Neutralizing antibodies isolated from COVID-19 patients may suppress virus
Date: July 22, 2020
Source:Columbia University Irving Medical Center
Summary:Researchers have isolated antibodies from several COVID-19 patients that, to date, are among the most potent in neutralizing the SARS-CoV-2 virus. These antibodies could be produced in large quantities by pharmaceutical companies to treat patients, especially early in the course of infection, and to prevent infection, particularly in the elderly.Share:
FULL STORY Researchers at Columbia University Irving Medical Center have isolated antibodies from several COVID-19 patients that, to date, are among the most potent in neutralizing the SARS-CoV-2 virus. These antibodies could be produced in large quantities by pharmaceutical companies to treat patients, especially early in the course of infection, and to prevent infection, particularly in the elderly. "We now have a collection of antibodies that's more potent and diverse compared to other antibodies that have been found so far, and they are ready to be developed into treatments," says David Ho, MD, scientific director of the Aaron Diamond AIDS Research Center and professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, who directed the work. The researchers have confirmed that their purified, strongly neutralizing antibodies provide significant protection from SARS-CoV-2 infection in hamsters, and they are planning further studies in other animals and people. Why look for neutralizing antibodies One of the human body's major responses to an infection is to produce antibodies -- proteins that bind to the invading pathogen to neutralize it and mark it for destruction by cells of the immune system.
Though a number of drugs and vaccines in development for COVID-19 are in clinical trials, they may not be ready for several months. In the interim, SARS-CoV-2 neutralizing antibodies produced by COVID-19 patients could be used to treat other patients or even prevent infection in people exposed to the virus. The development and approval of antibodies for use as a treatment usually takes less time than conventional drugs. This approach is similar to the use of convalescent serum from COVID-19 patients, but potentially more effective. Convalescent serum contains a variety of antibodies, but because each patient has a different immune response, the antibody-rich plasma used to treat one patient may be vastly different from the plasma given to another, with varying concentrations and strengths of neutralizing antibodies. Sicker patients produce more potent antibodies When SARS-CoV-2 arrived and led to a pandemic at the beginning of the year, Ho rapidly shifted the focus of his HIV/AIDS laboratory to work on the new virus. "Most of my team members pretty much have been working nonstop 24/7 since early March," says Ho. The researchers had easy access to blood samples from patients with moderate and severe disease who were treated at Columbia University Irving Medical Center in New York City, the epicenter of the pandemic earlier this year. "There was plenty of clinical material, and that allowed us to select the best cases from which to isolate these antibodies," Ho says.
Ho's team found that although many patients infected with SARS-CoV-2 produce significant quantities of antibodies, the quality of those antibodies varies. In the patients they studied, those with severe disease requiring mechanical ventilation produced the most potently neutralizing antibodies. "We think that the sicker patients saw more virus and for a longer period of time, which allowed their immune system to mount a more robust response," Ho says. "This is similar to what we have learned from the HIV experience." Antibody cocktails The majority of anti-SARS-CoV-2 antibodies bind to the spike glycoprotein -- a feature that gives the virus its corona -- on the virus's surface. Some of the most potent antibodies were directed to the receptor binding domain (where the virus attaches to human cells), but others were directed to the N-terminal region of the spike protein. The Columbia team found a more diverse variety of antibodies than previous efforts, including new, unique antibodies that were not reported earlier. "These findings show which sites on the viral spike are most vulnerable," Ho says. "Using a cocktail of different antibodies that are directed to different sites in spike will help prevent the virus becoming resistant to the treatment." Implications for vaccines "We discovered that these powerful antibodies are not too difficult for the immune system to generate. This bodes well for vaccine development," Ho says. "Vaccines that elicit strong neutralizing antibodies should provide robust protection against the virus." Antibodies may also be useful even after a vaccine is available. For example, a vaccine may not work well in the elderly, in which case the antibodies could play a key role in protection. Implications for immunity This research demonstrates that people with severe disease are more likely to have a durable antibody response, however more research needs to be done to answer the critical question about how long immunity to COVID-19 will last. What's next The researchers are now designing experiments to test the strategy in other animals, and eventually in humans. If the animal results hold true in humans, the pure, highly neutralizing antibodies could be given to patients with COVID-19 to help them clear the virus. Caveats Although tremendously informative for researchers developing vaccines and antiviral therapies, the findings are early-stage preclinical results and the antibodies are not yet ready for use in people. David Ho is the Clyde '56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and scientific director and chief executive officer of the Aaron Diamond AIDS Research Center. The new paper appears in the journal Nature. This study was supported by grants from the Jack Ma Foundation, the JPB Foundation, the NIH (U24 GM129539), the Simons Foundation (SF349247), and the New York State Assembly. Story Source: Materials provided by Columbia University Irving Medical Center. Note: Content may be edited for style and length. Journal Reference:
Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro, David D. Ho. Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature, 2020; DOI: 10.1038/s41586-020-2571-7
Columbia University Irving Medical Center. "Neutralizing antibodies isolated from COVID-19 patients may suppress virus." ScienceDaily. ScienceDaily, 22 July 2020. <www.sciencedaily.com/releases/2020/07/200722083804.htm>.
