis suggested that the number of drugs has the most significant impact. Noteworthily, antibody titers of 89.7% in the CNI+other drug(s) group were increased by the third vaccination, and the fold induction of antibody titers in the CNI+other drug(s) group was similar to that in HDs (Fig.1f; p=0.7666).

Next, we measured the changes in the neutralizing activity of plasma from HDs and LTRs (Fig.1g). Neutralizing activity in most of the CNI+other drug(s) was below the detection limit after the second vaccination, and was significantly lower than that in HDs after the third vaccination (p=0.0001). Contrarily, the neutralizing activity in the CNI+other drug(s) group after the third vaccination was similar to that in HDs one month after the second vaccination (Fig.1h; p=0.2985). Furthermore, although the fold-induction of neutralizing activity in CNI+other drug(s) by the third vaccination was significantly lower than that of HDs, 82.8% of the CNI+other drug(s) group got a booster effect (Fig.1i) (p=0.0006 among HDs vs. CNI+other drug(s)). These results suggest that the third doses of mRNA vaccine are worthwhile for the induction of neutralizing activity in LTRs, but may not be sufficient compared to HDs.

Generally, immunosuppressive drugs, including CNIs, contribute to the suppression of T-cell responses. To investigate whether the reduction in antibody titers in LTRs is affected by changes in CD4 helper T-cell function, we performed flow cytometry analysis to evaluate the CD4+ T-cell responses. The frequency of total SARS-CoV-2 spike-specific CD4+ Tcells was measured using CD154 as an activation marker (Supplementary Fig.2a). The frequency of spike-specific CD4+ Tcells in CNI+other drug(s) at 1, 3, and 6 months after the second vaccination was significantly lower compared to HDs (Fig.2a; p=0.0117, p=0.0208, and p=0.0047 at 1, 3, and 6 months after the second vaccination, respectively). There was no significant difference between HDs and the CNI group at 1 month (p>0.9999), 3 months (p=0.6506), and 6 months (p=0.1379) after the second vaccination. Moreover, there were significant differences between the CNI and CNI+other drug(s) groups 3 months (p=0.024), and 6 months (p=0.0051) after the second vaccination (Fig.2a). However, there is no significant difference among HDs, the CNI group, and the CNI+other drug(s) group after the third vaccination. Regardless of HDs or LTRs, spike-specific CD4+ Tcells decreased over time after the second mRNA vaccination (Supplementary Fig.2b).

Frequency of spike-specific CD154+ (a), Th1 (b), and Th2 (c) CD4+ Tcells in total memory Tcells from HDs (black), CNI group (red), and CNI+other drug(s) group (blue). df Fold-induction of spike-specific CD154+, Th1, and Th2 CD4+ Tcells by the third vaccination. Pie charts represent the proportion of individuals with fold-induction higher than 1, and gray slice shows frequency of negative responders. (HDs: black, CNI: red, CNI+other drug(s): blue). g The ratio of spike-specific Th1 to Th2 CD4+ Tcells (HDs: black, CNI: red, CNI+other drug(s): blue). P values (two-sided) in (a) to (g) were calculated using the Mann-Whitney U-test. h Correlation matrix of antibody and CD4+ T-cell responses in HDs and LTRs. Shades of blue represent positive correlations approaching 1, while shades of red denote negative correlations nearing -1. P values (two-sided) were calculated using the Spearmans rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.

Next, we measured the cytokine profiles of the total spike-specific CD4+ Tcells (Fig.2b, c, Supplementary Fig.2a). The frequency of Th1 cells in CNI+other drug(s) after the second vaccination was significantly lower compared to HDs (Fig.2b). On the contrary, the frequency of Th2 cells was higher in the CNI group than in HDs (Fig.2c). The frequency of total CD154+ spike-specific CD4+ Tcells and Th1 cells increased by the third mRNA vaccination in HDs and LTRs, and there was no significant difference between HDs and LTRs after the third vaccination (Fig.2a, b).

