How Gut Bacteria Changes the Immune System

By Dr. Narveen Jandu  

The human immune system changes with age. Immune responses start to become less robust as people get older, which makes them more vulnerable to certain infections and diseases.

However, immune system aging looks different from person to person. Research has shown that changes to the composition and diversity of the microorganisms in the gut may explain these differences in immune system aging.

The gut microbiome — the population of microorganisms that lives in the gastrointestinal tract — helps the body maintain a stable internal environment when it is faced with external changes. This is known as homeostasis. The gut microbiome supports homeostasis in different ways, such as through helping to keep the immune system alert, and digesting dietary fibre into short-chain fatty acids to strengthen the intestinal wall.

The gut microbiome also helps us to regulate our inflammatory reactions. Inflammation helps the body fight microorganisms that cause disease, and helps repair damaged tissues. However, as the composition of our gut microbiome changes with age, a low level of inflammation can become constant throughout the body. This is called inflammaging.

When inflammaging develops in the gut, it leads to a decrease in immune responses, which puts people at a higher risk for infection and disease.

Let’s take a closer look at the gut microbiome and how it changes with age.

Diversity of Bacteria Decreases with Age

Our gastrointestinal tract can be compared to a densely populated city inhabited by a variety of different bacteria, fungi, archaea and viruses collectively called the gut microbiota. In fact, compared to other parts of the body, the gut microbiome has the largest number of bacteria. In a healthy gut microbiome, there are four dominant families (or phyla) of microorganisms, including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria.

Firmicutes and Bacteroidetes make up around 80 to 90 per cent of the gut microbiota in the digestive tract. Firmicutes help with the production of short-chain fatty acids to support intestinal health and the secretion of mucus to improve intestinal wall defence. Bacteroidetes metabolize complex carbohydrates into vitamins and nutrients, and help promote glycogen storage to improve glucose metabolism.

The gut microbiome and immune system work closely together. The microorganisms in the gut send out signals that are detected by immune sensors. This allows the immune system to regulate the beneficial bacteria in the gut, helping maintain immune homeostasis. Through this interaction, the adaptive immune system also receives stimuli from harmful substances called antigens, which trigger an immune reaction.

However, as people age, the composition and balance of microorganisms in the gut changes. This gives rise to microbial dysbiosis, which means there is a reduction in the number of beneficial bacteria in the gut, alongside a higher number and pro-inflammatory organisms and bacteria that can cause disease. In addition to this, research has also shown that the general diversity of bacteria in our gut also decreases with age.

Over time, the shortage of beneficial bacteria such as Firmicutes in older adults starts to compromise the integrity of their intestinal barrier, causing it to become leaky. This is because the Firmicutes family plays a very important role in keeping the intestinal wall healthy and strong by producing a short-chain fatty acid called butyrate. Short-chain fatty acids such as butyrate help provide nutrients to strengthen the intestinal wall, inform immune responses and lower inflammation.

When intact, the intestinal barrier works to prevent harmful bacteria from passing through the intestinal wall, entering the circulatory system and reaching important organs. However, when there are not enough gut bacteria to produce the short-chain fatty acids that are needed for the intestinal wall to function, bacteria are able to enter the bloodstream. This contributes to the formation of intestinal inflammaging, which refers to a low level of inflammation that becomes steady throughout the body with age.

Inflammaging creates an environment that is prone to inflammation, which is caused and maintained by several factors. These can include microorganism imbalances in the intestines (microbial dysbiosis), psychological stress, physical inactivity, poor nutrition and chronic infections.

When the body is exposed to these factors on a regular basis, cellular senescence occurs. Cellular senescence is a state in which cell growth is permanently arrested, which means that cells are no longer able to self-renew. Eventually, this leads to a decrease in immune responses, which are important to prevent foreign substances and pathogens from entering the body.

How to Maintain a Healthy Balance of Bacteria

There is a common saying that claims “you are what you eat.” Indeed, nutrition and diet play an important role in regulating the number of different microorganisms that live in the gut. This means that diet may also play a key role in the immune function of older adults.

The Mediterranean diet, known for its lower intake of refined carbohydrates, saturated fats, dairy products and red meat, has been shown to have a positive effect on the balance of microorganisms in the gut and the strength of the intestinal barrier. The Mediterranean diet has also been linked to a lower risk of Type 2 diabetes in older adults, allowing these individuals to live a longer and healthier life.

The use of probiotics and prebiotics can also help fight age-related inflammation. Probiotics, such as Lactobacilli and Bifidobacteria, are live microorganisms that can be consumed to support overall health. More specifically, probiotics help improve the function of the intestinal barrier and regulate immune responses by modifying the composition of the gut microbiome. However, there is still some debate around whether the acidic conditions in the stomach allow probiotics to survive long enough to be able to move into the intestine.

It is clear that the immune system has an intricate relationship with the gut microbiome. A healthy and well-balanced gut microbiome will strengthen the intestinal barrier, which helps to reduce inflammation throughout the body and support the immune system.

To achieve this, it is important to maintain a healthy and well-balanced lifestyle as we grow older. This can include lower intake of dairy products and red meats, and harnessing the benefits of probiotics and prebiotics.

Narveen Jandu, PhD, is a faculty member with the School of Public Health Sciences at the University of Waterloo in Canada. As a biomedical researcher, Dr. Jandu’s research has focused on studying the cellular mechanisms and pathophysiological consequences of infectious diseases.

This article was co-authored by Flore Van Leemput. a student in health sciences at the University of Waterloo.

This article originally appeared in The Conversation and is republished with permission.

Lyme Disease: How a Bacteria Plays Havoc with Immune Systems

By Dr. Jenny Wachter, University of Saskatchewan

Lyme disease is the leading vector-borne disease — meaning diseases that are transmitted to humans from another organism like a tick or mosquito — in North America and Europe.

New human cases are estimated at over 400,000 in the United States each year. Canada has experienced a drastic increase in human cases, from 266 cases in 2011 to 3,147 in 2021, as the habitat of its vector, a tick, expands north.

The initial symptoms of human Lyme disease can be vague, such as fever, headache, fatigue and often rash. It is a potentially serious condition that can affect multiple systems in the body — including the heart, nervous system and joints — and can become a chronic illness.