Common blood test identifies benefits and risks of steroid treatment in COVID-19 patients
Date:July 22, 2020
Source:Albert Einstein College of Medicine
Summary:A new study confirms the findings of the large scale British trial of steroid use for COVID-19 patients and advances the research by answering several key questions: Which patients are most likely to benefit from steroid therapy? Could some of them be harmed? Can other formulations of steroids substitute for the agent studied in the British trial?Share:
FULL STORY A new study led by Albert Einstein College of Medicine and Montefiore Health System confirms the findings of the large scale British trial of steroid use for COVID-19 patients and advances the research by answering several key questions: Which patients are most likely to benefit from steroid therapy? Could some of them be harmed? Can other formulations of steroids substitute for the agent studied in the British trial? The research was published today in the Journal of Hospital Medicine.
The U.K. RECOVERY trial, a prospective, randomized, open-label study of the steroid dexamethasone versus standard of care, involved more than 6,000 patients with COVID-19. Dexamethasone reduced deaths by about one-third in patients on ventilators and by about one-fifth among people who needed oxygen but were not on ventilators. However, the study leaves questions about the use of steroids for treating some patients. "Our study is consistent with the promising findings from Britain, but for the first time, we are able to demonstrate that people can see the same life-saving benefits with steroid formulations other than dexamethasone," said Marla Keller, M.D., vice chair for research in the department of medicine at Einstein and Montefiore and lead author of the study. "We also found that a common blood test may identify the best candidates for steroid treatment." Dr. Keller is also professor of medicine and of obstetrics & gynecology and women's health at Einstein and an infectious disease specialist at Montefiore. Authors of the Einstein-Montefiore study compared outcomes for two groups selected from nearly 3,000 people hospitalized at Montefiore with a positive COVID-19 test. One group of 140 patients was treated with steroids within 48 hours of hospital admission; and a control group of 1,666 similar patients did not receive steroid therapy. Most of the patients who received steroid therapy received prednisone. Some received dexamethasone and methylprednisolone.
Nearly all patients initially had a blood test to measure levels of C-reactive protein (CRP), which the liver produces in response to inflammation. The higher the CRP level in the blood, the greater amount of inflammation. A normal CRP level reported in the study is below 0.8 milligrams per deciliter of blood.
"We found that in patients with high levels of inflammation, namely a CRP level greater than 20, steroids were associated with a 75% reduction in the risk of going on mechanical ventilation or dying," said Dr. Keller. "Critically, we also found that for patients with a normal or low level of inflammation, CRP levels less than 10, steroid use was associated with an almost 200% increased risk of going on mechanical ventilation or death." A large percent of the people who succumb to COVID-19 die from the body's intense inflammatory response, which can overwhelm and severely damage the lungs. "Our findings suggest that steroid therapy should be reserved for people with high inflammation, as indicated by markedly elevated CRP levels," said William Southern, M.D., M.S., professor of medicine and chief of the division of hospital medicine at Einstein and Montefiore and the study's senior author. "It's a different story for people who do not have significant inflammation: for them, any benefit is outweighed by the risks from using steroids."