We next examined the effect of the third booster on memory CD4+ T cell responses by calculating the fold-induction of CD154+, Th1, and Th2 cell frequencies. We observed a boost effect in ~75% of individuals for CD154+ and Th1 cells in all groups, and in ~50% of individuals for Th2 cells (Fig.2df). Furthermore, Th1/Th2 ratio in LTRs was significantly lower compared to HDs (Fig.2g), suggesting that LTRs are more susceptible to the induction of Th2-biased CD4+ T-cell responses.

We next evaluated the correlation between CD4+ T-cell and antibody responses. One month after the second vaccination, the frequency of CD154+CD4+ T and Th1 cells was positively correlated with anti-RBD antibody titers in HDs and LTRs (Fig.2h). Moreover, CD4+ T-cell frequency before the third vaccination positively correlated with antibody titers after the third vaccination (HDs: r=0.299, p=0.049 for CD154+CD4+ Tcells vs. anti-RBD IgG; LTRs: r=0.483, p=0.0004 for CD154+CD4+ Tcells vs. anti-RBD IgG; r=0.433, p=0.0019 for Th1 CD4 Tcells vs. anti-RBD IgG). These results suggest that long-term CD4+ T-cell responses after the second vaccination contribute to the booster effect on antibody levels after the third vaccination.

In addition to antibodies and CD4+ Tcells, CD8+ T-cell responses also contribute to defense against SARS-CoV-2 infection22,23. However, COVID-19 mRNA vaccines reportedly have a lower ability to induce CD8+ Tcells than CD4+ Tcells24. Moreover, few reports demonstrate CD8+ T-cell responses to mRNA vaccines in LTRs. Therefore, we investigated whether spike-specific CD8+ Tcells were induced in LTRs and compared their frequency with HDs. We defined 4-1BB+CD69+CD8+ Tcells as spike-specific CD8+ Tcells in the PBMCs stimulated with spike peptides (Supplementary Fig.3a). Spike-specific CD8+ Tcells were detected in 100% of HDs and 93% of LTRs 1 month after the second vaccination (Fig.3a). However, the frequency of spike-specific CD8+ Tcells by the third vaccination did not increase in most HDs and LTRs (Fig.3b, HDs 55.8%, CNI 55%, and CNI+other drug(s) 42.9%). Compared to HDs, the frequency of LTRs was significantly lower at all time points, regardless of taking single or multiple drugs (Fig.3a). Furthermore, in contrast to antibody responses, there was no correlation between spike-specific CD8+ and CD4+ T cell responses (Fig.3c). These results suggest that the third boost effect on memory T-cell responses differs between CD4+ and CD8+ Tcells. We then checked the differentiation status of the spike-specific CD8+ T cells induced by vaccination using CD27, CD45RO, and CD57 markers to define central memory (CM; CD27+CD45RO+), effector memory (EM; CD27-CD57-), and effector (CD27-CD57+) subsets. As a result, the phenotypes of spike-specific CD8+ T cells were changed from CM to EM at 6 months after 2nd vaccination in both the HDs and LTRs who showed positive effects of boosting spike-specific CD8+ T-cell responses (Healthy boost+ and LTR boost+), although the phenotypes of total memory CD8+ T cells were not changed over time (Fig.3d, e). After 3rd mRNA vaccination, HDs and LTRs showed different phenotypes of spike-specific CD8+ T cells, with decreased CM and increased EM and Effector in HDs, but a trend toward increased CM in LTRs.

