May 2020 - SciWriteGlobal

May, 2020

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

The human body is well known to host a large number of microbes, mostly harmless but when triggered might turn virulent. A large fungal ecosystem resides inside a human body mainly including Candida species, constituting a large part of the human body’s microbial flora. Usually asymptomatic, Candida forms small colonies, but when triggered such as environmental change, can potentially help the microbes to break barriers and cause life-threatening diseases.

Though multiple numbers of antifungal drugs are available, it is recently found that Candida species is capable of building resistance against the drugs by forming biofilms. The article further talks about the environment within the host body paving way to such resistance.

Within the human host, Candida is capable of changing morphology and functions according to the change in the environment it resides in. Several factors play a role including temperature, ph, and oxygen supply. Candida depending on the environment can take forms such as hyphae, budding, or even pseudohyphae.

Another crucial role played in a microbial existence within the human host is nutrients availability. It is reported that microbes thrive in the area of high glucose content. When deprived of glucose is when microbes turn to another source of nonfermentable nutrients. Research performed in labs using Candida flora has reported that in the presence of glucose the microbe is known to morph into hyphae and promote antifungal resistance.

The limitations of micronutrients such as iron magnesium, and copper are known to limit the growth of invading microbes. But this is quite tricky as micronutrients are needed both by the host and microbes in functioning such as biochemical and cellular functions.

It is very well known that oxygen and ph levels vary within every niche in the human body. While some are alkaline and high on oxygen concentration others are hypoxic and acidic. Candida microbes being versatile they are, can adapt their cell walls according to the change in ph. It is also interesting to note that Candida microbes thrive under hypoxic conditions, inducing their hyphal growth and causing immune evasion.

The above has described the flexibility of the microbes to overcome multiple constraints faced in the host body. This ability of Candida helps it to form colonies and invade niches around the body. Another strategy imparted by the microbes is biofilm formation against the host body or biomedical devices. Biofilms consist of a 3D community of adherent cells with different biological properties. These cells are embedded in the ECM, which helps in maintaining the overall integrity of the biofilm. The ECM also acts as a protective barrier against any drug invasion. These features play a crucial role in Candida microbes resistance against antifungals and biomedical devices.

With the emergence of resistant Candida species, the need to develop new antifungals is inevitable. Research using an in vivo model to mimic the host conditions is giving close insights to unravel the mysteries of the microbes. These approaches are paving the way to novel therapeutic vaccines and anti-fungal treatments, enhancing the body’s ability to fight off the infections.

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May, 2020

Artificial intelligence-enabled rapid diagnosis of patients with COVID-19

Since December 2019, multiple cases of pneumonia due to unknown reasons have emerged in Wuhan, China. Through testing multiple patient samples, scientists extrapolated a new coronavirus termed COVID-19. With no FDA approved therapeutics or treatment available for the disease, diagnosis plays an important role in containing COCVID-19, giving a path to the rapid implementation of control measures to limit the spread. With the disease spreading to almost 100 countries, a million cases have been confirmed worldwide to date. Imaging is one of the main principles used in diagnosing and evaluating the disease, with the final diagnosis depending on reverse transcriptase-polymerase chain reaction (RT-PCR).

In response to the growing number of COVID-19 cases, there is currently a shortage of diagnostic kits worldwide. Multiple industries are coming forward to develop rapid, easy to use diagnostic kits to facilitate testing. However before these kits can be commercialized, they must be tested and validated. With the current available tests taking almost 2 days to complete and produce a result, serial testing is required to rule out any negative cases. Additionally, it is a mystery as to whether an RT-PCR is a gold standard and whether a false positive/ negative result is common. The above reasons highlight the need for alternative testing methods to produce rapid and accurate results to identify, isolate, and treat the affected people.

Chest computed tomography is also a much-used valuable component in testing COVID-19. With some of the patients showing early-stage symptoms in radiological finding, limits the CT ability to differentiate between a positive and negative case. In this current study, the authors have used Artificial Intelligence (AI) algorithms to help in integrating CT scanning in finding the symptoms of the virus, exposure history and reliable lab testing to rapidly diagnose the patients affected with COVID-19.