Study co-author Shitij Arora, M.D., associate professor of medicine at Einstein and a hospitalist at Montefiore, noted that the Einstein-Montefiore study included approximately equal numbers of male and female patients. In addition, nearly 40% of patients studied were Black and 36% were Hispanic. "The demographic diversity of the patients in this study suggests that steroid therapy benefits hospitalized COVID-19 patients affected by significant inflammation regardless of their race or ethnicity," he said. The title of this paper is "Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19." Other Einstein and Montefiore authors were Jen-Ting Chen, M.D., M.S., Elizabeth Kitsis, M.D., M.B.E., Shivani Agarwal, M.D., M.P.H., Michael Ross, M.D., and Yaron Tomer, M.D. make a difference: sponsored opportunity Story Source: Materials provided by Albert Einstein College of Medicine. Note: Content may be edited for style and length. Journal Reference:
Marla J Keller, Elizabeth A Kitsis, Shitij Arora, Jen-Ting Chen, Shivani Agarwal, Michael J Ross, Yaron Tomer, William Southern. Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19. Journal of Hospital Medicine, 2020; (2020-07-22 ONLINE FIRST) DOI: 10.12788/jhm.3497
Albert Einstein College of Medicine. "Common blood test identifies benefits and risks of steroid treatment in COVID-19 patients." ScienceDaily. ScienceDaily, 22 July 2020. <www.sciencedaily.com/releases/2020/07/200722083809.htm>.
Coronavirus antibodies fall dramatically in first 3 months after mild cases of COVID-19
Date:July 22, 2020
Source:University of California - Los Angeles Health Sciences
Summary:In people with mild cases of COVID-19, antibodies against SARS-CoV-2 -- the virus that causes the disease -- drop sharply over the first three months after infection, decreasing by roughly half every 36 days, a new study finds. If sustained at that rate, the antibodies would disappear within about a year.Share:
FULL STORY A study by UCLA researchers shows that in people with mild cases of COVID-19, antibodies against SARS-CoV-2 -- the virus that causes the disease -- drop sharply over the first three months after infection, decreasing by roughly half every 36 days. If sustained at that rate, the antibodies would disappear within about a year.
Previous reports have suggested that antibodies against the novel coronavirus are short-lived, but the rate at which they decrease has not been carefully defined. This is the first study to carefully estimate the rate at which the antibodies disappear.
The researchers studied 20 women and 14 men who recovered from mild cases of COVID-19. Antibody tests were conducted at an average of 36 days and 82 days after the initial symptoms of infection.
The findings raise concerns about antibody-based "immunity passports," the potential for herd immunity and the reliability of antibody tests for estimating past infections. In addition, the findings may have implications for the durability of antibody-based vaccines.
Authors of the study are F. Javier Ibarrondo, Dr. Jennifer Fulcher, Dr. David Goodman-Meza, Julie Elliott, Christian Hofmann, Mary Hausner, Kathie Ferbas, Dr. Nicole Tobin, Dr. Grace Aldrovandi and Dr Otto Yang, all of UCLA.
The research is published in the peer-reviewed New England Journal of Medicine. The AIDS Healthcare Foundation, the Doris Duke Charitable Foundation, the National Institutes of Health, the James B. Pendleton Charitable Trust and the McCarthy Family Foundation funded the study. make a difference: sponsored opportunity Story Source: Materials provided by University of California - Los Angeles Health Sciences. Note: Content may be edited for style and length. Journal Reference:
F. Javier Ibarrondo, Jennifer A. Fulcher, David Goodman-Meza, Julie Elliott, Christian Hofmann, Mary A. Hausner, Kathie G. Ferbas, Nicole H. Tobin, Grace M. Aldrovandi, Otto O. Yang. Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19. New England Journal of Medicine, 2020; DOI: 10.1056/NEJMc2025179
We are mutating SARS-CoV-2, but it is evolving back
Date:July 22, 2020
Source:University of Bath
Summary:Scientists looked at the evolution of the virus that causes COVID-19. Their findings could help the design of a new vaccine.Share:
FULL STORY Scientists investigating the evolution of the virus that causes COVID-19 say that its mutation seems to be directed by human proteins that degrade it, but natural selection of the virus enables it to bounce back. The findings could help in the design of vaccines against the virus.
