Most vaccines contain an infectious pathogen or a part of it, but mRNA vaccines deliver the genetic instructions for our cells to make viral or bacterial proteins themselves. Our immune system responds to these and builds up immunity.

How do mRNA vaccines work
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Messenger RNA (mRNA) is a single-stranded molecule naturally present in all of our cells. It carries the instructions for making proteins from our genes, located in the cell nucleus, to the cytoplasm, the main body of our cells.

Enzymes in the cytoplasm then translate the information stored in mRNA and make proteins.

An mRNA vaccine delivers the instructions for making a bacterial or viral protein to our cells. Our immune system then responds to these proteins and develops the tools to react to future infections with the pathogen.

mRNA vaccine technology is not new, but there were no mRNA vaccines that had approval for use in humans until recently.

What is different about mRNA vaccines?

Some vaccines use a whole virus or bacterium to teach our bodies how to build up immunity to the pathogen. These pathogens are inactivated or attenuated, which means weakened. Other vaccines use parts of viruses or bacteria.

Recombinant vaccine technology employs yeast or bacterial cells to made many copies of a particular viral or bacterial protein or sometimes a small part of the protein.

mRNA vaccines bypass this step. They are chemically synthesized without the need for cells or pathogens, making the production process simpler. mRNA vaccines carry the information that allows our own cells to make the pathogen’s proteins or protein fragments themselves.

Importantly, mRNA vaccines only carry the information to make a small part of a pathogen. From this information, it is not possible for our cells to make the whole pathogen.

Both mRNA COVID-19 vaccines that Pfizer/BioNTech and Moderna have developed cannot cause COVID-19. They do not carry the full information for our cells to make the SARS-CoV-2 virus, and therefore, cannot cause an infection.

While the concept of mRNA vaccines may seem simple, the technology is rather sophisticated.

Addressing stability and safety

RNA is a notoriously fragile molecule. Delivering mRNA successfully to cells inside our bodies and ensuring that enzymes within our cells do not degrade it are key challenges in vaccine development.

Chemical modifications during the manufacturing process can significantly improve the stability of mRNA vaccines.

Encapsulating mRNA in lipid nanoparticles is one way to ensure that a vaccine can successfully enter cells and deliver the mRNA into the cytoplasm.

mRNA does not linger in our cells for long. Once it has passed its instructions to the protein-making machinery in our cells, enzymes called ribonucleases (RNases) degrade the mRNA.

It is not possible for mRNA to move into the nucleus of a cell as it lacks the signals that would allow it to enter this compartment. This means that RNA cannot integrate into the DNA of the vaccinated cell.

There is no risk of long-term genetic changes with mRNA vaccines.

The mRNA COVID-19 vaccines by Pfizer and Moderna have undergone safety testing in human clinical trials.

The United States Food and Drug Administration (FDA) have granted Emergency Use Authorization (EUA) for the Pfizer mRNA vaccine after reviewing the safety data from over 37,000 trial participants.

“The most commonly reported side effects, which typically lasted several days, were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever,” the FDA wrote in their statement. “Of note, more people experienced these side effects after the second dose than after the first dose, so it is important for vaccination providers and recipients to expect that there may be some side effects after either dose, but even more so after the second dose.”

 

Source: https://www.medicalnewstoday.com/articles/how-do-mrna-vaccines-work#Addressing-stability-and-safety 

 

People all around the world have been recounting their experiences with “long COVID” — a state of illness that lasts weeks or months longer than doctors expect. In a recent BMJ webinar, specialists have discussed how best to support people in this situation.

In a recent BMJ webinar, specialists have discussed long COVID and suggested ways forward for healthcare practitioners.

As a recent Medical News Today feature has highlighted, an increasing number of people around the world have reported lasting illness following confirmed or suspected infection with SARS-CoV-2, the virus that causes COVID-19.

The symptoms involved — often extreme fatigue and fever — persist for many weeks or months after they are supposed to have disappeared.

This phenomenon is now often dubbed long COVID, and the people affected sometimes call themselves “long-haulers.”

Besides explaining how the lingering symptoms have drastically reduced their quality of life, long-haulers also note that, more often than not, healthcare practitioners are at a loss as to how to provide support.

To begin to address this gap in primary care, some specialists have been drafting new guidelines for doctors.

In a BMJ webinar that took place at the start of September, six specialists from the United Kingdom and Germany came together to discuss the best approaches to the diagnosis, management, and prognosis of long COVID.