A trial was performed on 905 patients diagnosed using RT-PCR and next-generation RT-PCR and around 46% (419) people were declared positive for COVID-19. Parallelly in a test set of 279 participants, the AI system managed to achieve accuracy to about 92% of the population and had equal or even better sensitivity than a senior radiologist. The AI system also improved the detection of COVID-19 positive patients with negative CT scans, identifying 17 out of 25 participants who were tested positive via RT-PCR but negative with normal CT scans. In comparison, the radiologists’ declared the said 17 participants to be COVID negative.

AI shows signs of analyzing huge amounts of data quickly, a quality that is much needed in the current pandemic. A major limitation of the above study is the small sample size, with available CT scans and clinical history data, the AI system can help in diagnosing COVID-19 patients rapidly. Though a promising tool, further data collection is required to test the generalization of AI mapping on other patient populations.

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May, 2020

A brief insight on ACE receptors role in COVID-19

With the novel coronavirus, COVID-19 is spreading across the world and the fact that no drug or treatment has been found against it is creating fear among people. Coronavirus is a large family of enveloped, single-stranded RNA that infects mainly mammals including humans. In humans, coronavirus causes mild to severe respiratory illness. These viruses exhibit strong virulence and are highly contagious. While a person infected, produces mild symptoms, certain individuals respond severely, sometimes leading to death.

The SARS pandemic, back in 2002 is known to belong to the same family of viruses as COVID-19. According to WHO, SARS rapidly spread through 29 countries, with 8096 confirmed cases, but the current pandemic has surpassed all numbers by infecting over millions of people across the world. Today, it is due to SARS that has resulted in a coordinated effort to develop treatments targeting the virus or host cell components responsible for viral replication.

The deadly virus, COVID-19 enters the human body and binds to the target cells through angiotensin-converting enzyme 2 (ACE2) which is mainly expressed in endothelial cells and Leydig cells. ACE-2, a transmembrane metallo carboxypeptidase, is an enzyme which for years has been important for the treatment of hypertension. With further Polymerase Chain Reaction (PCR) analysis it was determined that the ACE-2 receptor is also present in the lung and gastrointestinal tract, tissues harboring COVID-19.

Inhibiting ACE2 receptor blocks COVID-19 entry:

ACE-2 belonging to the family of ACE receptors, plays a key role in the Renin-Angiotensin System (RAS) and in the treatment of hypertension. ACE2 is known to degrade angiotensin II and thereby, negatively regulating RAS. Recently experts have revealed that the COVID-19 virus uses ACE-2 receptors as their entry in HeLa cells. Additionally, it was found that by using anti- ACE-2 antibodies in other mammals like monkeys, it was seen that there was an entry blockage of pseudotypes expressing the COVID-19 virus.

For the virus to enter the host cell, its spike glycoprotein (S) needs to be cleaved at 2 sites, termed S protein primming so the viral and host cells membrane can fuse. A serine protease TMPRSS2 is essential for cleaving the S protein. It was found by treating Calu-3 human lung cell line with a serine inhibitor- camostat mesylate the entry of the COVID-19 virus was partially blocked. Angiotensin-converting enzyme (ACE) inhibitors is also found to play a role in preventing the formation of angiotensin II. ACE multifaceted functions include treating heart failure, controlling high blood pressure, and preventing kidney failure in diabetic patients.

Existing concerns about ACE inhibitors:

Though ACE inhibitors might seem like a promising solution for COVID-19, there are certain concerns regarding the increased susceptibility to COVID-19. These are considered based on the fact that ACE inhibitors are also used in treating millions of people with hypertension, heart, and kidney disease. When administered with inhibitors, diabetes and hypertension patients were observed to have an increase in ACE2, which in turn would facilitate infection with COVID-19. It is hence hypothesized that treating diabetic and hypertension patients with ACE inhibitors might make them more susceptible to COVID-19.