All organisms mutate. You were for example born with between 10 and 100 new mutations in your DNA. Mutation is usually a random process often owing to mistakes made when DNA is copied. Recent work from researchers at the Universities of Bath and Edinburgh, suggests that in the case of SARS-CoV-2, mutation may well not be a random process and that instead humans are mutating it, as part of a defence mechanism to degrade the virus.
The team looked at over 15,000 virus genomes from all of the sequencing efforts around the world and identified over 6000 mutations. They looked at how much each of the four letters that make up the virus' genetic code (A, C, U and G) were mutating and discovered that the virus had a very high rate of mutations generating U residues. Senior author Professor Laurence Hurst, Director of the Milner Centre for Evolution at the University of Bath, said: "I have looked at mutational profiles for many organisms and they all show some sort of bias, but I've never seen one as strong and strange as this." In particular they found that mutation very commonly generated UU neighbouring pairs, mutating from the original sequence of CU and UC. They noted this is a fingerprint of the mutational profile of a human protein, called APOBEC, that can mutate viruses. Professor Hurst commented: "It looks like mutation isn't random, but instead we are attacking the virus by mutating it."
But what are these mutations doing to the virus? Are they helping or hindering it? Looking at the actual composition of the virus and by comparing between different sorts of sites within the virus they found evidence that natural selection -- survival of the fittest -- is allowing the virus to fight back against the mutational process. From the mutational profile the team predicts, for example, that 65% of the residues should be a U and 40% should be UU pairs, but in practice U content is much lower and UU content is just about a quarter of that predicted.
Professor Hurst said: "This could be because the viruses that have too much U in them simply don't survive well enough to reproduce. We estimate that for every 10 mutations that we see, there are another six we never get to see because those mutant viruses are too poor at propagating."
And there are several reasons why this might be. U rich versions of the viruses' genes the team found to be less stable and are seen at lower levels. Humans also have other proteins that attack sequences that are rich in U residues that might also force destruction of some versions of the virus.
These results suggest that we are attacking the virus to mutate it in a manner that degrades the virus. This also has implications for some vaccine designs. Several research groups are currently trying to make synthetic versions of the virus in a manner that enables the virus to be viable, but only just, so called attenuated viruses. Professor Hurst said: "Knowing what selection favours and disfavours in the virus is really helpful in understanding what an attenuated version should look like. "We suggest for example that increasing U content, as APOBEC does within our cells, would be a sensible strategy." Story Source: Materials provided by University of Bath. Note: Content may be edited for style and length. Journal Reference:
Alan M Rice, Atahualpa Castillo Morales, Alexander T Ho, Christine Mordstein, Stefanie Mühlhausen, Samir Watson, Laura Cano, Bethan Young, Grzegorz Kudla, Laurence D Hurst. Evidence for strong mutation bias towards, and selection against, U content in SARS-CoV-2: implications for vaccine design. Molecular Biology and Evolution, 2020; DOI: 10.1093/molbev/msaa188
University of Bath. "We are mutating SARS-CoV-2, but it is evolving back." ScienceDaily. ScienceDaily, 22 July 2020. <www.sciencedaily.com/releases/2020/07/200722163242.htm>.
Lung ultrasound shows duration, severity of coronavirus disease (COVID-19)
Date:July 23, 2020
Source:American Roentgen Ray Society
Summary:A new study found that lung ultrasound was highly sensitive for detecting abnormalities in patients with coronavirus disease (COVID-19), with B-lines, a thickened pleural line, and pulmonary consolidation the most commonly observed features. Additionally, the authors found that lung ultrasound features can be used to reflect both the infection duration and disease severity.Share:
FULL STORY According to an open-access article published in ARRS' American Journal of Roentgenology (AJR), lung ultrasound (US) was highly sensitive for detecting abnormalities in patients with coronavirus disease (COVID-19), with B-lines, a thickened pleural line, and pulmonary consolidation the most commonly observed features. "In addition," concluded Yao Zhang of at China's Beijing Ditan Hospital, "our results indicate that lung US findings can be used to reflect both the infection duration and disease severity."