Lyme disease is caused by a unique, spiral-shaped (spirochete) bacterium called Borrelia burgdorferi. B. burgdorferi cannot survive in the environment on its own. For survival and transmission, it requires susceptible hosts (usually small mammals or birds) and a specific vector: the black-legged tick, also called the deer tick.

Evading the Immune System

B. burgdorferi must survive extremely diverse conditions over the course of its transmission and infection cycle: from host to tick vector, and then into new hosts.

This bacterium senses and responds to its surroundings, most notably by modifying its appearance by changing the proteins on its outer surface to help it survive in either the tick or the host.

When a tick infected by B. burgdorferi bites and feeds on a vertebrate host, it provides a signal for the bacteria to switch its proteins to those required to infect the host, and to begin migrating through the tick and into the bite site. This process takes between 36 and 72 hours.

However, many of these proteins are recognized by the host as foreign, and the host’s immune system works to try to clear the infection. This includes a strong, antibody response targeted against B. burgdorferi.

Despite these immune responses, B. burgdorferi is able to cause long-term infections. In natural host reservoirs — the animals that the bacterium usually finds itself in via tick bites, such as small rodents — these infections do not cause diseases like those seen in humans and other non-natural reservoirs.

In fact, the bacteria itself does not produce any products that would be toxic to its hosts, either natural or non-natural. Yet chronic infection in humans can lead to Lyme neuroborreliosis, carditis and Lyme arthritis.

How then, are these bacteria able to cause such a devastating disease in humans and other animals, but not in their natural host reservoirs?

While there is still much to learn about B. burgdorferi, we know of several factors that play a role in the range of disease it causes. These include:

• its genetic make-up,

• its ability to access various tissues (such as the joints, heart and nervous system) due to its ability to move around (motility), and

• the immune response of the host.

Apart from motility, B. burgdorferi also protects itself from the strong B. burgdorferi-specific targeted antibody response of its host’s immune system by changing the appearance of the main outer surface protein expressed during persistent infection in a process called antigenic variation.

In addition to antigenic variation, B. burgdorferi bacteria can also change their DNA by exchanging genetic information, a process also known as gene transfer. This process allows these bacteria to further alter their appearance during infection to avoid the host immune system.

This process works so well that these B. burgdorferi bacteria appear different enough to allow re-infection or even co-infection (where multiple strains of B. burgdorferi infect a single host at the same time) of a vertebrate host, like a mouse or a human, despite the presence of specific antibodies to fight the bacterium.

In fact, in nature, the majority of host reservoirs and the ticks that carry the bacterium are infected with multiple strains of B. burgdorferi. The ability of B. burgdorferi to reinfect and co-infect both ticks and hosts increases the spread of the bacteria in the environment as well as the chances that humans will encounter Lyme disease.

Human Cases of Lyme Disease Are Increasing

As a vector-borne pathogen, B. burgdorferi only infects individuals that are bitten by an infected tick. It is not transmitted from person to person.

Environments that support black-legged/deer ticks are at risk of harbouring B. burgdorferi. In North America, these species of ticks are widely distributed throughout the eastern and midwestern United States. Recent geographic expansion to the north is increasing the prevalence of Lyme disease in Canada.

The increase of human Lyme disease cases highlights the failure of existing preventive strategies — such as minimizing exposure to tick habitats, performing diligent tick checks, and wearing suitable clothing when performing activities in known tick habitats — and emphasizes the need for an effective human vaccine.

At Vaccine and Infectious Disease Organization at the University of Saskatchewan, we are taking a One Health approach by recognizing that human health is closely related to the health of animals and the shared environment. We are investigating the role of B. burgdorferi, ticks, and susceptible animals on the spread and survival of the Lyme disease bacterium.

It is important to mimic the natural infectious cycle as much as possible when identifying potential vaccine and drug targets. This is because the way host animals are infected (for example, artificial needle infection or natural tick bite) can produce drastic differences in the resulting infection.

Additionally, despite the prevalence of this disease, there are still many aspects of the infectious cycle that remain unknown due to the uniqueness of B. burgdorferi and a lack of knowledge about the tick vector.

For example, we recently learned that a B. burgdorferi protein is responsible for regulating the components necessary for the bacterium to infect vertebrates, including humans. The absence of this protein, among other things, leads to the death of B. burgdorferi in ticks, making it an exciting target for research investigation.

By learning more about the molecular mechanisms that change or reduce the severity of the disease caused by this bacterium, we can identify new targets for the prevention of human Lyme disease. 

Jenny Wachter, PhD, is a research scientist and adjunct professor at University of Saskatchewan.

This article originally appeared in The Conversation and is republished with permission.

How Inflammation Can Lead to Chronic Pain

By Drs. Prakash Nagarkatti and Mitzi Nagarkatti, University of South Carolina

When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of inflammation occurring in the body.

We are two immunologists who study how the immune system reacts during infections, vaccination and autoimmune diseases where the body starts attacking itself.

While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.

Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are five classic physical signs of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.

Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system deploys various types of immune cells to the site of the sting. These include T cells, B cells, macrophages and neutrophils, among other cells.

The B cells produce antibodies. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. Macrophages and neutrophils engulf bacteria and destroy them. T cells don’t produce antibodies, but kill any virus-infected cell to prevent viral spread.

Collateral Damage

Additionally, these immune cells produce hundreds of types of molecules called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.

The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells.

This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.

After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed.

Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or becomes chronic, the damage it causes can be harmful.

Allergies, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.

Chronic inflammation damages tissues over time and can lead to many noninfectious clinical disorders, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers.

The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of autoimmune diseases such as lupus and arthritis.

Another cause of chronic inflammation that researchers like us are currently studying is defects in the mechanisms that curtail inflammation after the body clears an infection.

While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown to regulate inflammation in some way.

There is still a lot to be learned about what leads to harmful forms of inflammation, but a healthy diet and avoiding stress can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.