They were: Prof. Paul Garner, from the Liverpool School of Tropical Medicine; Prof. Nisreen Alwan, from the University of Southampton; Prof. Trish Greenhalgh, from the University of Oxford; Dr. Valentina Puntmann, from University Hospital Frankfurt; Prof. Nicholas Peters, from Imperial College London; and Prof. Tim Spector, from King’s College London.

Symptoms and definition

As Dr. Fiona Godlee, the editor-in-chief of BMJ and chair of the session, noted: “While most people recover quickly and completely from COVID-19, growing numbers are finding that they haven’t simply snapped back into their pre-COVID lives. Instead, after what may have been only a mild initial illness, they are experiencing a range of troubling and sometimes disabling symptoms.”

“Breathlessness, cough, palpitations, exercise intolerance, mental and physical exhaustion, anxietydepression, fatigue, inability to concentrate and brain fog are just some of the things being described,” she said.

Yet despite living with such life-altering symptoms for months, many people are unable to convince their doctors that they have long COVID, having never received a positive COVID-19 test result.

According to Prof. Greenhalgh — who specializes in primary care and also works as a general practitioner — the requirement for proof of an infection with SARS-CoV-2 is the first thing that has to change if patients with long COVID are to receive any support.

In a BMJT article she co-authored in August, Prof. Greenhalgh and colleagues had already emphasized this point: “Since many people were not tested, and false-negative tests are common, we suggest that a positive test for [COVID-19] is not a prerequisite for diagnosis.”

Highlighting that there is an “absence of agreed definitions,” she and her team suggested that a helpful approach might be to think of “post-acute COVID-19 as extending beyond 3 weeks from the onset of first symptoms, and chronic COVID-19 as extending beyond 12 weeks,” regardless of any test results.

Pacing is important to recovery

Dr. Puntmann, a specialist in cardiology, spoke of the links between COVID-19 and inflammation of the heart muscle, called myocarditis, which seems to be a long-term effect of infection with SARS-CoV-2.

Prof. Garner, a specialist in infectious diseases, says that he himself is living with long COVID, an experience that he had already described in BMJ.

In the webinar, he emphasized that “Navigating help is really difficult,” and even that “Dealing with [long COVID] is a full-time job,” adding that “We need to be realistic about the time that is needed for convalescence.”

Both Prof. Garner and Prof. Alwan, who specializes in public health and previously had long COVID, noted that fatigue is a very common and often debilitating symptom of the prolonged disease.

For many, Prof. Garner included, trying to get back to work and return to the regular rhythm of activity has impeded their recovery. This is why the experts advised that careful self-pacing is more helpful than trying to force recovery.

Prof. Garner says that he began to understand this when a friend told him to “Stop trying to dominate this virus, [and] try and accommodate it [instead].”

“You have to drop by 90% from what you were doing before. You are a different person, and you have to be very careful about overdoing it, because as soon as you overdo it, you throw yourself back into bed and [feeling] unwell.”

– Prof. Paul Garner

 

Long COVID ‘twice as common in females’

Prof. Spector, a genetic epidemiologist and the lead researcher of the COVID Symptom Study, estimated that around 60,000 people in the United Kingdom have symptoms of COVID-19 that have lasted for more than 3 months.

He also said that the data available to him and his team suggest that long COVID is “twice as common in females as in males” and that it may manifest differently depending on a person’s age.

However, Prof. Spector claimed that based on the information that he and his team have compiled, they might be able to predict with about 75% accuracy who will develop long COVID, which may help efforts to prevent it.

Speaking of managing this long illness, Prof. Greenhalgh went on to say that while people living with long COVID primarily manage their symptoms on their own, there is much more scope for family doctors to offer support.

“[General practitioners] can actually manage most of these patients in general practice,” she explained, “using the clinical skills that [they] already have, and those clinical skills are things like: listening to the patient, documenting when the illness started, documenting what the symptoms are and how they’ve changed and how they fluctuate […], being alert to symptoms that might suggest that the patient needs referring [to various specialists].”

Prof. Greenhalgh noted that its is important for family doctors to keep on “maintaining […] relationship-based care,” which requires “hearing the patient’s story” and following its development to see if the person’s health improves.

If it does not, then general practitioners ought to direct their patients to respiratory clinics or cardiology clinics, depending on the most prominent symptoms, Prof. Greenhalgh explained.