From March 3 to March 30, 2020, Zhang and colleagues performed lung US on consecutive patients with positive reverse transcriptase polymerase chain reaction (RTPCR) test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the Fisher exact test to compare the percentages of patients with each US finding between groups with different symptom durations and disease severity.
All 28 patients (14 men and 14 women; age range, 21-92 years) had positive findings on both lung US and chest CT. On US, B-lines were present in 100% of patients, and 19 (67.9%) patients had pulmonary consolidation. Thickened pleural lines were observed in 17 patients (60.7%), and only one patient (3.6%) showed a small amount of pleural effusion. "A thickened pleural line was more frequently observed on US in patients with longer time intervals after the initial onset of symptoms," Zhang et al. noted, adding that pulmonary consolidations -- visualized as tissuelike hypoechoic regions, reflecting highly reduced air flow and increased quantity of inflammatory cellular exudate -- were more common in severe and critical cases.
Acknowledging that portable radiography could be just as useful in evaluating consolidation, "a bedside portable, handheld US system or even a robot-assisted tele-US system (a unique technique for physicians to remotely scan patients) further minimizes the number of health care workers and medical devices exposed to COVID-19," wrote Zhang and team.
The authors of this AJR article also proposed that severity scoring for lung US, similar to CT severity scores, should be developed to facilitate more accurate comparisons in future studies. make a difference: sponsored opportunity Story Source: Materials provided by American Roentgen Ray Society. Note: Content may be edited for style and length. Journal Reference:
Yao Zhang, Heng Xue, Mixue Wang, Nan He, Zhibin Lv, Ligang Cui. Lung Ultrasound Findings in Patients With Coronavirus Disease (COVID-19). American Journal of Roentgenology, 2020; 1 DOI: 10.2214/AJR.20.23513
Cite This Page:
American Roentgen Ray Society. "Lung ultrasound shows duration, severity of coronavirus disease (COVID-19)." ScienceDaily. ScienceDaily, 23 July 2020. <www.sciencedaily.com/releases/2020/07/200723115853.htm>.
Preventing the next pandemic
How $30 billion can prevent the next COVID-19
Date:July 23, 2020
Summary:A new article shows that an annual investment of $30 billion should be enough to offset the costs of preventing another global pandemic such as COVID-19.Share:
FULL STORY Thus far, COVID-19 has cost at least $2.6 trillion and may cost ten times this amount. It is the largest global pandemic in 100 years. Six months after emerging, it has killed over 600,000 people and is having a major impact on the global economy.
"How much would it cost to prevent this happening again? And what are the principal actions that need to be put in place to achieve this?" asked Andrew Dobson, a professor of ecology and evolutionary biology at Princeton. He and colleague Stuart Pimm of Duke University assembled a team to seek answers.
Their team has now written a Policy Forum article for the journal Science, a research-based opinion piece. In it, the multidisciplinary group of epidemiologists, wildlife disease biologists, conservation practitioners, ecologists and economists argue that an annual investment of $30 billion would pay for itself quickly.
"There have been at least four other viral pathogens that have emerged in the human population so far this century. Investment in prevention may well be the best insurance policy for human health and the global economy in the future," Pimm said. Two major factors loom large as drivers of emerging pathogens: destruction of tropical forests and the wildlife trade. Each has contributed two of the four emerging diseases that have appeared in the last 50 years: COVID, Ebola, SARS, HIV.
Both deforestation and the wildlife trade also cause widespread damage to the environment on multiple fronts, so there are diverse benefits associated with reducing them, note the researchers. Increased monitoring and policing of these activities would allow future emerging viruses to be detected at a much earlier stage, when control could prevent further spread.