Prakash Nagarkatti, PhD, and Mitzi Nagarkatti, PhD, are Professors of Pathology, Microbiology and Immunology at the University of South Carolina. They receive funding from the National Science Foundation and the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

Brain Changes Found in Patients with Long-Term Lyme Disease

By Pat Anson, PNN Editor

Researchers at Johns Hopkins University have documented changes in the brains of patients with post-treatment Lyme disease that may explain symptoms such as brain fog, memory loss and other cognitive issues. The finding could also have implications for patients with long covid, fibromyalgia, multiple sclerosis, chronic fatigue and other health conditions who have cognitive problems.    

Lyme disease is a bacterial illness spread by ticks that causes a rash, flu-like aches and fever, joint pain and fatigue. Most patients fully recover when treated early with antibiotics, but up to 20% of those with post-treatment Lyme disease (PTLD) have long-term symptoms, including depression, insomnia and cognitive difficulties. There is usually no clinical or laboratory evidence to explain their ongoing issues.

“Objective biologic measures of post-treatment Lyme symptoms typically can’t be identified using regular MRIs, CT scans, or blood tests,” says John Aucott, MD., director of the Johns Hopkins Lyme Disease Clinical Research Center.

Aucott and his colleagues recruited 12 PTLD patients and 18 people without a history of Lyme to undergo functional MRI (fMRI) scans while performing a short-term memory task. The scans allow investigators to track blood flow and other changes in the brain in real time.

Their findings, published in the journal PLOS ONE, suggest that cognitive difficulties in PTLD patients are linked to functional and structural changes in the “white matter” of the brain, which is crucial for processing and relaying information. The imaging tests revealed unusual activity in the frontal lobe, an area of the brain responsible for memory recall and concentration. Patients with post-treatment Lyme needed longer periods of time to complete the memory task.

“We saw certain areas in the frontal lobe under-activating and others that were over-activating, which was somewhat expected,” said lead author Cherie Marvel, PhD, an associate professor of neurology at Johns Hopkins.

“However, we didn’t see this same white matter activity in the group without post-treatment Lyme.”

To confirm their finding, researchers used another form of imaging called diffusion tensor imaging (DTI) on all 12 patients with Lyme and 12 of the non-Lyme participants. DTI detects the direction of water movement within brain tissue. Water was diffusing, or leaking, in the the same white matter regions identified in the fMRI.

Researchers believe the increased activity they saw in white matter may reflect an immune system response in the PTLD patients, which may also explain cognitive issues in patients with other chronic health conditions.

PLOS ONE

“Results reported here may have implications for other diseases in which white matter pathology has been demonstrated (e.g., multiple sclerosis) or in illnesses in which cognitive complaints follow disease onset,” researchers said. “The use of multimodal neuroimaging methods, like the ones used in the current study, may be a viable approach for obtaining information on brain function and structure to identify biomarkers of disease burden.”

Researchers say larger studies with more patients will be needed to confirm their findings, as well as long-term tracking of brain changes from the initial Lyme infection through development of PTLD.

Nearly 500,000 people are believed to get Lyme disease each year in the United States. Diagnoses of Lyme have soared over the past 15 years, according to a recent analysis of insurance claims that found Lyme cases rose 357% in rural areas and 65% in urban areas. The highest rates of Lyme were in New Jersey, Vermont, Maine, Rhode Island and Connecticut.

Pharmacies Turning Away Patients Seeking 4th Covid Shot

By Liz Szabo, Kaiser Health News

Patients with weakened immune systems — who are at high risk from covid-19 — say pharmacies are turning them away when they seek additional vaccine doses recommended by federal health officials.

Alyson Smith became eligible this month for a fourth vaccine dose because her medications leave her immunocompromised.

Although the Centers for Disease Control and Prevention encourages most adults to receive a total of three mRNA vaccines — two “primary” vaccinations and a booster — the agency now advises people with weak immune systems to receive three primary shots plus a booster, for a total of four doses.

Many people are confused about the difference between a primary vaccine series and a booster. A primary vaccine series helps people build antibodies to a new pathogen, while a booster combats waning immunity.

As Smith learned, many pharmacists are unaware that the CDC’s vaccine guidance has changed.

Smith booked her vaccine appointment online. But when she showed up at a Chicago-area Walgreens for the appointment Jan. 19, an employee told her the pharmacy chain wasn’t administering fourth doses to anyone.

Smith said she’s frustrated that vulnerable people are being forced to make multiple visits to crowded pharmacies and supermarkets, where many customers are unmasked.

“I feel for the pharmacists, because they’re overwhelmed like everyone else,” said Smith, 52. “But two years into the pandemic, there is a corporate responsibility to take action when the guidance comes down.”

In a written statement, Walgreens said it has administered thousands of fourth doses to immunocompromised people. “As vaccination guidelines continue to evolve, we make every effort to continuously update our pharmacy teams.”

(Update: In a conference call on January 26, the CDC told pharmacists that people with moderate to severe immune suppression are eligible for a 4th covid shot. About 7 million Americans can get the extra shot.)

Confusing Vaccine Guidance

The confusion stems from recent updates in vaccine advice for immunocompromised people, as well as a change in the interval between the end of a primary vaccine series and a booster.

• In August, the CDC began allowing immunocompromised people to receive a third dose of mRNA vaccine as part of their primary vaccination.

• In October, the CDC quietly updated its website to allow people with suppressed immune systems to receive a fourth shot as a booster.

• In January, the agency shortened the time that anyone must wait for a booster from six months to five.

People who received the one-dose Johnson & Johnson vaccine are eligible for a single booster, for a total of two shots, according to the CDC.

Given how often vaccine guidelines have been revised in recent months, some pharmacists have had a hard time keeping pace, said Mitchel Rothholz, chief of governance and state affiliates at the American Pharmacists Association. Pharmacy employees have coped with an ever-expanding workload but a deepening shortage of employees during the pandemic, he said.

“I don’t know any provider who wants to turn away a patient,” Rothholz said. “The CDC continues to make updates, and it’s becoming very difficult for providers at the grassroots level to keep up. I can understand why a pharmacist would say, ‘Corporate hasn’t given us the green light.’”

Confusion about who is eligible for a fourth shot “was inevitable, although I’m not saying it’s right or wrong,” he said.

Yet many patients and their doctors are frustrated.