Furthermore, several studies have reported that long term usage of ACE inhibitors can modify the adaptive immune response, which is a key and much-needed defense against any infection. These particular effects must be taken into noticed and investigated further in context to COVID-19.

Road to COVID-19 therapies:

These findings could greatly impact the efforts being taken in developing treatments for the current pandemic. For instance, TMPRSS2 inhibitors can be potentially used to prevent virus entry into the host cells. Though there are certain drawbacks in using ACE inhibitors, there is a lack of scientific evidence and clinical data to support the discontinuing of ACE inhibitors in COVID-19 patients with existing hypertension and diabetes. The proof that reduction in mortality due to ACE inhibitors and the beneficial effects outweigh the theoretical risks.

Our interpretation of this hypothesis should not lead to changing drugs for patients with diabetes or hypertension, without consulting an expert physician. Though it’s of utmost urgency for the scientific community to come up with some solution for this deadly virus, further research and clinical trials need to be performed before any of the said theory can become a reality.

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May, 2020

Mutant Poliovirus from vaccine more infectious than the wild type

How it all began?

Back in the 20th century, there were many more diseases that worried parents then Polio did. Polio struck during summer, making its way through towns, every few years. Most people were reported to recover quickly, though some suffered temporary or permanent damage leading to paralyzation and even worse, death. With many polio survivors disabled for life, it was a constant reminder to the society the toll it took on young lives. Polio reached the level of epidemic proportions back in the 1900s affecting the infant and young kids, where the infant’s immune system is still aided by maternal antibodies could not fight the virus.

Polio is caused by a family of viruses belonging to the Enterovirus genus. These viruses are highly contagious usually spreading through contact with people either by oral or nasal secretions, or by contacting a contaminated area. The virus enters the mouth and is found to multiply by the time it reaches the digestive tract, where it continues to multiply. In cases of paralytic polio, the virus makes its way from the digestive tract to the bloodstream attacking nerve cells.

Development of vaccines to eradicate polio:

A vaccine is made from a very small amount of wither weak or dead germs that cause the disease, for example-poliovirus. When administered, the vaccine introduces the said virus into the body to trigger an immune response, causing it to recognize and combat the actual disease if encountered in the future.

The antibodies specific to the poliovirus was first discovered in 1910. Using immunologic techniques, it was in 1931 different serotypes of the poliovirus were identified. By identifying that the virus can be grown in large amounts using tissue culture, it was just a short time before the first inactivated polio vaccine (IPV) was developed. With human trials being deemed a success, the number of polio cases drastically dropped over the years. Later an improved version of the vaccine using live attenuated virus was developed, which could be administered orally, known as oral poliovirus vaccine (OPV). Soon it became the predominant go-to vaccine for developing countries all over the world, declining the number of cases drastically till a new problem raised recently.

Vaccine-derived poliovirus:

Over the past few years, more than 10 billion doses of OPV have been administered to millions of children worldwide, preventing more than 10 million cases during that period, bringing down the number of cases drastically.

So far in the year 2017, only as many as 6 “wild” polio cases were detected worldwide. By wild it means that the number of cases affected by polio “wild type” strain found naturally in the environment. Recently, new cases have been reported of children paralyzed by a vaccine-derived poliovirus. Around nine new cases were identified in countries- Nigeria, the Democratic Republic of the Congo, Central African Republic, and Angola last November, along with Afghanistan and Pakistan. The WHO reported that as long as a single child is infected, all the other children are at risk.

In developing countries, the oral vaccine is used profusely among all children due to its low cost and accessibility. The vaccine-associated paralytic polio is caused by a strain of poliovirus which was previously termed wild type. The onset was found to be caused by a type 2 virus contained in the oral vaccine. Type 2 virus was a wild type virus eradicated years ago, but in rare cases can mutate into a form that can breach the vaccine protection.

Erradication possible:

With the COVID-19 outbreak, the WHO has also additionally undertaken the goal of eradicating the new mutant poliovirus before its too late. The role model here is smallpox, which was completely wiped out thanks to a consistent vaccination strategy. The same applies to polio. Similar to smallpox, the polio vaccine also offers impeccable protection, though not applicable to virus mutants. Reports state that the latest mutant outbreak is due to the low vaccination rates. The rise in vaccine-derived polio cases is due to the mutant form of the disease affecting the non-vaccinated children through contaminated matter.

