In the Blood: Which Antibodies Best Neutralize the Coronavirus In COVID-19 Patients?

Blood tests to detect antibodies against SARS-CoV-2, the virus that causes COVID-19, are an important tool for diagnosing the disease, developing potential treatments, and checking vaccine efficacy. Although such tests are available, we have very little understanding on how different antibodies interact with virus antigens. Scientists from Fujita Health University set out to assess various antigen-specific antibodies and determined which of them had the strongest neutralizing activity against SARS-CoV-2.

The COVID-19 pandemic has now claimed over 2 million deaths worldwide, and this number is only increasing. In response, health agencies have rolled out tests to diagnose and understand the disease. Besides the now widely known PCR test, there is interest in serological (blood) tests that detect “antibodies” against SARS-CoV-2, the virus that causes COVID-19. These blood tests have considerable applications, from identifying blood donors with high levels of anti-SARS-CoV-2 antibodies, whose blood can be used for convalescent plasma therapy, to measuring vaccine effectiveness.

So, what are antibodies? These are proteins produced by the body’s immune system to combat foreign proteins, such as the SARS-CoV-2 virus. Antibodies function by binding to a specific part of the virus that the immune system recognizes, called “antigens.” SARS-CoV-2 is composed of four major proteins, with two being highly immunogenic (capable of producing an immune response). These immunogenic proteins are called spike (S) and nucleocapsid (N) proteins. Presence of antibodies specific to the S protein means there is a higher amount of virus-neutralizing activity while antibodies specific to N protein indicate the presence of previous SARS-CoV-2 infection.

Despite this general awareness, we actually have only a vague understanding of how different antibodies (or antibody “isotypes”) interact with the various antigens produced by SARS-CoV-2. Hence, a team of scientists led by Senior Assistant Professor Hidetsugu Fujigaki and Professor Yohei Doi from Fujita Health University, in collaboration with National Institute of Infectious Diseases, Japan, FUJIFILM Wako Pure Chemical Corporation, and FUJIFILM Corporation undertook the first detailed investigation of these interactions. “Our goal was to quantify the neutralizing activity of these different antibodies against SARS-CoV-2,” Dr. Fujigaki explains, “We looked at antibodies specific to different parts of the S protein and the N protein to determine which of them was the best predictor of stopping the virus.”

They did this through an analysis of blood samples from 41 COVID-19 patients at the Fujita Health University Hospital. The team developed assays using three common antibodies (IgG, IgM, and IgA), each of them split into isotypes that bind specifically to five antigens (three parts of the S protein, including the receptor binding domain [RBD], the full S protein, and the full N protein).

The results of their experiments showed that all antibody isotypes that bind to the S protein (full and parts) were highly specific, but antibody isotypes binding to the N protein were less so. With minor variations, all antibodies are detectable in patients at approximately 2 weeks after symptoms appear, and detection sensitivity was higher than 90% (except in the case of IgM binding to N protein). Importantly, the researchers showed that IgG specific to the RBD of S protein had the highest correlation with virus neutralizing activity and disease severity. In other words, measuring RBD-specific IgG levels could tell us a lot about the immune response of COVID-19 patients, and could be the foundation for improving COVID-19 blood tests.

“We are also very excited by our findings because of their implications for convalescent serum/plasma therapy, a type of treatment where you transfuse blood from people who recovered from COVID and have high levels of antibodies against SARS-CoV-2,” Dr. Fujigaki adds, “Being able to show that the IgG antibody against RBD is highly correlated with neutralizing activity means we can identify appropriate blood donors for this treatment.”

The world is hopefully moving into the final stages of the pandemic, and this information could be the tools needed to carve out the final few steps to a safe post-pandemic world.

Source: Fujita Health University

World-first Study on Blood Hormone could Reduce Cardiovascular Deaths

Kim Thomas wrote . . . . . . . . .

A simple blood test could identify seemingly-healthy people with a high hidden risk of heart disease thanks to a world-first discovery by University of Otago, Christchurch researchers.

Researchers from the University’s Christchurch Heart Institute studied the blood samples and cardiology scans of 665 healthy young and middle-aged people with no previous heart conditions. They found people with high levels of a hormone in the blood, called C-type Natriuretic Peptide (CNP), were significantly more likely to have stiffening of the arteries, reduced pumping action of the heart, higher fat levels in the blood and liver, and reduced kidney function—all signs of increased risk of heart disease.

