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kwilson5 · 5 years ago

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A tiny organism, only the size of nanometers, has disrupted the flow of ordinary life. This organism is a virus, called SARS-CoV-2, and it is the driving force behind the COVID-19 outbreak. Though undetectable to the naked eye, researchers around the world are stressing the importance of identifying hosts of the lethal virus. Widespread testing could help identify and isolate patients, helping to flatten the curve of COVID-19 infection. Currently, there is only one method of testing, and it is relatively costly and time consuming. This lack of efficient testing leaves humanity at a serious disadvantage in the arms race against SARS-CoV-2. In an attempt to remediate this issue, this study has suggested using serological testing to help meet testing needs. The study found that serological testing is an effective testing method for SARS-CoV-2 with its fast turn-around, low workload, and ability to predict the severity of symptoms.

As of April 9th, 2020, there were over 1.5 million confirmed cases of COVID-19 worldwide. These cases were confirmed through RNA testing, the only testing method currently available. RNA is the genetic material of viruses, which can be detected in samples of the upper respiratory tract, collected via swabs of the throat or nasopharyngeal tract. The samples are then analysed for the unique genetic markers of SARS-CoV-2. While RNA testing has high accuracy, it has low real-life performance. For one, sample collection and analysis is very sensitive to contamination, and measures to ensure sterility are timely and expensive. As such, testing is often restricted to health care workers, individuals with direct contacts with confirmed patients, and patients with symptoms characteristic of COVID-19. Additionally, RNA testing sensitivity is highest at the beginning of the illness so viral RNA may not be detectable during later stages of infection. As a result, RNA-based testing is not a practical option for widespread testing, creating a bottleneck for early detection and monitoring of COVID-19 patients.

In pursuit of a serological test for SARS-CoV-2, a research team led by Juanjuan Zhao studied the antibody response in COVID-19 patients. Their hope was to find a consistent antibody response that can be readily and reliably identified using serological testing. Serological testing is an indirect form of testing that detects the immune response in the form of antibodies, instead of the presence of the virus itself. Antibodies initiate a targeted defence against intruders and bind to the proteins on the surface of the virus with lock-and-key precision. These antibodies are formed early after the onset of infection and can be detected in body fluids. To perform a serological test, a blood sample is collected and analysed for the antibodies specific to the virus of interest. The presence of antibodies is assessed using an enzyme-linked immunosorbent assay, also known as ELISA. ELISA uses an antigen that mimics the spike protein found on the surface of the SARS-CoV-2 virus. As such, antibodies can bind to the antigen used in ELISA the same way that they would bind to the virus. Then, an enzyme binds to the antibody-antigen complex and produces a colored reaction so that the presence of antibodies can be detected. This process is illustrated in the figure below.

For Zhao’s study, blood samples were collected from 173 COVID-19 patients to test for Ab, IgM, and IgG antibodies. Ab is to the overall antibody response, while IgM and IgG are specific immunoglobulin antibodies that circulate in the blood. A total of 535 blood samples were collected from patients at different stages of infection and assessed for antibodies using the ELISA method described above. The Ab assay was found to be the most sensitive test and produced a positive result sooner after onset than the assays for IgM and IgG. In 90% of patients, the Ab assay produced a positive result by the 12th day after onset of illness, and 100% of patients had a positive result one month after onset. As a result, serological testing for Ab is effective for detecting SARS-CoV-2 during later stages of illness.

Serological testing is much more efficient than RNA testing as it has a faster turn-around time and high throughput, meaning it has the potential for widespread testing. Widespread testing will help flatten the COVID-19 curve by enforcing quarantine of confirmed patients and allowing for contact tracing of other potential carriers. Unfortunately, access to testing is currently restricted all around the world. Priority for testing is given to health care workers, individuals with close contacts to a positive case, and people with characteristic symptoms of COVID-19. However, it is believed that there could be a large number of asymptomatic carriers at large in our society, contributing greatly to viral spread. Because serological testing is a relatively quick and cheap method of screening for infection, it could be used to identify these carriers and impose quarantine.

Serological testing also has the potential for uses beyond diagnostics. For one, the concentration of Ab in a patient’s blood sample can be used to predict the severity of illness. Zhao and colleagues found that patients who developed a critical condition had experienced a marked increase in Ab concentration approximately 2 weeks after onset. Additionally, serological testing has been suggested as a way to screen employees before they return to work. It is possible that the presence of antibodies in individuals who are no longer ill may be linked to some immunity against the virus. First, further studies are required to better understand the immune response to SARS-CoV-2. If proven to be true, serological testing could a useful tool to revive the economy.