 

Source: https://www.medicalnewstoday.com/articles/long-covid-specialists-lay-groundwork-for-diagnosis-and-management#Long-COVID-twice-as-common-in-females

 

What is C.1.2, and should we worry? 
  • Researchers have identified a new SARS-CoV-2 variant, which they refer to as C.1.2.
  • C.1.2 contains mutations associated with increased transmissibility and ability to evade antibodies than other variants.
  • However, experts say the public should not panic about the C.1.2 variant.
  • They add that public health protocols, such as vaccinations, wearing a mask, and social distancing, are effective ways to prevent infection.

All data and statistics are based on publicly available data at the time of publication. Some information may be out of date. 

The more viruses spread, the more likely they are to mutate and form different variants. Variants that become more transmissible, resistant to current treatment options and vaccines, or cause more severe disease, are called Variants of Concern (VOC).

The World Health Organization (WHO)Trusted Source currently recognizes four SARS-CoV-2 VOCs:

  • Alpha B.1.1.7, first detected in September 2020 in the United Kingdom
  • Beta B.1.351, first detected in May 2020 in South Africa
  • Gamma P.1, first detected in November 2020 in Brazil
  • Delta B.1.617.2, first detected in October 2020 in India

Viruses need a host to replicate and mutate. The only way to stop new and more dangerous variants of SARS-CoV-2 from emerging is to prevent transmission and infection.

SARS-CoV-2 replicates quicker in unvaccinated people and, therefore, the virus has more opportunity to mutate. As these individuals have not already developed an immune response to the virus, it can survive and multiply for longer periods of time in their bodies.

The more opportunity SARS-CoV-2 has to cause infection in unvaccinated individuals, the higher the chance for new VOCs to emerge.

In recent research, scientists from the National Institute for Communicable Diseases (NICD) in Johannesburg, South Africa, alongside other institutions in the country, identified and discussed a new potential Variant of Interest called C.1.2.

Since its initial discovery in May 2021, scientists have detected the C.1.2 variant in seven other countries, including New Zealand, the U.K., and China. While it has some characteristics that may cause concern, experts are still gathering data.

A recent study investigating the variant appears on the preprint server, medRxiv.

Mutations

Using genetic analysis, the study authors note that C.1.2 contains many mutations also present in the Alpha, Beta, Delta, and Gamma variants of SARS-CoV-2. The researchers state these mutations make it easier for the virus to enter target cells, resist current treatments and vaccines, and pass from one person to another.

“​​Scientists are concerned about the variant, because of how quickly it has mutated: it is between 44 and 59 mutations away from the original virus detected in Wuhan, [China] making it more mutated than any other WHO-identified VOC or Variant of Interest,” said Dr. Vinod Balasubramaniam, senior lecturer at Monash University of Malaysia, who was not involved in the study.

“It also contains many mutations that have been associated with increased transmissibility and a heightened ability to evade antibodies in other variants,” the scientists said, “though they occur in different mixes, and their impacts on the virus are not yet fully known,” he added.

As the variant has had just a few months to circulate, knowledge on how it works is limited. However, the researchers reported that cases of the variant have increased in recent months at a similar rate to the Beta and currently dominant Delta variants as they began to spread in South Africa.

In May, C.1.2 accounted for 0.2% of genomes sequenced, in June, 1.6%, and in July, 2.0%.

The researchers also note there is usually a delay of 2–4 weeks between sampling and data being publicly available. This, alongside limitations in their sampling capacity, may mean the variant is more common than current data suggests.

Where did C.1.2 come from? 

“Viruses mutate in part as a result of an immune attack,” Dr. Cathrine Scheepers, first author of the study and senior medical scientist at the NICD in South Africa, told Medical News Today, “When someone [acquires an infection] with a virus, our antibodies bind onto this virus to kill it and prevent it from getting into our cells.

“During infection, the virus will mutate randomly. If these random mutations confer a benefit, such as the ability to evade these immune attacks by preventing antibody binding, that mutation will increase in number, as viruses with that mutation have a competitive advantage,” she continued.

“The longer somebody [has an infection] with a particular virus, the more chance it has to accumulate a lot of mutations. Since this lineage (C.1.2) is so highly mutated, we hypothesize it is a result of a prolonged infection allowing the virus to accumulate many mutations before being transmitted to others,” she added.

Source: https://www.medicalnewstoday.com/articles/covid-19-what-do-we-know-about-the-c-1-2-variant 

As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. Researchers from the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have now shown that the reduced stem cell function upon ageing is due to changes in their epigenome. They were able to reverse these changes in isolated stem cells by adding acetate. This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis.