The discovery could one day enable doctors to identify those people whose lives could be saved from a future heart attack by interventions such as drugs or lifestyle changes.

The study is the first to describe a link between the blood hormone CNP and inflammation across a range of tissues including arteries and the heart. The results were recently published in the prestigious Peptides journal.

Lead researcher Dr. Tim Prickett says CNP seems to protect arteries from hardening and blocking. This means it is working hard and present in higher levels in those with potentially poor, and undetected, cardiovascular health.

“We examined two quite different groups of healthy people—one group age 28 years, the other age 50 years—both without history of heart or kidney disease. High levels of CNP in both age groups were found in people who had stiffer arteries, reduced pumping action of the heart, higher fat levels in the blood and liver, and reduced kidney function.”

Dr. Prickett says inflamed and blocked arteries can cause numerous physical problems including scarring and stiffness and damage to organs such as the heart, liver and kidneys. “We found that CNP in the blood stream reflects an increased production of CNP in these tissues, as part of a protective response to inflammation.”

He says the finding that CNP acts to protect the body is key to helping save lives through early detection of serious conditions such as atherosclerosis, which can lead to heart attack or stroke.

This is one of a number of discoveries by the Christchurch Heart Institute over the past 25 years. The research group has discovered and developed blood tests for heart disease diagnosis and treatment, some of which are used in hospitals and emergency departments in New Zealand and around the globe.

Source: Medical Xpress


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Higher End of Normal Blood Platelet Count Could Indicate Cancer

Blood platelet counts at the higher end of normal suggest a high risk of cancer in men aged 60 or over, and should be investigated, according to new University of Exeter research.

Platelets perform a crucial function in blood, including helping blood to clot, which helps us heal wounds. However, Exeter researchers have previously found that cancer risk is significantly raised by having an abnormally high blood platelet count (more than 400 x 109/l,) a condition known as thrombocytosis. Now, they have found that cases of cancer greatly increased in older males with a platelet count on the high end of normal range (326 to 400 x 109/l), indicating that these patients should be investigated for cancer.

In a study funded by NIHR and published in the British Journal of General Practice, researchers reviewed the records of nearly 300,000 patients who had platelet counts on the higher end using data from the Clinical Practice Research Datalink and the National Cancer Registration and Analysis Service. They found that the number of these patients diagnosed with cancer a year later was significantly higher if the patients had even slightly raised platelet levels. Of 68,181 male patients with levels of blood platelet on the higher end of normal, 1,869 cases of cancer were diagnosed within one year. Of these, 720 were an advanced stage. A higher platelet count was most frequently linked to lung and colorectal cancers – both aggressive forms of cancer.

Dr Sarah Bailey, Senior Research Fellow at the University of Exeter Medical School who led the research, said: “After finding that having a blood platelet count above normal range put people at high risk of cancer, we investigated the risk at the high end of normal. We found that men aged over 60 whose platelet count is on higher end of a normal are more likely to have an underlying cancer. Updating guidance for GPs to investigate higher platelet counts could save lives. This is particularly important in a post-COVID era; clues to help GPs identify cancer earlier are crucial to target the backlog in cancer investigation and diagnosis” Professor Willie Hamilton, of the University of Exeter Medical School, said: “The UK lags well behind other developed countries on early cancer diagnosis. Our findings on platelet count and cancer diagnosis can help to combat that lag. It is now crucial that we roll out cancer investigation of thrombocytosis. It could save hundreds of lives.”

Source: University of Exeter


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Pulse Pressure: A Game Changer in the Fight Against Dementia

A recent paper published in Frontiers in Neuroscience, outlines a pulse-pressure-induced pathway of cognitive decline that sheds light on why previous treatments for dementia may have failed and proposes promising new directions for the prevention and treatment of dementia.

“Over the last couple years, a sea change in dementia and Alzheimer’s disease research has occurred. Focus has shifted from solely targeting amyloid-beta in the brain to the opinion that more fruitful progress could be made by addressing factors that compromise the blood brain barrier,” explains co-author Mark Carnegie, of The Brain Protection Company based in Australia. “Elements of the constellation include chronic age-related inflammation, genetic predisposition, and cardiovascular abnormalities, notably high blood pulse pressure.”