All the credible genetic evidence points to COVID-19 emerging from a bat species traded as food in China. The wildlife trade is a major component of the global economy, with principal economic products including food, medicine, pets, clothing and furniture. Some of these are traded as luxury goods, which can create an intimate association that enhances the risk of pathogen transmission to the merchant or the buyer. Wildlife markets are invariably poorly regulated and unsanitary.
The organization tasked with monitoring international wildlife trade -- the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) -- has a net global budget of "a mere $6 million," said Dobson. "Many of the 183 signatories are several years in arrears in their payments."
The monitoring of this trade needs to be expanded, the authors argue. In particular, scientists need vital information about the viral pathogens circulating in potential food and pet species. They suggest using regional and national wildlife trade monitoring groups, integrated with international organizations for monitoring animal health. Monitoring and regulating this trade will not only ensure stronger protection for the many species threatened by the trade, it will also create a widely accessible library of genetic samples that can be used to identify novel pathogens when they emerge, say the authors. It will also generate a genetic library of viruses with two key roles: more speedily identifying the source and location of future emerging pathogens, and developing the tests needed to monitor future outbreaks.
Ultimately, this library will contain the information needed to speed the development of future vaccines.
Although there have been calls to close the "wet markets" where wild and domestic animals are sold, to prevent future outbreaks of emerging pathogens, the authors acknowledge that many people are dependent on wild-sourced foods and medicines, and suggest that better health oversight of domestic markets is required.
They suggest that the risk of new viruses emerging can be mitigated if more people are trained in monitoring, early detection and control of pathogens in wildlife trade, and working with local communities to minimize risks of exposure and onward transmission. "In China, for example, there are too few wildlife veterinarians, and the majority work in zoos and animal clinics," said co-author Binbin Li, an assistant professor of environmental science at Duke Kunshan University in Jiangsu, China.
"Veterinarians are on the front line of defense against emerging pathogens, and globally we desperately need more people trained with these skills," noted Dobson. The expansion and development of better ways to monitor and regulate the wildlife trade could be done for around $500 million a year, which the authors call "a trivial cost" when compared with the current costs of COVID, especially considering the add-on benefits such as curbing wildlife consumption and sustaining biodiversity. Slowing tropical deforestation would also slow viral emergence, plus it would reduce carbon inputs into the atmosphere from forest fires and protect forest biodiversity. On the other hand, it reduces revenues from timber, grazing and agriculture.
Is it worth foregoing these tangible, but economically focused, benefits? The authors undertake this part of their cost-benefit analysis from two complementary economic perspectives: first ignoring and then including the benefits of carbon stored as a hedge against climate change. They make no attempt to put a value on the loss of biodiversity. The Policy Forum article sharply focuses on the bottom-line costs needed to prevent the next COVID.
"Pathogen emergence is essentially as regular an event as national elections: once every 4 to 5 years," said co-author Peter Daszak, an epidemiologist with Ecohealth Alliance in New York, pointing to numerous studies. "New pathogens have appeared at roughly the same rate as new presidents, congressmen, senators and prime ministers!"
"We may see the costs of COVID soar to beyond $8 to $15 trillion with many millions of people unemployed and living under lockdown," said co-author Amy Ando, a professor of agricultural and consumer economics at the University of Illinois-Urbana Champaign. The annual cost of preventing future outbreaks is roughly comparable to 1 to 2% of annual military spending by the world's 10 wealthiest countries. "If we view the continuing battle with emerging pathogens such as COVID-19 as a war we all have to win, then the investment in prevention seems like exceptional value," Dobson said. make a difference: sponsored opportunity Story Source: Materials provided by Princeton University. Note: Content may be edited for style and length. Journal Reference:
Andrew P. Dobson, Stuart L. Pimm, Lee Hannah, Les Kaufman, Jorge A. Ahumada, Amy W. Ando, Aaron Bernstein, Jonah Busch, Peter Daszak, Jens Engelmann, Margaret F. Kinnaird, Binbin V. Li, Ted Loch-Temzelides, Thomas Lovejoy, Katarzyna Nowak, Patrick R. Roehrdanz, Mariana M. Vale. Ecology and economics for pandemic prevention. Science, 2020; 369 (6502): 379-381 DOI: 10.1126/science.abc3189
Princeton University. "Preventing the next pandemic: How $30 billion can prevent the next COVID-19." ScienceDaily. ScienceDaily, 23 July 2020. <www.sciencedaily.com/releases/2020/07/200723172208.htm>.