Ageing Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA. The Cologne research group of Peter Tessarz has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

"We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice," explains Andromachi Pouikli, first author of the study. "We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected."

Rejuvenation of the epigenome

The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. "This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells," Pouikli said.

To clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.

A new therapeutic approach against osteoporosis?

"Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells. However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects," explains Peter Tessarz, who led the study.

 

Source: https://www.sciencedaily.com/releases/2021/09/210914124958.htm 

Adults with normal blood pressure and high levels of stress hormones were more likely to develop high blood pressure and experience cardiovascular events compared to those who had lower stress hormone levels, according to new research published today in Hypertension, an American Heart Association journal.

Studies have shown that cumulative exposure to daily stressors and exposure to traumatic stress can increase cardiovascular disease risk. A growing body of research refers to the mind-heart-body connection, which suggests a person's mind can positively or negatively affect cardiovascular health, cardiovascular risk factors and risk for cardiovascular disease events, as well as cardiovascular prognosis over time.

"The stress hormones norepinephrine, epinephrine, dopamine and cortisol can increase with stress from life events, work, relationships, finances and more. And we confirmed that stress is a key factor contributing to the risk of hypertension and cardiovascular events," said study author Kosuke Inoue, M.D., Ph.D., assistant professor of social epidemiology at Kyoto University in Kyoto, Japan. Inoue also is affiliated with the department of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles.

"Previous research focused on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension. However, studies looking at adults without hypertension were lacking," Inoue said. "It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events."

Study subjects were part of the MESA Stress 1 study, a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA), a large study of atherosclerosis risk factors among more than 6,000 men and women from six U.S. communities. As part of MESA exams 3 and 4 (conducted between July 2004 and October 2006), white, Black and Hispanic participants with normal blood pressure from the New York and Los Angeles sites were invited to participate in the substudy MESA Stress 1. In this substudy, researchers analyzed levels of norepinephrine, epinephrine, dopamine and cortisol -- hormones that respond to stress levels. Hormone levels were measured in a 12-hour overnight urine test. The substudy included 412 adults ages 48 to 87 years. About half were female, 54% were Hispanic, 22% were Black and 24% were white.

Participants were followed for three more visits (between September 2005 and June 2018) for development of hypertension and cardiovascular events such as chest pain, the need for an artery-opening procedure, or having a heart attack or stroke.

Norepinephrine, epinephrine and dopamine are molecules known as catecholamines that maintain stability throughout the autonomic nervous system -- the system that regulates involuntary body functions such as heart rate, blood pressure and breathing. Cortisol is a steroid hormone released when one experiences stress and is regulated by the hypothalamic-pituitary-adrenal axis, which modulates stress response.

"Although all of these hormones are produced in the adrenal gland, they have different roles and mechanisms to influence the cardiovascular system, so it is important to study their relationship with hypertension and cardiovascular events, individually," Inoue said.

Their analysis of the relationship between stress hormones and development of atherosclerosis found:

  • Over a median of 6.5-year follow-up period, every time the levels of the four stress hormones doubled was associated with a 21-31% increase in the risk of developing hypertension.
  • During a median of 11.2-years of follow-up, there was a 90% increased risk of cardiovascular events with each doubling of cortisol levels. There was no association between cardiovascular events and catecholamines.

"It is challenging to study psychosocial stress since it is personal, and its impact varies for each individual. In this research, we used a noninvasive measure -- a single urine test -- to determine whether such stress might help identify people in need of additional screening to prevent hypertension and possibly cardiovascular events," Inoue said.

"The next key research question is whether and in which populations increased testing of stress hormones could be helpful. Currently, these hormones are measured only when hypertension with an underlying cause or other related diseases are suspected. However, if additional screening could help prevent hypertension and cardiovascular events, we may want to measure these hormone levels more frequently."

A limitation of the study is that it did not include people who had hypertension at the study's start, which would have resulted in a larger study population. Another limitation is that researchers measured stress hormones via a urine test only, and no other tests for stress hormone measurement were used.

Co-authors are Tamara Horwich, M.D.; Roshni Bhatnagar, M.D.; Karan Bhatt; Deena Goldwater, M.D., Ph.D.; Teresa Seeman, Ph.D.; and Karol E. Watson, M.D., Ph.D.

The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, the Barbara Streisand UCLA Women's Health Program, the National Institutes of Health, the Toffler Award at UCLA and the Honjo International Foundation Scholarship.

 

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