If patients keep up with the latest guidelines, they ask, why can’t their pharmacy?

“It’s ridiculous,” said Dr. Dorry Segev, a transplant surgeon and researcher at Johns Hopkins University. “CDC makes it very clear that it’s allowed, and even people who print out the CDC guidance and take it to their pharmacies are being turned away.”

Charis Hill, 34, joined a chorus of immune-suppressed people venting their concerns on social media in recent days. When Hill tweeted Jan. 21 that Rite Aid should better educate its staff, the retailer tweeted back that day, saying, “We’re very sorry you didn’t have a great experience, Charis. Please check back with us early next month for more information regarding the fourth dose.”

In a written statement, Rite Aid said it continually educates its staff as CDC advice changes, and “is looking into the response that was provided to the customer on social media.”

Dr. Shikha Jain, an assistant professor of medicine at the University of Illinois Cancer Center in Chicago, said patients in rural areas often drive long distances to look for vaccines. One of her patients was “almost in tears” after being turned away. Jain tried to help by calling the pharmacy but was on hold so long that she had to hang up to see patients.

Jain said the CDC needs to do a better job educating doctors, pharmacists, and patients.

The CDC did not respond to a request for comment before publication.

Teresa Strahlman, 61, said she’s immunocompromised due to medications she takes for lupus, an autoimmune disease. But the Maryland woman said she didn’t realize she was eligible for a fourth dose until reading a KHN post on Facebook. “I had no idea, and I have a million doctors,” Strahlman said. “No one has said anything to me.”

The CDC estimates that 2.7% of adults — or 7 million people — are immunocompromised, a group that includes people with medical conditions that dampen their immune response, as well as those taking immune-suppressing drugs because of organ transplants, cancer, or autoimmune diseases.

Some immunocompromised people say that being turned away from a pharmacy is especially frustrating, given all that they have sacrificed during the pandemic.

Linda Rushing, 74, has given up attending church services in person, although she’s deeply religious, because of a weakened immune system that leaves her prone to a variety of infections.

Rushing made three visits to local pharmacies before finding someone to administer her fourth shot.

“It’s a tragedy to need help and not be able to get it,” said Rushing, of Rowlett, Texas, whose daughter and granddaughter are also immunocompromised. “I don’t want covid. I don’t want to give it to anybody, and I’m trying to do everything I can not to die from it.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Long Covid Linked to Overactive Immune System

By Pat Anson, PNN Editor

People who develop long-haul COVID – even when the initial infection was mild or moderate – have a sustained inflammatory response that appears to be the result of an overactive immune system, according to Australian researchers.

Long covid is a poorly understood disorder characterized by body pain, fatigue, cognitive impairment and difficulty sleeping. About a third of people infected with coronavirus develop symptoms that can last for many months.   

“This study provides the strongest evidence to date for a clear biological basis for the clinically apparent syndrome of long COVID,” Professor Anthony Kelleher, Director of the Kirby Institute at UNSW Sydney, said in a press release.

Kelleher and his colleagues analyzed blood samples from 62 patients enrolled in the ADAPT study at St. Vincent’s Hospital, who were diagnosed with COVID-19 between April and July 2020 – before any vaccines were available. The blood samples were collected at three, four and eight months following initial infection, and compared to control groups.

Their study, recently published in the journal Nature Immunology, identified biomarkers of a sustained inflammatory response in long covid patients – suggesting their immune systems were activated by the virus, but then failed to turn off.

“What we’re seeing with long COVID is that even when the virus has completely left the body, the immune system remains switched on. If you measure the same thing after a standard cough or cold, which we did in this study through one of our control groups, this signal is not there. It’s unique to sufferers of long COVID,” said Professor Gail Matthews, who co-leads ADAPT and is Program Head of Vaccine and Therapeutic Research at the Kirby Institute.

“Simply put, when we look carefully at the immune system in people who have had COVID-19 infection, and particularly at those with long COVID, it looks different to what we would expect in healthy individuals. This tells us that there might be something quite unique in the pathophysiology of this disease.”

The study findings are welcome news to covid long-hauler Rick Walters, who contracted COVID in August 2020 and is part of the ADAPT study. Walters continues to have symptoms 17 months later.

“I’m glad that the study has confirmed that long COVID is a valid result of COVID-19 infection and just not something in my head. At first, I thought I would get better, but it became apparent that the damage to my lung was permanent, and I became quite anxious,” he said. “I have had some difficulties adjusting to my current health. COVID should not be taken lightly. I am gradually learning to live with the results.”

“One of the most surprising aspects of our analysis is that people don’t need to have had severe COVID to experience these ongoing immunological changes,” says Dr. Chansavath Phetsouphanh, a senior research associate at the Kirby Institute. “We found that there is a significant and sustained inflammation that indicates prolonged activation of the immune system response detectable for at least eight months following initial infection.”

Researchers hope that a better understanding of how the immune system reacts to the virus will lead to better treatment and management of long covid. There is no data yet to reflect whether variants like Omicron also cause long covid.

Previous studies of long covid have found similarities with autoimmune conditions such as lupus and myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).  

Being fully vaccinated against COVID-19 cuts the risk of developing long covid in half, according to a 2021 study. Researchers at King’s College London looked at data from a mobile app used by millions of people in the UK and found that those who received two doses of the Moderna, Pfizer or AstraZeneca vaccines had significantly lower risk of a “breakthrough” infection that turns into long covid.

Surprise Discovery Could Lead to Vaccine for Rheumatoid Arthritis

By Pat Anson, Editor

A surprise discovery at a university laboratory could lead to a vaccine that can prevent rheumatoid arthritis, a chronic and incurable disease in which the body’s own immune system attacks joint tissues.

Researchers at The University of Toledo years were studying a protein called 14-3-3 zeta and its role in immune system pathologies. Previous studies have suggested the protein could be a possible trigger for rheumatoid arthritis (RA) and other autoimmune conditions that cause pain, inflammation and bone erosion.

But researchers found just the opposite. The team discovered that 14-3-3 zeta proteins may actually help prevent arthritis. When they removed the proteins through gene-editing technology, it caused severe early onset arthritis in laboratory animals.