Driving immunometabolism to control lung infection
Date:July 23, 2020
Source:Trinity College Dublin
Summary:When drugs to kill microbes are ineffective, host-directed therapy uses the body's own immune system to deal with the infection. This approach is being tested in patients with COVID-19, and now a team of researchers has published a study showing how it might also work in the fight against tuberculosis (TB).Share:
FULL STORY When drugs to kill microbes are ineffective, host-directed therapy uses the body's own immune system to deal with the infection. This approach is being tested in patients with COVID-19, and now a team of researchers at Trinity College Dublin has published a study showing how it might also work in the fight against tuberculosis (TB). The findings are published in the journal Frontiers in Immunology today (July 23, 2020).
Although the bacteria that causes TB (called Mtb) has scourged humankind for millennia, we do not fully understand the complexities and interplay of the human immune response to this ancient bug. Worryingly, there are increasing numbers of people with antibiotic resistant TB, which is hard to treat and is becoming a global threat to public health.
Scientists at the Trinity Translational Medicine Institute (TTMI) at St. James's Hospital are dedicated to understanding the intricacies of the human immune response to Mtb with the aim of finding ways to target and promote the immune response to overcome the infection. Scientists already know that the human immune response can both under or over respond to the bacteria resulting in a difficulty to treat the disease. This complex immune response is analogous to driving with both the accelerator and the brakes fully engaged at the same time.
The research team led by Health Research Board Emerging Investigator, Dr Sharee Basdeo, and Professor Joseph Keane, Clinical Medicine, Trinity College has recently discovered a way to manipulate human immune responses to Mtb to tip the balance in favour of the patient. All changes in immune cell responses to an infection are governed by changes in what genes are active and 'open' for business. Because our DNA stretches out to nearly 2 meters but needs to fit inside every tiny cell in our body, it needs to be very tightly packed up. Its packaging, and how easy it is to open and close, very often dictates the activity of the genes. This is known as "epigenetics."
The research team used a drug approved for cancer treatment called suberoylanilide hydroxamic acid (SAHA for short, also known as Vorinostat). This drug is an epigenetic inhibitor, meaning it can block the machinery that closes up genes. Using this drug on human immune cells that are infected with the bacteria that causes TB, they discovered that SAHA releases the brakes on the immune system by stopping the production of an anti-inflammatory signal while at the same time promoting more appropriate pro-inflammatory signals that may help the patient to clear the infection. Importantly, the team discovered that this fine-tuning of the immune response early in the reaction to infection also benefits later immune responses, which may also aid in the design of future vaccine strategies.
Dr Donal Cox, Research Fellow, Clinical Medicine, Trinity College and senior author on the paper, suggests that this may be a new and exciting addition to our arsenal of antibiotic therapies. He said:
"Understanding and being able to manipulate the immune system is a crucial component of treating infectious diseases. Having host directed therapies targeting the human immune response will be key in addressing the likely pandemics that will arise in the future due to increasing antibiotic resistance, particularly TB." "We would also like to thank and highlight the important contributions that patients made in this study by providing blood and lung cells without which this research would not be possible."
This work was funded by grants from the Irish Research Council, The Royal City of Dublin Hospital Trust and the Health Research Board. make a difference: sponsored opportunity Story Source: Materials provided by Trinity College Dublin. Note: Content may be edited for style and length. Journal Reference:
Donal J. Cox, Amy M. Coleman, Karl M. Gogan, James J. Phelan, Cilian Ó Maoldomhnaigh, Pádraic J. Dunne, Sharee A. Basdeo, Joseph Keane. Inhibiting Histone Deacetylases in Human Macrophages Promotes Glycolysis, IL-1β, and T Helper Cell Responses to Mycobacterium tuberculosis. Frontiers in Immunology, July 23, 2020; DOI: 10.3389/fimmu.2020.01609