dexamethasone, a cheap, widely available steroid. A large clinical trial run by the University of Oxford showed that the drug cut the risk of death for COVID-19 patients on ventilators by a third, and by a fifth for those on oxygen.” data-reactid=”12″ type=”text”>Since the start of the COVID-19 pandemic, researchers have been working around the clock to find an effective treatment. The first drug to show promise is dexamethasone, a cheap, widely available steroid. A large clinical trial run by the University of Oxford showed that the drug cut the risk of death for COVID-19 patients on ventilators by a third, and by a fifth for those on oxygen.
not a panacea. Its beneficial effects are confined to critically ill COVID-19 patients in need of respiratory support. It has less impact on those with milder forms of the disease.” data-reactid=”13″ type=”text”>Peter Horby, the chief investigator on the trial, described the results as a “major breakthrough”. However, dexamethasone is not a panacea. Its beneficial effects are confined to critically ill COVID-19 patients in need of respiratory support. It has less impact on those with milder forms of the disease.
excessive inflammation – a complication often far more damaging than the virus itself.” data-reactid=”14″ type=”text”>What is encouraging about dexamethasone is that it provides a proof of concept for future therapies. The drug works by blocking the overactive immune response triggered by SARS-CoV-2, the coronavirus that causes COVID-19. This can cause excessive inflammation – a complication often far more damaging than the virus itself.
anti-inflammatory drugs now under investigation as a potential treatment for COVID-19. A large proportion of these drugs – many of which have appeared in the past few years – are monoclonal antibody (mAb) drugs. These drugs contain antibodies – Y-shaped proteins produced by the immune system to combat foreign substances, such as bacteria and viruses. In the case of anti-inflammatory drugs, the antibodies are engineered to block overactive cytokines, small proteins that regulate the inflammatory response.” data-reactid=”15″ type=”text”>Dexamethasone is just one of several anti-inflammatory drugs now under investigation as a potential treatment for COVID-19. A large proportion of these drugs – many of which have appeared in the past few years – are monoclonal antibody (mAb) drugs. These drugs contain antibodies – Y-shaped proteins produced by the immune system to combat foreign substances, such as bacteria and viruses. In the case of anti-inflammatory drugs, the antibodies are engineered to block overactive cytokines, small proteins that regulate the inflammatory response.
Antibodies have been used to fight disease ever since the closing decade of the 19th century when it was found that serum from animals that had survived diphtheria and tetanus conferred immunity in animals with no previous exposure to such diseases, and could cure the diseases. This form of treatment, known as serum therapy, was so successful that it was the mainstay of treatment for infectious diseases until the rise of antibiotics.
For much of the 20th century, the only source of antibodies were those that could be obtained from serum extracted from the blood of previously immunised animals. This, however, was a time-consuming and expensive process, impossible to standardise.
after a breakthrough made at the Laboratory of Molecular Biology, Cambridge, England, by César Milstein, an Argentinian immunologist, and Georges Köhler, a German biologist. In 1975 they published a technique to produce limitless quantities of identical antibodies to a specific target.” data-reactid=”29″ type=”text”>The situation only changed after a breakthrough made at the Laboratory of Molecular Biology, Cambridge, England, by César Milstein, an Argentinian immunologist, and Georges Köhler, a German biologist. In 1975 they published a technique to produce limitless quantities of identical antibodies to a specific target.
The method involves creating a hybrid cell line, known as a hybridoma, by fusing a short-lived antibody-producing B cell, a type of white blood cell, collected from the spleen of an immunised animal with an immortal cancer cell line. Maintained in a medium, the hybridoma can generate large quantities of what is known as “monoclonal antibodies”. The term “monoclonal” denotes the fact that the antibodies are all identical and clones of a unique parent cell.
treat people. The first mAb drug was licensed in 1986. Since then, more than 80 mAb drugs have been licensed in the US and Europe. They now make up a third of all new medicines introduced worldwide. Most of these are directed towards cancer and autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis.” data-reactid=”31″ type=”text”>Awarded the Nobel prize in 1984, Milstein and Köhler’s invention was soon used to treat people. The first mAb drug was licensed in 1986. Since then, more than 80 mAb drugs have been licensed in the US and Europe. They now make up a third of all new medicines introduced worldwide. Most of these are directed towards cancer and autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis.
Despite their success, little attention has been paid to the potential of mAb drugs for treating COVID-19. This is somewhat surprising given their strong track record for treating immune disorders. Also, they are much quicker to develop than the vaccines and antiviral drugs currently grabbing the limelight.
shift towards developing mAb drugs to treat infectious diseases.” data-reactid=”37″ type=”text”>Part of the explanation may lie in the fact that only three mAb drugs have so far been licensed for infectious diseases. The slow progress in this area stems from the dominance of antibiotics, which are cheap to make and easy to take. However, because of the rise of antibiotic resistance, attitudes have recently begun to shift towards developing mAb drugs to treat infectious diseases.
In the past, mAb drugs were considered unsuitable for infectious diseases because they are very expensive to make. But advances in recent years have helped to reduce their cost.
Another obstacle is the fact that mAb drugs need to be given intravenously. But this is not such an issue for seriously ill COVID-19 patients who already receive intravenous infusions in intensive care.
other conditions are now being tested for COVID-19. They include drugs used to treat rheumatoid arthritis and other inflammatory conditions. Among them is infliximab, which made history in the 1990s by overturning the conventional view that a mAb drug would never succeed as a treatment for inflammatory disorders.” data-reactid=”40″ type=”text”>Several mAb drugs already approved for other conditions are now being tested for COVID-19. They include drugs used to treat rheumatoid arthritis and other inflammatory conditions. Among them is infliximab, which made history in the 1990s by overturning the conventional view that a mAb drug would never succeed as a treatment for inflammatory disorders.