The coverage of vaccination and hygiene measures must be extended so that the new mutant can no longer continue to survive, the same way the previous polio epidemic in Congo was eradicated. Though the current vaccines appear to be good enough to be effective, the new pathogen is nonetheless a warning. The need for new protectant vaccines is more important now than ever. It is only this way there is a chance of permanently wiping out polio.

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May, 2020

Difference between a blog and an article- Simplified

Ever wonder what is the difference between a blog and an article? It’s a topic that makes people wonder. Though they are often used interchangeably, an article and blog post are not the same thing. No matter what, it all starts at one point “great content”. Great content helps you stand apart from the crowd.

With digitization expanding at a fast pace, everyone is switching coherently towards it, where content reigns king! In the era of digitization, without content, you will not be able to convey your intentions to the audience. That’s where understanding the material required, plays a major role for researchers and scientists. Here’s an in detail look at the difference between a blog and an article.

Writing style and length:

A most noticeable difference- a blog is a relatively new form of writing, whereas an article has been existing for hundreds of years now. A blog is usually written from a personal perspective, an inside point of view. Based on this it is safe to say, a blog is something more casual and provides a great way for you to personally connect with the audience you are trying to reach.

It can include interviews and facts, however, it should be based on experience and should include more personality.

While on the other hand articles usually have a more sophisticated and journalistic tone due to the amount of detailed information involved. The author’s opinion is not encouraged and is mostly kept formal, where an editor is usually involved.

Blog posts are usually short in nature, consisting of around 500 words but this is not the limit. You can also find blog posts as long as 1000-1500 words. However, it is recommended to post short blogs to keep your audience engaged as people don’t prefer reading long items. The usage of the first-person language and recent updates makes it easy for the audience to relate to what you are trying to convey. Blogs are meant to be intriguing, capturing but don’t usually contain a lot of intellectual tones usually found in an article. It is meant to be more laid back and even amusing in some cases. On the other hand, an article is crafted by a third person point of view, and is usually long with a minimum of 1000 words. They use more intricate language that discusses the topic more formally.

The purpose:

The informal nature of a blog makes it relatively easy to write. They serve the purpose of instant satisfaction- an urge to communicate. If the goal of yours is to build a relationship with your target audience, a blog is your friend. It will help you convey a great amount of information without getting into the little details.

Articles cannot be scanned through with ease like a blog, due to the fact that it is not their sole purpose. A lot of time is invested by the author in carrying out long hours of research and creating content to convey detailed information to make sure it gives the targeted audience a feel of sitting in a classroom.

Editing:

A blog post is to keep your audience up to date. It is usually published on a blog page or a website, giving the writer the freedom to edit and update it according to the time. Articles being long, once written cannot be changed again.

A blog goes through very minimal straight forward, simple editing, while on the other hand articles are edited meticulously making sure to avoid any type of error whether its grammar or facts. Articles are usually published in a journal or magazine, hence editing is very crucial here.

SEO perspective:

To speak in a more digital point of view, a blog would help you create a more authoritative status and build leads for your business. It will serve an important purpose of building your SEO ranking by strategically including keywords, several links to serve the purpose and keep the visitors on the site for as long as possible.

On the other hand the objective of an article is to provide the necessary topic information in full description and don’t emphasize the keywords required for SEO. Being written in an extended format and published in journals, the use of keywords is not a crucial part of an article.

The final showdown

So the above are some of the crucial differences between a blog and an article to help writers to target their audience more effectively. Keeping that aside both blogging and article writing are extremely important for any business to create additional awareness for their brand and there is no reason a website can’t contain both. After all CONTENT IS KING! Now that you know the difference, let’s get cracking and get the increased traffic you are looking for!

May, 2020

Breakthrough: 2003 SARS survivor antibody, a potential cure for COVID-19.