Serological testing, as proposed by Zhao and colleagues, has the potential to significantly increase the number of COVID-19 diagnostic tests administered worldwide. Serological testing is much cheaper, more timely and easier to administer than RNA testing. As such, it is a more practical option for widespread testing of non-priority individuals. Serological testing could also be used in addition to an RNA test to increase confidence of diagnosis or identify false negatives. Furthermore, serological testing could be used to identify high-risk COVID-19 patients, or as a screening mechanism to revitalise the depleted workforce.

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kwilson5 · 5 years ago

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An Old Solution to a New Problem?

Within the first month of 2020, the world as we once knew it descended into chaos. Governments all over the globe rung their alarm bells as COVID-19 spread from Wuhan, China, to all four corners of the Earth. World leaders and medical experts alike were left dumbfounded at the unprecedented turmoil caused by the new disease.

As COVID-19 runs rampant on humanity, a “cure” is everyone’s first priority. Presently, the only defence against infection is social distancing. Meanwhile, pharmaceutical companies worldwide rush to create a vaccine. However, even the most optimistic predictions anticipate that the novel vaccine is at least a year away. As citizens wait idly by, while thousands die each day, the distant timeline leaves the world feeling helpless.

While the race to a new vaccine unfolds, scientists scramble to find more timely treatments. An unorthodox solution has been proposed: a century-old vaccine. The bacillus Calmette-Guerin (BCG) vaccine is routinely used to prevent tuberculosis. The vaccine is inexpensive, accessible, and has very few side effects. Recently, it has attracted attention for its indirect benefits. Research has found that BCG initiates a general immune-boosting effect. By enhancing white blood cells, BCG strengthens the immune system’s defences against unfamiliar viruses. White blood cells inhibit viral replication, limiting symptoms and decreasing spread of infection. The BCG vaccine has been proposed for SARS-CoV-2, the virus responsible COVID-19.

Trials testing the beneficial effects of BCG against COVID-19 are underway. Thousands of healthcare workers in Australia, the Netherlands and the United States are undergoing a six-month trial to put the vaccine to the test. If effective, BCG would be the first vaccine repurposed in this way. The possibility of using an old vaccine to combat a new virus is both exciting and hopeful, as it could be available much sooner than a new vaccine.

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kwilson5 · 5 years ago

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kwilson5 · 5 years ago

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Picture this: a red, itchy rash; oozing blisters; full body aches and pains. Does this ring a bell? For many, these symptoms bring back memories of the chickenpox, an illness once seen as a childhood rite of passage. Thankfully, these memories are becoming a thing of the past. The widespread use of the chickenpox vaccine has significantly decreased the rates of infection, as well as the associated burden on health care. The publicly funded vaccine program in Canada prevents over 3.5 million cases of the chickenpox, and approximately 9,000 hospitalizations each year. Decrease in infection rates are thanks to the efficacy of the vaccination: the recommended two-doses of the vaccine is 98% effective at preventing illness for at least 10 years after vaccination, and prevents 100% of severe infections. Medical experts and parents alike would agree that the chickenpox vaccine has been successful method of controlling chickenpox infection.

Of course, everything has its critics, and the chickenpox vaccine is not immune to public scrutiny. Parents are, and should be, critical with everything related to their child’s health. As such, the topics of vaccines and vaccine safety continue to attract attention in the media, both good and bad. Much of the negative attention is attributed to misformation that has found its way into public eye, often being shared by “anti-vaxxer” groups. Some forms of vaccine criticism are more valid than others, while some are outright crazy. Throughout this blog post, I would like to discuss a specific myth associated with the varicella vaccine, which links the widespread use of the chickenpox vaccine with increasing rates of adult shingles.

So, what is the myth, and where does it come from? There is an increase in shingles cases, and people think the chickenpox vaccine is to blame. This idea is based by a hypothesis first introduced by Hope-Simpson in 1975, and is known as the Exogenous Boosting Hypothesis. It is the idea that routine vaccination against the chickenpox removes a natural “booster” from the community, which supposedly protects unvaccinated age groups against reactivation of the chickenpox. This idea has become increasingly popular as cases of the shingles continue to rise. Over the past 60 years, cases have increased by 24% in all age groups. News reporters, anti-vaxxers, and other bloggers have cited the Hope-Simpson Exogenous Boosting Hypothesis as evidence that the chickenpox vaccine is the cause of this increase. Mathematical models have used this hypothesis to predict an impending increase in shingles cases, and The British National Health Services have avoided added the chickenpox vaccine to their routine vaccination schedule for this reason. The popularity of this opinion leads one to wonder… is there any truth to it?