Connecting a large and rapidly growing body of evidence, the researchers elucidate how elevated pulse pressure may cause dementia. Pulse pressure is the difference between systolic and diastolic blood pressure and commonly increases with age.

The researchers propose that elevated pulse pressure in blood travelling to the brain can cause inflammation, oxidative stress, mechanical stress, cellular dysfunction, and cell death in the blood brain barrier that leads to brain damage.

The link between blood brain barrier breakdown and dementia is intuitive, as the blood brain barrier has specifically evolved to support and protect delicate brain tissue by keeping circulating cells, pathogens, and other unhealthy substances in blood from infiltrating the brain. There is significant evidence supporting that disruption of the blood brain barrier is a key driver of cognitive decline and dementia.

Senior author of the paper, Prof. David Celermajer of The Brain Protection Company, says that “this is an important paradigm shift in our understanding of the pathogenesis of dementia.”

He further adds that “although there are likely several causes of blood brain barrier disruption, recent human cell culture experiments, animal models, and epidemiological evidence have pointed to high blood pulse pressure as one potential key cause.”

Pulse pressure may therefore be a promising new therapeutic target for preventing or slowing cognitive impairment, which gives new hope in the fight against dementia.

Moreover, the authors discuss how elevated pulse pressure may have also prevented previous treatment strategies from working optimally against dementia.

For the past two decades, a primary focus of drug development for Alzheimer’s disease, the most prevalent form of dementia, has been to target the molecule amyloid-beta. However, despite billions of dollars spent on R&D, that approach has yet to be successful.

The researchers suggest that targeting amyloid-beta alone to treat dementia may be an uphill battle since concurrent elevated pulse pressure will continue to activate secretion of various inflammatory and oxidative molecules and amyloid-beta from the blood brain barrier into brain tissue.

Also, stem and progenitor cell therapies have gained significant attention as potential strategies to repair blood brain barrier damage and treat dementia, but chronic inflammatory and oxidative stress due to elevated pulse pressure can impact the health of stem and progenitor cells.

Dr. Rachel Levin, lead author of the paper, says that “combination therapy has been paramount in the treatment of other challenging diseases, in particular cancer. Therefore, in dementia, reducing elevated pulse pressure could prove to be synergistic with other therapeutic approaches such as anti-amyloid-beta drugs or stem cell therapy.”

The authors issue a call to action for academic and industry leaders to develop novel drug candidates or devices that reduce elevated pulse pressure and progress them to clinical trials. Celermajer states that “strong animal model data already supports the role of high pulse pressure in blood brain barrier disruption and dementia pathology; now more human studies are needed.”

Source: EurekAlert!


Read the paper at Frontiers in Nuroscience . . . . .


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Study: Blood Count May Offer Clues to Treatment of COVID-19

The severity of COVID-19 illness may be influenced by what researchers call “cytokine storms.”

In a new study, investigators assessed 522 COVID-19 patients, aged 5 days to 97 years, who were admitted to two hospitals in Wuhan, China, in December and January. The study also included a “control group” of 40 healthy people.

Compared to the control group, 76% of COVID-19 patients had significantly lower levels of T cells — a type of white blood cell that plays a crucial role in immune response against viral infections.

Patients admitted to the intensive care unit had much lower T cell counts than those who didn’t require ICU care. Patients over age 60 had the lowest T cell counts, the findings showed.

And the T cells that did survive in COVID-19 patients were exhausted and unable to function at full capacity, the study authors said.

COVID-19 patients also had high levels of cytokines — a protein that normally helps fight off infection. Too many cytokines can prompt an excessive inflammatory response called a “cytokine storm,” which causes the proteins to attack healthy cells.

That suggests the new coronavirus does not attack T cells directly. Instead, it triggers the cytokine release, which results in the loss and exhaustion of T cells, according to the authors of the study published May 1 in the journal Frontiers in Immunology.

The study results provide new clues on how to treat COVID-19, the researchers said.

“We should pay more attention to T cell counts and their function, rather than respiratory function of patients,” study author Dr. Yongwen Chen of Third Military Medical University in Chongqing, China, said in a journal news release.

Chen added that “more urgent, early intervention may be required in patients with low T lymphocyte counts.”

In addition, he noted, future research should focus on pinpointing subgroups of T cells that may be most important in COVID-19, along with identifying drugs that boost T cell counts and functioning.

Source: HealthDay