a Frequencies of spike-specific CD69+4-1BB+CD8+ Tcells in total memory Tcells from HDs (black), CNI group (red), and CNI+other drug(s) group (blue). b Fold-induction of spike-specific CD69+4-1BB+CD8+ Tcells after third vaccination. Pie charts represent the proportion of individuals with fold-induction > 1, and gray slice shows frequency of negative responders (HDs: black, CNI: red, CNI+other drug(s): blue). c Correlation matrix of CD4+ and CD8+ T-cell responses. Shades of blue represent positive correlations approaching 1, while shades of red denote negative correlations nearing -1. P values were calculated using the Spearmans rank test. Frequencies of CM, EM and effector within CD8+ total memory T cells (d) and spike-specific CD69+4-1BB+CD8+ Tcells (e) in individuals who did (boost+) or did not (boost-) receive boost effect from 3 doses of mRNA vaccine (HDs boost: gray, HDs boost+: black, LTRs boost: red, LTRs boost+: dark red). P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test compared to 1 month after 2nd vaccination. Frequency of spike-specific CD69+4-1BB+CD8+ Tcells expressing GZMA (f), GZMB (g), and Perforin (h) (HDs: black, CNI: red, CNI+other drug(s): blue). i Expression of multiple cytotoxic molecules in spike-specific CD69+4-1BB+CD8+ Tcells. Each colors arc length and pie charts area represent the expression of each cytotoxic molecule (GZMA: red, GZMB: blue, Perforin: green) and cells expressing the indicated number of cytotoxic molecules (0: yellow, 1: green, 2: blue, 3: red), respectively. P values (two-sided) in (a), (b), (f), (g), and (h) were calculated using the MannWhitney U-test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.

Furthermore, we previously reported that differences in the expression patterns of cytotoxic molecules could observe qualitative differences in mRNA vaccine-induced spike-specific CD8+ Tcells20. Therefore, we compared the expression of cytotoxic molecules in spike-specific CD8+ Tcells between HDs and LTRs. Supplementary Fig.3b shows the expression patterns of GZMA, GZMB, and Perforin, and gating. Regardless of HDs or LTRs, most spike-specific CD8+ Tcells expressed GZMA before and after the third vaccination (Fig.3f). The proportion of cells expressing GZMA in CNI+other drug(s) was significantly, but slightly, lower than that in HDs before the third vaccination (p=0.0237). However, the proportion of cells expressing GZMB and Perforin was not different between HDs and LTRs before and after the third boost (Fig.3g, h). Furthermore, the expression profiles of GZMA, GZMB, and Perforin were not significantly different between the groups (Supplementary Fig.4a, b). The proportion of subpopulations expressing GZMA, GZMB, and Perforin was approximately 20% in the spike-specific CD8+ Tcells of each group, and the proportion of subpopulations expressing only GZMA was over 50% (Fig.3i). However, we did not observe any qualitative differences in spike-specific CD8+ Tcells induced by the third boost.

HDs and LTRs were vaccinated with an mRNA vaccine based on the Wuhan-1 strain, and the induced antibodies potentially reduced the effectiveness against the recently emerged Omicron sublineages. Therefore, we measured the antibody titers before and after the third boost against RBD corresponding to the Omicron sublineages, and found that anti-RBD antibody titers before the third boost against all sublineages were significantly reduced compared to those against the Wuhan-1 (Fig.4a, b). Among sublineages, the anti-RBD antibody titers against BQ.1.1 and XBB were particularly reduced (HDs, 8.43-fold reduction; CNI, 5.23-fold reduction; CNI+other drug(s), 4.41-fold reduction against BQ.1.1, HDs, 11.9-fold reduction; CNI, 6.35-fold reduction; CNI+other drug(s), 4.41-fold reduction against XBB). Furthermore, the neutralizing activity before the third boost was below the detection limit for BA.5, BQ.1.1, and XBB in most individuals (Fig.4c). Furthermore, there was no change in the trend toward lower antibody titers for each Omicron sublineage (Fig.4d, e). In particular, the CNI+other drug(s) group showed significantly lower anti-RBD antibody levels against all sublineages than the HDs and CNI groups. Additionally, there was a slight improvement in neutralizing activity against the BA.5 strain, but not BQ.1.1 and XBB strains, by the third vaccination (Fig.4f).

a, d Anti-RBD antibody endpoint titers against indicated strains at (a) pre- and (d) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). Fold-change of anti-RBD IgG against variants of concern endpoint titers at (b) pre- and (e) post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of red indicate a decrease in antibody titers, with darker shades signifying a larger negative fold change. pVNT50 against strains at (c) pre- and (f) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). P values (two-sided) in (a), (c), (d), and (f) were calculated using the MannWhitney U-test. P values (two-sided) in (b) and (e) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, pre-3rd boost: 44 vs 23 vs 31, post-3rd boost: 44 vs 21 vs 30). All experiments were performed once. Error bars indicate the interquartile range.