Realizing that the proteins may be beneficial, the team developed an experimental vaccine using purified 14-3-3 zeta protein grown in a bacterial cell. They found the vaccine promoted a strong, immediate and long-lasting response in rodents that protected them from RA.

"Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine," said Ritu Chakravarti, PhD, an assistant professor at UToledo College of Medicine and lead author of research published in the journal Proceedings of the National Academy of Sciences. "Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field."

In addition to suppressing the immune system response, the vaccine also significantly improved collagen content and bone quality — findings that suggests there could be long-term benefits following immunization.

Currently, rheumatoid arthritis is treated with steroids or medications that suppress the immune system, such as biologics and biosimilar drugs. While those therapies can alleviate pain and reduce inflammation, they can also make patients more vulnerable to infection and, in the case of biologics, are expensive. Biologic drugs can cost $25,000 a year.

“We have not made any really big discoveries toward treating or preventing rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

RA affects about 1.5 million Americans and about one percent of the global population. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Chakravarti. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”

Chakravarti and her colleagues have filed for a patent on their discovery and are seeking pharmaceutical industry partners to fund more research and preclinical trials.

Vaccines Help Some Covid Long Haulers

By Will Stone, Kaiser Health News

An estimated 10% to 30% of people who get covid-19 suffer from lingering symptoms of the disease, or what’s known as “long covid.”

Judy Dodd, who lives in New York City, is one of them. She spent nearly a year plagued by headaches, shortness of breath, extreme fatigue and problems with her sense of smell, among other symptoms.

Dodd worried that this “slog through life” was going to be her new normal. But everything changed after she got her covid vaccine.

“I was like a new person. It was the craziest thing ever,” said Dodd, referring to how many of her health problems subsided significantly after her second shot.

As the U.S. pushes to get people vaccinated, a curious benefit is emerging for those with this post-illness syndrome: Their symptoms are easing and, in some cases, fully resolving after vaccination.

It’s the latest clue in the immunological puzzle of long covid, a still poorly understood condition that leaves some who get infected with wide-ranging symptoms months after the initial illness.

The notion that a vaccine aimed at preventing the disease may also treat it has sparked optimism among patients, and scientists who study the post-illness syndrome are taking a close look at these stories.

“I didn’t expect the vaccine to make people feel better,” said Akiko Iwasaki, an immunologist at the Yale School of Medicine who’s researching long covid.

“More and more, I started hearing from people with long covid having their symptoms reduced or completely recovering, and that’s when I started to get excited because this might be a potential cure for some people.”

While promising, it’s still too early to know just how many people with long covid feel better as a result of being vaccinated and whether that amounts to a statistically meaningful difference.

In the meantime, Iwasaki and other researchers are beginning to incorporate this question into ongoing studies of long haulers by monitoring their symptoms pre- and post-vaccination and collecting blood samples to study their immune response.

There are several leading theories for why vaccines could alleviate the symptoms of long covid: It’s possible the vaccines clear up leftover virus or fragments, interrupt a damaging autoimmune response or in some other way “reset” the immune system.

“It’s all biologically plausible and, importantly, should be easy to test,” said Dr. Steven Deeks of the University of California-San Francisco, who is also studying the long-term impacts of the coronavirus on patients.

Patient Stories Offer Hope

Before getting the vaccine, Dodd, who’s in her early 50s, said she felt as if she had aged 20 years. She had trouble returning to work, and even simple tasks left her with a crushing headache and exhaustion.

“I’d climb the subway stairs and I’d have to stop at the top, take my mask off just to get air,” Dodd said.

After she got her first dose of the Pfizer vaccine in January, many of Dodd’s symptoms flared up, so much so that she almost didn’t get her second dose.

But she did — and a few days later, she noticed her energy was back, breathing was easier and soon even her problems with smell were resolving.

“It was like the sky had opened up. The sun was out,” she said. “It’s the closest I’ve felt to pre-covid.”

In the absence of large studies, researchers are culling what information they can from patient stories, informal surveys and clinicians’ experiences. For instance, about 40% of the 577 long-covid patients contacted by the group Survivor Corps said they felt better after getting vaccinated.

Among the patients of Dr. Daniel Griffin at Columbia University Medical Center in New York, “brain fog” and gastrointestinal problems are two of the most common symptoms that seem to resolve post-vaccination.

Griffin, who is running a long-term study of post-covid illness, initially estimated that about 30% to 40% of his patients felt better. Now, he believes the number may be higher, as more patients receive their second dose and see further improvements.

“We’ve been sort of chipping away at this [long covid] by treating each symptom,” he said. “If it’s really true that at least 40% of people have significant recovery with a therapeutic vaccination, then, to date, this is the most effective intervention we have for long covid.”

A small U.K. study, not yet peer-reviewed, found about 23% of long-covid patients had an “increase in symptom resolution” post-vaccination, compared with about 15% of those who were unvaccinated.

But not all clinicians are seeing the same level of improvement.

Clinicians at post-covid clinics at the University of Washington in Seattle, Oregon Health & Science University in Portland, National Jewish Health in Denver and the University of Pittsburgh Medical Center say only a small number of patients — or none at all — have reported feeling better after vaccination.

“I’ve heard anecdotes of people feeling worse, and you can scientifically come up with an explanation for it going in either direction,” said UCSF’s Deeks.

Why Are Patients Feeling Better?

There are several theories for why vaccines could help some patients — each relying on different physiological understandings of long covid, which manifests in a variety of ways.

“The clear story is that long covid isn’t just one issue,” said Dr. Eric Topol, director of the Scripps Research Translational Institute, which is also studying long covid and the possible therapeutic effects of vaccination.

Some people have fast resting heart rates and can’t tolerate exercise. Others suffer primarily from cognitive problems, or some combination of symptoms like exhaustion, trouble sleeping and issues with smell and taste, he said.

As a result, it’s likely that different therapies will work better for some versions of long covid than others, said Deeks.

One theory is that people who are infected never fully clear the coronavirus, and a viral “reservoir,” or fragments of the virus, persist in parts of the body and cause inflammation and long-term symptoms, said Iwasaki, the Yale immunologist.