To begin unraveling the alleged link between varicella vaccinations and shingles infections, it is important to first understand the mechanisms of infection. Both chickenpox and singles are caused by the same virus: varicella. Primary infection with varicella often occurs in childhood, causing chickenpox. Chickenpox causes flu-like symptoms accompanied by a tell-tale rash. Most children recuperate in just over a week, but a severe infection may lead to pneumonia or inflammation of the brain. Thankfully, once recovered, reinfection is rare. This is because of natural immunity. Natural immunity arises when infection occurs and triggers a cell-mediated attack on the virus by the immune system. The immune system will then be able to remember the virus the next time it is encountered, and will be able to initiate another specific, cell-mediated response to prevent reinfection. Chickenpox is common in children because they have not yet acquired natural immunity against varicella; but once they contract it, reinfection is rare.

Sadly, natural immunity to the chickenpox comes with a cost. Infection with chickenpox causes latency, putting an individual at risk for secondary infection with shingles. During primary infection, the immune system destroys cells infected by varicella. However, some cells hide in the ganglionic neurons of the nervous system, which cannot be reached by the immune system. These viral cells can lay dormant in the immune system for a lifetime, which is referred to as latency. During latency, varicella is not known to cause any neuronal damage, and it can remain forever inactive. However, 30% of individuals with latent varicella experience a secondary infection with shingles. Risk of secondary infection increases with age and in individuals who are immuno-compromised, through a process called immunosenescence. Immunosenescence is a decrease in the efficiency of cell-mediated responses, increasing vulnerability to viruses like varicella. In instances of immunosenescence, dormant varicella may become reactivated, causing a secondary infection known as shingles.

Figure 1: Latency and reactivation of varicella after primary infection with the chickenpox.

The Exogenous Booster Hypothesis suggests that circulating chickenpox can strengthen natural immunity against the chickenpox to protect unvaccinated age groups from secondary infection of varicella. Brief encounters with individuals who are ill with varicella should have a “boosting” effect on someone who has latent varicella. A small amount of the virus will inoculate the immune system to strengthen natural immunity, much in the same way that a vaccine works to provide immunity. However, there has not been any research to support this hypothesis since it was first introduced by Hope-Simpson. Multiple studies, including this meta analysis, have not found any evidence to support the Exogenous Booster Hypothesis. In other words, a decrease in exogenous boosting is unlikely to be the cause of increased shingles rates. While researchers still aren’t sure what is the cause, they have suggested a few likely culprits. Most likely, this is related to immunosenescence in an ageing population. Additionally, an increased use of therapies that influence immune functioning, such as chemotherapy, are believed to decrease natural immunity.

Regardless of the reason, one thing is sure: the number of shingles cases are increasing, and vulnerable populations should do what they can to prevent illness. Luckily, modern medicine has provided an alternative to using sick kids as a source of immunity. There are vaccines available to protect older adults from shingles and associated complications. The vaccine is the only reliable method of preventing shingles.

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kwilson5 · 5 years ago

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Misinformation: The Social Media Pandemic

Thanks to vaccines, people are not dying from preventable illnesses at the same rate as in the past. These shots prevent over 2 million deaths each year. But vaccines are not effective when they are not being administered. Recent waves of anti-vaxxers have had a scary influence on vaccination rates: a recent study has revealed that between 2012-2015, HPV vaccination rates decreased by nearly 50% for Denmark girls.

Human Papillomavirus, or HPV, is the most common STI. The HPV vaccine is safe, effective, and prevents an estimated 90% of cervical cancers. In Denmark, the vaccine is free for teenage girls. So why aren't girls being vaccinated?

One word: misinformation. In 2012, 95% of girls were vaccinated against HPV. In 2013, vaccination rates dropped to 83% after newspapers accused the HPV vaccine of serious side effects. Then, in 2015, TV2 Denmark aired a sensationalized documentary called “The Vaccinated Girls - Sick and Abandoned”, which sunk rates to 51%. In just 3 years, anti-vax propaganda caused a 50% drop in HPV vaccination rates.

Thankfully, health authorities were able to step up and squash the misinformation. In May 2017, an information campaign took over Danish communities and digital platforms with the goal of decreasing cervical cancer. The campaign included town hall meetings, social media ads, and the Twitter hashtag #stopHPV. The result? A 109% increase from the vaccination rate in 2015.

So, what can we learn from this? Social media is an incredibly powerful tool, and it must be used for good. When misinformation is available, it can have a drastic influence on society. Vaccination rates in Denmark are a prime example of the consequences of misinformation. On the other hand, the internet can be profoundly useful for communicating and informing medical knowledge. As individuals, it is our responsibility to be critical about everything we see and share to prevent the spread of lies online.