Collectively, these results suggest that the third vaccination with the Wuhan-1 mRNA vaccine may not be sufficient to induce antibody responses against Omicron sublineages, particularly BQ.1.1 and XBB, in HDs and LTRs.

Finally, we investigated the differences in cellular immunity against Omicron sublineages between HDs and LTRs. The frequency of spike-specific CD154+CD4+ Tcells was evaluated in PBMCs before the third boost. There was no difference in response to the Wuhan-1 and mutant strains in all groups (Supplementary Fig.5a, b). The same trend was observed for spike-specific Th1 CD4+ Tcells (Fig.5a, b). However, the frequency of CD154+CD4+ Tcells and Th1 cells responding to mutant strains in HDs after the third boost was significantly and slightly lower than that of cells responding to Wuhan-1(Supplementary Fig.5c, d, Fig.5c, d). The same trend was observed in spike-specific Th2 CD4+ Tcells (Supplementary Fig.4eh). These results indicate that, unlike antibody responses, CD4+ T-cell responses induced by mRNA vaccines can react to Omicron sublineages. Moreover, LTRs resulted in CD4+ T-cell responses to Omicron sublineages with comparable reactivity to those in HDs.

a Comparison of spike-specific Th1 CD4+ T-cell frequency against spike peptides in CD4+ total memory Tcells at pre-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). b Fold-change of spike-specific Th1 CD4+ T-cell frequency against variants of concern at pre-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. c Comparison of spike-specific Th1 CD4+ T-cell frequency against spike peptides in CD4+ total memory Tcells at post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). d Fold-change of spike-specific Th1 CD4+ T-cell frequency against variants of concern at post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.

Next, we investigated CD8+ T cell responses to Omicron sublineages. Interestingly, the frequency of spike-specific CD8+ T-cell responses to mutant strains was not significantly decreased, regardless of the pre- and post-third boost (Fig.6a, b). The fold-changes in the frequency of CD8+ T-cell responses to mutant strains relative to Wuhan-1 are shown (Fig.6c, d). Collectively, these results demonstrate that mRNA vaccines induce CD8+ T-cell responses reactive to BA.5, BQ.1.1, and XBB mutant strains and that these responses are maintained in LTRs.

Comparison of spike-specific CD69+4-1BB+ CD8+ T-cell frequency against spike peptides in CD8+ total memory Tcells at (a) pre- and (b) post-third boost (HDs: black, CNI: red, CNI+other drug(s): blue). Fold-change of spike-specific CD8+ T-cell frequency against variants of concern at (c) pre- and (d) post-third boost relative to Wuhan-1. The minus symbol denotes increased resistance. Shades of blue represent an increase in fold change, with darker shades indicating a larger positive fold change. Conversely, shades of red denote a decrease, with darker shades signifying a larger negative fold change. P values (two-sided) were calculated using the Wilcoxon matched-pairs signed rank test. Sample size, 1m after 2nd: 23 vs 17 vs 26, 3m after 2nd: 22 vs 16 vs 22, 6m after 2nd: 43 vs 21 vs 29, 1m after 3rd: 43 vs 20 vs 29. All experiments were performed once. Error bars indicate the interquartile range.

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Humoral and cellular immune responses to COVID-19 mRNA vaccines in immunosuppressed liver transplant ... - Nature.com

Human Rights Act

The states supreme court found the vaccine rules for police were unlawful and those for paramedics were ineffective. Heres what the judgment means

Wed 28 Feb 2024 01.34 EST

The Queensland supreme court has thrown out the states Covid-19 vaccination mandate for paramedics and police, on the basis of the Human Rights Act.

Guardian Australia spoke to a range of human rights experts to understand the ramifications of Tuesdays decision.

What does the decision mean?

It means 74 named applicants to the court, who are current employees of the ambulance and police services, cannot be fired or otherwise disciplined as a result of not following the vaccine mandate.

What was the basis for the decision?

There were essentially two different reasons for the decision, depending on whether applicants worked for the police force or Queensland health.