According to that explanation, the vaccine might induce an immune response that gives the body extra firepower to beat back the residual infection.

“That would actually be the most straightforward way of getting rid of the disease, because you’re getting rid of the source of inflammation,” Iwasaki said.

Griffin at Columbia Medical Center said this “viral persistence” idea is supported by what he’s seeing in his patients and hearing from other researchers and clinicians. He said patients seem to be improving after receiving any of the covid vaccines, generally about “two weeks later, when it looks like they’re having what would be an effective, protective response.”

Another possible reason that some patients improve comes from the understanding of long covid as an autoimmune condition, in which the body’s immune cells end up damaging its own tissues.

A vaccine could hypothetically kick into gear the “innate immune system” and “dampen the symptoms,” but only temporarily, said Iwasaki, who has studied the role of harmful proteins, called autoantibodies, in covid.

This self-destructive immune response happens in a subset of covid patients while they are ill, and the autoantibodies produced can circulate for months later. But it’s not yet clear how that may contribute to long covid, said John Wherry, director of the Institute for Immunology at the University of Pennsylvania.

Another theory is that the infection has “miswired” the immune system in some other way and caused chronic inflammation, perhaps like chronic fatigue syndrome, Wherry said. In that scenario, the vaccination might somehow “reset” the immune system.

With more than 77 million people fully vaccinated in the U.S., teasing apart how many of those with long covid would have improved even without any intervention is difficult.

“Right now, we have anecdotes; we’d love it to be true. Let’s wait for some real data,” said Wherry.

This story is part of a partnership that includes NPR and Kaiser Health News (KHN), a national newsroom that produces in-depth journalism about health issues.

Can Vitamin C Treat COVID-19?

By Madora Pennington, PNN Columnist

Viral infections like COVID-19 are difficult to treat. Unless and until a targeted anti-viral drug or vaccine is developed, symptomatic support is what is given to patients to ease suffering and prolong life -- until their own body hopefully defeats the coronavirus.

While most coronavirus infections are mild or even lack symptoms, to vulnerable patients they can be devastating. The virus can infect various organs, including the brain, lungs and nervous system, which leads to a cascading response of damaging inflammation. Patients can die from respiratory failure or septic shock, ironically caused by an over-reaction of their own immune system battling the virus.

One adjunctive therapy that emerged from the desperation to save patients in Wuhan, China is intravenous ascorbic acid. Yes, that is Vitamin C. A placebo-controlled study has begun in Wuhan to determine if Vitamin C infusions are helpful in treating 140 patients with coronavirus pneumonia. A similar clinical study is underway in Italy.

Doctors in New York are currently administering Vitamin C intravenously to coronavirus patients in large doses that are well above the recommended daily dose.

"I have to hope that this, or any new idea, may help," Peter McCaffery, Professor of Biochemistry at the University of Aberdeen in the UK, told Newsweek.  

"Just to reiterate though, taking large doses of Vitamin C tablets would be very unlikely to protect you from COVID-19 -- unless you were actually Vitamin C deficient, which with a normal diet is quite rare."

McCaffery says Vitamin C is relatively safe because, unlike many other vitamins, it does not build up to toxic levels. The worst side-effect is a potential kidney stone. Large amounts of C taken orally can also upset the stomach.

Previous studies have found that Vitamin C can help prevent death from the deadly complication of sepsis. Scientists believe Vitamin C stops the surge of immune cells that lead to lung destruction and helps reduce fluid buildup in the lungs. Vitamin C helps modulate the immune system, meaning it helps the immune system function properly, not over-reacting and not under-reacting. It also has antiviral properties.

Important for Overall Health

Vitamin C is critical for the maintenance of body functions and normal physiology. It helps the body maintain homeostasis -- the constant adjustments the body makes to keep conditions stable. For example, when a person eats and experiences a rise in glucose, insulin is produced to bring sugar levels down to normal. A breakdown in the body’s ability to maintain homeostasis is what leads to diabetes.

Vitamin C is essential for the formation of collagen, which is everywhere in the human body, gluing everything together. It is necessary for wound healing.

Vitamin C also supports the development of neurons and plays a role in learning and memory. Studies have shown that people with higher concentrations of Vitamin C are more cognitively intact compared to cognitively impaired individuals.

Some studies have shown Vitamin C can shorten the length of a cold, prevent it entirely under certain circumstances, and also reduce flu symptoms. But more research is needed in this area because findings have been mixed. Scientists suspect inconsistent results may be due to the variability of an individual’s ability to absorb Vitamin C and handle oxidative stress.

Some people need more Vitamin C than others to achieve healthy levels of ascorbic acid. Oxidative processes are especially altered in patients with obesity, cancer, neurodegenerative diseases, hypertension and autoimmune diseases. Lower concentrations of Vitamin C are also found in patients with metabolic syndrome.

Nearly all mammals manufacture their own Vitamin C when they are ill or injured. But chimpanzees and humans have a broken copy of the C manufacturing gene. We must obtain ours from food.

During the Age of Sail, a disease of profound Vitamin C deficiency — scurvy — killed an estimated 2 million sailors. At the time, no one knew Vitamin C was such a vital nutrient. Ships set sail on long voyages without enough food that contained it.

Scurvy was a terrible disease and a terrible way to die. Initially overcome with severe fatigue and weakness, sailors became unable to think or work. This created suspicion that laziness itself caused this mysterious disease.

As the body became more and more depleted of Vitamin C, healed fractures re-broke. Old wounds reopened and bled. Bruises formed at the slightest touch. Gums bled and teeth fell out. Joints ached. Flesh turned black and gangrenous. Fatal aortic ruptures or brain bleeding came on suddenly. Scurvy this severe is rarely seen in the modern world.

My interest in Vitamin C is very personal. I have an inherited collagen disorder called Ehlers-Danlos Syndrome (EDS), a poorly understood disease. Vitamin C loading is recommended for my condition, as many of my symptoms are similar to scurvy.

My doctor and I discovered I benefit exponentially from injecting Vitamin C, rather than taking it orally. Why is a mystery. For those interested in oral supplementation, liposomal C is the best choice.