With the number of COVID-19 cases surpassing 4.3 million worldwide and counting, scientists are working around the clock in efforts to develop vaccines and treatments to slow the pandemic. Currently, scientists are looking into whether existing drugs might work or whether new treatments need to be developed to try and tackle the virus.

In this article, we discuss the latest scientific finding, how an antibody identified in a survivor of the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak has the potential to neutralize COVID-19, providing a glimmer of hope in this current battle.

How do these antibodies work against COVID-19?

Development of immunity to a pathogen through natural infection is usually a multi-step process taking around 1-2 weeks. The body immediately reacts to fight the infection with a nonspecific innate response which will slow the progress of the virus and may even prevent it from causing symptoms. This is then followed by an adaptive response where the body produces antibodies specifically binding to the virus and eliminate it along with the cells infected.

Recently a research team came forward and publisher a paper stating that they have identified an antibody from a patient recovered from SARS 2003, which can potentially inhibit the cause of COVID-19. The antibody S309 is now on a fast track development and testing at Vir Biotechnology.

The scientists first identified monoclonal antibodies from the memory B cells of the SARS survivor. The memory B cells reproduce cells and have a long lineage, sometimes for life. The cells have the tendency to remember a pathogen or one similar to it and have the potential to fight against it in the future if re-infected.

The S309 antibody, in particular, is directed at a protein structure of the coronaviruses. The structure is essential for the virus, to recognize a host cell receptor and infect it. This particular infectivity capability is present in the spikes that crown the virus. S309, in particular, attacks the spike- disabling it, hence hindering the coronavirus to enter the cells. It should also be noted that the antibody showed the capability to target binding sites of several sarbocoviruses, not just COVID-19 and SARS.

What next- Will this be the breakthrough we all are hoping for COVID-19?

In this paper titled “Cross-neutralization of SARS-CoV and SARS-CoV2 by a human monoclonal antibody”, scientists have reported that by combining the S309 antibody with other similar antibodies identified in the recovered SARS survivor, there is a chance of neutralizing the COVID-19 virus. This cocktail of antibodies could be the answer to limit the coronavirus from forming mutants capable of escaping the single ingredient antibody.

“We still need to show that this antibody is protective in living systems, which has not yet been done,” said David Veesler senior author. “Right now there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19”, he added.

At this point in the pandemic, there is not enough evidence to prove the effect of antibody-mediated immunity against the virus. It cannot guarantee an immunity passport or a risk-free certificate. Further research and studies need to be performed before we can reach a conclusion.

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May, 2020

T-cells can play a crucial role in combating COVID-19

The only thing that is keeping researchers across the globe on their toes is the present pandemic situation. The scientists are working hard to find out a potential solution that can help fight the menace. Looking at this, they are exploring the known immune warriors in the human system, one of them is T- cell. Though known for fighting various viruses, the understanding of how T cells interact and fight against Sars-CoV2 is yet not clear. Recently, two studies suggest that patients infected with COVID harbor T-cells to target viruses that might have helped them in recovery. The study reveals that some of the people already have these cellular defense mechanisms mostly because they have a history of infection with any of the coronaviruses.

“This is encouraging data,” says virologist Angela Rasmussen of Columbia University. Although the studies don’t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which “bodes well for the development of long-term protective immunity,” Rasmussen says. The findings of the research study can help scientists come up with a potential vaccine candidate.

“One reason that a large chunk of the population may be able to deal with the virus is that we may have some small residual immunity from our exposure to common cold viruses,” says viral immunologist Steven Varga of the University of Iowa.

Presently, most of the vaccine candidates are developed by targeting the other component of the immune system. For example, many biotech companies are coming up with antibodies based vaccines which are mainly made by B-cells when they interact with the virus. Whereas the T-cell based mechanism differs a little. There are two different mechanisms that define the working of T-cells. One way is where helper T-cells interact with other biological components like B-cells, interleukins, and more to put them into action against the virus. The second way is where killer T-cells directly recognize and target the virus to destroy them from the site. This is the reason that the severity of disease among different patients varies depending upon how strong their Tcell response is.