Passive immunisation
passive immunisation, this type of preventative treatment has been used for centuries.” data-reactid=”42″ type=”text”>Aside from their potential to curb COVID-19 related inflammation, mAbs could help in another way. They could be used to protect people at high risk of exposure to the infection, such as healthcare workers, and people with compromised immune systems, such as those receiving chemotherapy. Known as passive immunisation, this type of preventative treatment has been used for centuries.
The mAbs used for passive immunisation are very different from those used for treating the inflammatory components of COVID-19. It involves using mAbs specifically targeted against the SARS-CoV-2 virus. Such mAbs have a couple of advantages over vaccines: they are much faster to develop and they provide immunity within minutes. The downside is that the protection only lasts for a short time – typically months.
Several teams around the world are now creating mAbs against SARS-CoV-2 for passive immunisation. The first ones are expected to enter clinical trials next month. If successful, they will be helpful in the absence of a vaccine.” data-reactid=”44″ type=”text”>Monoclonal antibody drugs proved successful for passive immunisation during the Ebola virus outbreak in West Africa between 2013 and 2016. Several teams around the world are now creating mAbs against SARS-CoV-2 for passive immunisation. The first ones are expected to enter clinical trials next month. If successful, they will be helpful in the absence of a vaccine.
The Conversation under a Creative Commons license. Read the original article.” data-reactid=”45″ type=”text”>This article is republished from The Conversation under a Creative Commons license. Read the original article.
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]]>As a physician in New York City, it’s become my work — both in the hospital and with my family and friends — to field questions about coronavirus. Today’s hot topic is antibody testing, and I’ve been asked daily where people can get this new diagnostic breakthrough. My answer, however, is as disappointing as it is urgent: Avoid current antibody testing altogether. Our scattered, and unscientific approach to antibody detection is worse than useless, and individual testing threatens to cause real harm.
During this pandemic, rapidly changing and seemingly conflicting recommendations have left us in a state of scientific whiplash. With so many doctors, hospitals, and private labs hastily promoting individual testing, we must take a step back and decide if this is truly the best course of action. Each breakthrough in diagnosing and treating coronavirus brings us to a crossroads, an inflection point where we have the opportunity to either hastily proceed as individuals or thoughtfully create a collective approach. Now that FDA-approved tests are finally at our doorstep, it’s time to hit the brakes. The truth is that individual testing brings us nowhere, and rushing into a disorganized, private testing free-for-all will only set us back in the fight against this devastating pandemic.
Even something as simple as “accuracy” depends on our ability to carefully conduct testing and analyze the results. The best tests on the market — which now boast “over 99 percent accuracy” — use laboratory calculations called “specificity” and “sensitivity” to back up these claims. But these numbers are just the beginning in calculating what false negative and false positive rates look like in the real world. False negatives are more likely in an area where a disease is very common, due to simple probability.
Conversely, it’s much harder to trust a positive test result in an area where the disease you are looking for is quite rare. And there are more probabilities that come into play. A negative result is more likely to be false than real if our suspicion for a disease is already very high, while we should be wary of any positive test result in a patient whose presentation makes disease diagnosis exceedingly unlikely. Even a pregnancy test that boasts “99.9 percent accuracy” will be positive for 1 in 1000 biological males who take it. Without a careful and critical eye, even the most “accurate” test results are meaningless.
Many — doctors included — feel that a potentially incorrect test result is better than nothing. But isolated results are not only unreliable, but they are also impossible to interpret clinically. We don’t yet know which antibody levels are protective, or how long this protection lasts. We also know from other viruses that even people without detectable antibodies can have some disease protection if they were exposed to the disease. For now, even “correct” antibody tests don’t translate into immunity. For many, negative results will do nothing more than cause unneeded anxiety increases. And for others, positive results of unclear significance will give a false sense of security, amplifying cabin-fever, and detracting from systematic, regulated, and sensible return-to-work and reopening of society.
Most important, random testing without a clear strategy detracts from the organized testing efforts that we need to move forward. We’ve seen how important coherent testing strategies are in other countries. In Germany and South Korea, organized testing that informed contact tracing, isolation, and high-level policy was a crucial part of a response that led to early coronavirus containment and enviably low fatality rates. Widespread testing and speed of action are key to successful public health policy. But this only matters if data can be collected, organized, and translated into cogent, scientific policy. With antibody testing, which is far more challenging to interpret than nasal PCR results, critical interpretation of a large dataset is the key to making this information meaningful.
The lessons of the pandemic are hard-learned and filled with endless loss. “Accurate” antibody testing presents us all with a chance to learn from our mistakes. Let us pause and ask our leaders to sit with scientists, and to create a smart and thoughtful plan of action jointly. It is as important to act strategically as it is to react quickly. For now, we must all say “no” to individual antibody testing and demand a clear testing plan so that this breakthrough translates into real progress. It will take longer to see our own antibody levels, but the results we get will have meaning.
Rebekah Diamond M.D. is an assistant professor at Columbia University Medical Center and a hospital pediatrician at NewYork-Presbyterian. The views expressed here are entirely her own and do not necessarily reflect those of her affiliated institutions.
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