Madora Pennington writes about Ehlers-Danlos and life after disability at LessFlexible.com. Her work has also been featured in the Los Angeles Times.

Confusion Over Ibuprofen as Coronavirus Treatment

By Pat Anson, PNN Editor

With the number of coronavirus cases growing to nearly 200,000 worldwide, so is confusion about which over-the-counter pain reliever should be used to treat its symptoms. Some health experts say acetaminophen – known as paracetamol outside the U.S. – is better than ibuprofen, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs).

"We recommend paracetamol, not ibuprofen for self-medicating," Christian Lindmeier, a spokesman for the World Health Organization said today.

At issue is whether ibuprofen and other NSAIDs interfere with the body’s immune system and make coronavirus symptoms worse. The debate was kicked off Saturday by a tweet from France’s Health Minister.

“Taking anti-inflammatory drugs (ibuprofen, cortisone, ...) could be an aggravating factor of the infection. If you have a fever, take paracetamol,” said Dr. Olivier Véran, a neurologist.

That same day, the French government reported "grave adverse effects" linked to the use of NSAIDs in coronavirus patients and released new guidelines saying “the treatment of a fever or of pain linked to COVID-19 or to any other respiratory viral disease should be paracetamol.”

But the UK’s Royal Pharmaceutical Society (RPS) disputed whether there was enough evidence to make such a recommendation.

“There is not currently enough information on ibuprofen use and COVID-19 to advise people to stop using NSAIDs. There is currently no published scientific evidence that ibuprofen increases the risk of catching COVID-19 or makes the illness worse. In addition, there is also no conclusive evidence that taking ibuprofen is harmful for other respiratory infections,” the RPS said in a statement.

The Medical University of Vienna also chimed in, calling reports that it had found a connection between ibuprofen use and worse coronavirus symptoms "fake news."

But other experts agreed that NSAIDs can weaken the immune system.

“Despite all of their beneficial effects, it has long been known that anti-inflammatories can have a depressive effect on parts of our immune systems,” Dr. Amir Khan of Britain’s National Health Service said in Al Jazeera. “If we take medicines that dampen this immune response, such as ibuprofen, this can lead to us not fighting off the infection as effectively, potentially leading to a longer illness with a higher risk of complications.

“Paracetamol is not an anti-inflammatory medication and can be used to effectively treat fever as well as mild to moderate pain and can, therefore, be used safely to help treat the fever associated with the coronavirus.”

The NHS also updated its recommendations, cautioning that while there is no strong evidence that ibuprofen makes coronavirus worse, “until we have more information, take paracetamol to treat the symptoms of coronavirus.”

‘Don’t Give Her Ibuprofen!’

The New York Post reported that a 4-year old British girl suffering coronavirus symptoms had difficulty breathing and took a turn for the worse after taking ibuprofen. Amelia Collins had a cough, fever and other flu-like symptoms.

“To those of you that have children please read. If your child has symptoms of corona virus, DO NOT give them ibuprofen,” Amelia’s father posted on Facebook. “Within an hour of giving her [ibuprofen] she dropped dramatically. She was panting while trying to breathe, her heart rate was very rapid, she couldn’t keep her eyes open, couldn’t lift her head up, her body was shaking, she started being sick on herself and her temperature had risen.”

Amelia’s parents called for an ambulance. Fortunately, paramedics were able reduce her fever without taking her to a hospital.

“Now she’s back on [acetaminophen] she’s back to just being her poorly self. The paramedics only told us while here that were not to give her ibuprofen!” the father said.

In 2015, the U.S. Food and Drug Administration warned that “everyone may be at risk” and ordered new warning labels for ibuprofen and other NSAIDs to indicate they increase the risk of a fatal heart attack or stroke.

But acetaminophen also has issues. The pain reliever has long been associated with liver injury and allergic reactions such as skin rash. Acetaminophen is the active ingredient in hundreds of over-the-counter pain relievers and cough, cold and flu medicines – and many consumers have no idea how much acetaminophen they’re taking.

Over 50,000 emergency room visits each year in the U.S. are blamed on acetaminophen overdoses, including 25,000 hospitalizations and hundreds of deaths.

Avoiding Coronavirus: Lessons Learned From People With Weak Immune Systems

By Anna Maria Barry-Jeter, Kaiser Health News

Andrea Amelse knows hand-washing.

For the past eight years, she’s been washing her hands pretty much every time she passes a sink. When she’s near a bottle of antibacterial gel, she uses it. She makes a point of avoiding people with contagious illnesses, even though it can be uncomfortable to ask to work from home or miss a date with friends. And she makes sure she gets plenty of sleep, not always easy at age 25.

Amelse was diagnosed in 2012 with lupus, an autoimmune disease that makes her vulnerable to infections. She’s since developed pulmonary arterial hypertension, a condition that requires intravenous therapy via a central line to her heart. Both illnesses place her at heightened risk for viral and bacterial illnesses. So, she has adapted as a matter of survival, taking to heart long-standing axioms on what constitutes good hygiene.

As the highly contagious new coronavirus continues its spread through the U.S., the general public could learn a thing or two from Amelse and the millions of other Americans with weakened immune systems who already live by rules of infection control.

Whether it’s people who had recent organ transplants, people undergoing chemotherapy or people with chronic diseases, America has a broad community of immunosuppressed residents who long ago adopted the lifestyle changes public officials now tout as a means of avoiding contagion: Wash your hands, and wash them often. Don’t touch your face. Avoid that handshake. Keep your distance from people who cough and sneeze.

Amelse doesn’t follow the advice perfectly — of course she touches her face sometimes.

“You do these things unknowingly, so forcing yourself to break these habits can be challenging,” she said. But the incentive to keep getting better is there. “If you get a cold and you give me that same cold, you might get it for a week. I’ll get it for a month.”

Even with her dedication, COVID-19 is proving a daunting prospect to face. And she has a stake in Americans adopting these habits because, while the disease is relatively minor for many people who get it, it can be life-threatening for people with preexisting conditions.

Amelse works at a health literacy startup in Minneapolis that helps patients with complicated diseases learn about their illness. She knows a lot about health and how to prevent infection. Still, the threat of COVID-19 is unnerving, for her and her doctors.