The scientist team used some bioinformatics tools to assess the interaction between the viral protein and Tcell. For this, they exposed immune cells of few patients to the viral spikes, who have recovered fro the COVID infection. The results showed that all patients harbored helper T cells that helped in the recognition of viral spike protein. This spike protein plays a crucial role while invading a cell. The team also identified killer T0cells in almost 70% of patients, as reported in the ‘Cell’. “The immune system sees this virus and mounts an effective immune response,” says the researcher.

“It is encouraging that we are seeing good helper T cell responses against SARS-CoV-2 in COVID-19 cases,” says a researcher involved in the study.

The present study highlights the importance of looking at other potential immune mechanisms to target COVID-19. Moreover, understanding the detailed role of T-cell in the fight against the virus can have significant implications in the development of potential vaccine candidates. The study has come on time to help researchers find ways to implement it and develop a therapy that can help in turning down the pandemic.

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May, 2020

Coronavirus can spread through sewage systems, say experts

While the phrase may start to sound cliche, it still rings true! These are truly unparalleled times. The past few weeks have been nothing short of an immense change for all of us, leading us to adapt and change our lives and businesses to deal with the COVID-19 outbreak.

With the lockdown being lifted in several countries, health officials all over the world are broadening the search for the people infected and focusing on slowing the spread. This includes finding all possible sources through which the virus can spread. When the response to the pandemic has been focused mostly on preventing community spread, Professor Quilliam and colleagues at the University of Stirling, recently released a paper warning that sewage system can play as a potential COVID-19 transmission risk and that it must not be neglected in this battle to protect human health.

Can COVID-19 really survive in human feces or sewer systems? POSSIBLY.

With years of studying the transport of bacteria in various marine environments, Professor Quilliam stated that “We know that COVID-19 is spread through droplets from coughs and sneezes, or via objects or materials that carry infection. However, it has recently been confirmed that the virus can also be found in human feces – up to 33 days after the patient has tested negative for the respiratory symptoms of COVID-19″.

The authors explained that given the structure of COVID-19, specifically its lipid envelope covering, makes its behavior unpredictable in different aqueous situations. Though the information on COVID-19 environmental persistence is limited, from previous research it should be noted that other coronaviruses have known to survive in viable sewage for around 14 days.

Should wastewater treatment plant operators take extra precautions? YES, BE SAFE!

The authors further added that there is a good possibility for the virus to aerosolize, particularly during the pumping and transfer of wastewater through different sewer systems. This could lead to atmospheric loading of the virus in the form of water droplets, giving it direct access to the respiratory tract of the people exposed. It must be acknowledged that people working at the sewage pumping stations or wastewater treatments are more at risk and need to be provided protective equipment. They must also be educated to seek medical care when showing any signs or symptoms.

Areas with open sewage systems, especially in developing countries and places where safely managed sanitation systems are limited are high at risk. The authors further added that “Such settings are commonly accompanied by poorly resourced and fragile healthcare systems, thus amplifying both exposure risk and potential mortality,”

Is this finding a possible breakthrough? MAYBE, MAYBE NOT.

The authors stated that “It is not yet known whether the virus can be transmitted via the fecal-oral route, however, we know that viral shedding from the digestive system can last longer than shedding from the respiratory tract. Therefore, this could be important – but as yet unquantified – a pathway for increased exposure.”

As the limited number of adequate testing in many places has made it difficult to keep pace with the quick-spreading virus, scientists believe that monitoring sewage for the virus will provide a cheap and reliable alternative. The experts further added that this removes the guesswork about when to impose local lockdowns — or when to lift them.

Though an interesting way to keep track of the virus, monitoring wastewater for the said virus is hardly an easy task. The approach poses many challenges, including deploying it on a large scale and winning the government’s approval.

The authors concluded the paper by stating that In the immediate future, there needs to be an investment of resources to improve our understanding of the risks associated with the fecal transmission of SARS-CoV-2 and whether this respiratory virus can be disseminated by enteric transmission.

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Should wastewater treatment plant operators take extra precautions? YES, BE SAFE!