Senior judge administrator Glenn Martin ruled that police commissioner, Katarina Carroll, didnt follow the right process under the Human Rights Act and failed to give proper consideration to human rights relevant to those decisions. As a result, those decisions were unlawful.

The courts decision was even more technical with regard to the ambulance service. That application succeeded because the health service was unable to provide sufficient evidence to show that the order was a power contained in an employment contract. The ambulance service order was not unlawful, just ineffective.

Griffith University human rights law professor Sarah Joseph described it as a procedural rather than substantive breach of the act, and a narrow decision.

Is the decision final?

Not necessarily. It could be appealed in the supreme court of appeal. Both Queensland health and the Queensland police said on Tuesday they were considering their legal options.

How did this happen in the first place?

The applicants challenged two decisions in 2021 and 2022 by the commissioner of police, and the then director general of Queensland health, Dr John Wakefield, that staff must be vaccinated against Covid-19 or else face disciplinary action or even sacking. Both mandates were quashed, in December 2022 and September 2023, respectively.

After a 21-month wait, a joint judgment was handed down on Tuesday at the Queensland supreme court. Its the first time a vaccine mandate has failed in court in Australia.

What does this mean for other states?

The decision is very narrow and based on the state Human Rights Act, which only applies in Queensland. It is also based entirely on the way Queensland decision-makers issued that specific mandate.

The only other state with a Human Rights Act is Victoria, which has a similar requirement for government to consider human rights when making decisions. The ACT also has a Human Rights Act.

Theoretically, lawyers in those jurisdictions could make out a similar case that their state decision-makers failed to consider human rights properly before imposing vaccination mandates.

Does it mean all vaccine mandates are illegal?

Definitely not.

In fact the court has explicitly ruled otherwise.

Queensland health has imposed all sorts of vaccine mandates on its staff for a very long time. Nurses, doctors, paramedics and even health volunteers have to be vaccinated against various diseases, ranging from tuberculosis to whooping cough, to keep their job. They still do and these rules are all still legal.

On Tuesday, the health minister, Shannon Fentiman, told media the decision did not affect the health directive imposed on the broader community of employees of Queensland health, including doctors and nurses, only employees of the ambulance service.

Martin was asked to rule that the mandate violated rights against discrimination, to equality before the law, against torture, to freedom of political thought and belief, to privacy, to life, to take part in public life and the right to liberty and security, among others. He ruled none of these rights were limited at all.

The only right that was impeded, he found, was the right not to be subjected to medical treatment without consent. Martin found public servants were coerced into vaccination because they feared loss of employment and income.

However, the states Human Rights Act does allow rights to be limited, the limits just need to be demonstrably reasonable.

Martin ruled that the restriction of that right was reasonable given the circumstances of the pandemic.

However, the act doesnt just require a decision-maker to come to the right decision they also have to do it the correct way, and document this process.

Some lawyers say if the police commissioner had done so, the court might have ruled a different way on the police element of the case.

Does it mean sacked police and paramedics can sue for compensation?

Billionaire businessman Clive Palmer who says he provided millions for the successful case said he would be happy to fund future legal action, potentially a class action lawsuit.

Lawyers for the police applicants also hinted at civil litigation in the future.

Human rights professor Sarah Joseph said she couldnt predict how compensation claims would play out, but said the chances of winning a litigation lawsuit against the government today are much bigger than they were yesterday.

Benedict Coyne, who acted for many of the police service employees in the case, said the case would have a significant impact on others outside the group of litigants, including officers who were sacked as a result of the mandates.

What does this mean for the state Human Rights Act?

Human rights advocates have celebrated the outcome.

In a state without an upper house, Queensland has often been said to have an accountability deficit in its government.

Its now clear the act is capable of acting as a check on the actions of governments.

Michael Cope, the president of the Queensland Council for Civil Liberties, said some elements of the judgment represented the first time sections of the Human Rights Act had been tested in the supreme court, blazing a precedent for future cases.

This is a reminder to everybody that that is the law in this state and if you dont do it, you can have your decision declared to be in breach of the Human Rights Act, Cope said.

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What does Queenslands Covid-19 mandates ruling mean for other vaccines and other states? - The Guardian