Stockpile Essential Supplies

With a virus so new, official guidance on what people at heightened risk should do to steer clear of COVID-19 is limited. But the Centers for Disease Control and Prevention recently said the virus seems to hit hardest in people 60 and older with underlying health concerns. There is also concern for younger people with limited immune systems or complex diseases.

Health officials are asking those at risk to stockpile two-week supplies of essential groceries and medicines in case they need to shelter at home; to avoid crowds and heavily trafficked areas; to defer nonessential travel; and to track what’s going on in their community, so they know how strictly to follow this advice.

Infection control always follows a similar set of principles, said Dr. Jay Fishman, director of the Transplant Infectious Disease and Compromised Host Program at Massachusetts General Hospital and a professor at Harvard Medical School. The most important things for people to do right now are the things he always recommends to his organ transplant and cancer patients. Again, think hand-washing and avoiding spaces where sick people congregate.

Still, the recommendations aren’t one-size-fits-all. Some people are born with stronger immune systems, and immune deficits exist on a spectrum, said Fishman. How strict people need to be to prevent illness can vary depending on how susceptible they are.

Avoid Crowds

Recommendations also need to take into account what people can and will do, he said. Children, for example, are among the greatest germ vectors of all time, but Fishman doesn’t ask his patients with grandchildren to stay away from their young family members. “We did the transplant so you can see your grandchildren,” he might tell them.

Similarly, avoiding crowds and staying away from sick people is easy for some but can be all but impossible if you work in food service, for example. Find ways to avoid the risks and reduce them where possible.

Though there isn’t great research on how well transplant patients and others manage to prevent infection, Fishman said many of his patients don’t get sick any more frequently than the general population, despite their vulnerabilities. But when they do, the illnesses tend to last longer, be more severe and put people at higher risk for additional infections. He counsels patients to be vigilant, but also to live their lives and not be ruled by fear.

Dr. Deborah Adey, a transplant nephrologist for UCSF Health, echoed Fishman, saying she likes to find ways to help her patients carry on with their lives. A patient recently asked if it was OK to fly to Salt Lake City, and she suggested they drive instead.

Gauging the risks can be tough. Amelse was relieved when a major health conference she was scheduled to attend recently in Florida was canceled at the last minute. She wasn’t sure it was safe to travel, but it also was unclear how to categorize an important work trip: Was this essential? Nonessential?

Adey conducts follow-up appointments via teleconferencing where possible, to keep her patients out of medical facilities. Hospitals are, by design, places for the sick, and people with compromised immune systems are generally advised to avoid them and the viruses and bacteria potentially inside.

That matches advice from officials in California and other states, asking people to stay out of emergency rooms unless absolutely necessary. They are asking people, when possible, to call ahead to their doctors and stay home unless an illness is serious.

Good Hygiene

And, similar to what public officials are advising the general population, Adey does not recommend that her patients wear face masks when out in public or even at the clinic. “The only people I would recommend is if they’ve got a lot of close contact with the general public, and they can’t afford to be off work.”

While much has been made of the hoarding sprees for face masks, the empty hand sanitizer shelves are equally frustrating for Amelse. Every 48 hours, she has to mix and administer drugs she places in an IV that goes into her heart. Everything must be sanitized, and she typically gets monthly shipments of antibacterial wipes and sanitizer. If suppliers run out, she’s worried she’ll have to go to a hospital to have the drugs administered — exactly where her doctors don’t want her to be.

Officials are desperately working on a vaccine for the coronavirus for use in as little as 12 to 18 months. But many vaccines are made from live viruses and can’t be given to some immunosuppressed people.

Given the risk COVID-19 poses for people with compromised immune systems, the government needs to stress how important it is for everyone to follow good hygiene protocols, said Fishman. “The worst thing we can do is downplay it.”

And for those just getting up to speed on preventing infections, Amelse has advice: “Viruses don’t pick and choose; they will latch on anywhere,” she said. Even if it’s not a serious illness for you, “there are people in your life that you can infect. You have the obligation and the responsibility to take care of your loved ones.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente. This story was first published on California Healthline, a service of the California Health Care Foundation.

Chronic Pain Changes Our Immune Systems

By Pat Anson, Editor

Scientists already know that chronic pain can change the way our brains work, but now there is new evidence that pain may also make lasting changes in our immune systems.

In studies on laboratory rats, researchers at McGill University in Montreal found that chronic pain alters the way genes work in the immune system. The discovery may help explain why pain can persist long after the initial injury.

"We found that chronic pain changes the way DNA is marked not only in the brain but also in T cells, a type of white blood cell essential for immunity,” said Moshe Szyf, a professor in the Faculty of Medicine at McGill. "Our findings highlight the devastating impact of chronic pain on other important parts of the body such as the immune system."

McGill researchers examined DNA from the brains and white blood cells of rats nine months after a nerve injury. They found a “stunning” number of changes in DNA methylation – which regulates how genes function. Chronic pain appeared to reprogram how the genes work.

"We were surprised by the sheer number of genes that were marked by the chronic pain -- hundreds to thousands of different genes were changed," adds Szyf. "We can now consider the implications that chronic pain might have on other systems in the body that we don't normally associate with pain."

Many of the genes that were altered are associated with depression, anxiety, and loss of cognition, which are some of the negative side effects of chronic pain.  The findings could open new avenues to diagnosing and treating chronic pain in humans, as some of the genes affected by chronic pain could represent new targets for pain medications.

“These findings reveal potential new avenues for the development of novel therapeutics directed at either the molecular regulation of methylation or at key genes or pathways dysregulated in chronic pain,” the study found.  “This work also provides a possible mechanistic explanation for commonly observed comorbidities observed in chronic pain (i.e anxiety, depression). Finally, the sheer magnitude of the impact of chronic pain, particularly in the prefrontal cortex, illustrates the profound impact that living with chronic pain exerts on an individual.”

The McGill study is published in the journal Scientific Reports.

A recent study at Northwestern University found that chronic pain “rewires” a part of the brain that controls whether we feel happy or sad.  Researchers found that a group of neurons thought to be responsible for negative emotions became hyper-excitable within days of an injury that triggers chronic pain.