#PositiveCorona : “Don’t feel depressed before being actually into it”- Positive thinking is an important survival strategy for today’s world.

Student Contributor: Debjani Gupta, B.Sc. 1st Year Biotechnology.

Ever wondered why everything does not work in a way that we think or plan? Why it does affect us so much? The most paramount ground is our fragmentary philosophical sense. We often lack comprehensive relevant thoughts that restrict us from extensive rational thinking. We plan out the events the way that pleases us and then followed by our theory about the sequences of action. All of that happens on a faster time scale, and then it becomes very difficult to judge whether our choice of action is virtual or lack sense.

Our brain cells share different kinds of information using a variety of brain waves, analogous to the way radio stations broadcast on different frequencies. The way we take things inside the brain, it has an adjacent way of publishing it.

Depression, it just a stain that is native to ignorance, preconception, and distress creating a great complication in life and moulding out a state where we often choose to suffer mental agony and undergo adverse stress. It is such a crippling affliction of the nervous system which affects our thinking pattern and how we feel or react to any situation. It is not just only a feeling of dejection but also takes away our will to live. In a way injuring our hypothetical backbone of self-control and resolution towards life. It is just a game played by our nerve cell connection and unfortunately, it wins, but only then when we assist in it. We need to be strong enough to defend ourselves against our uncooperative notions.

“In sooth, I know not why I am so sad: It wearies me; you say it wearies you; But how I caught it, found it, or came by it, What stuff ’tis made of, whereof it is born, I am to learn, And such a want-wit sadness makes of me, That I have much ado to know myself.” He says he does not know why he is depressed. This famous quote by William Shakespeare has so relevant in today’s world and even in this 21st century, we are unable or fail to notice our cause of desolation?

Well, when we look through the science behind depression, a chemical imbalance may not be the only reason, rather also the fault in controlling our mood, unshielded genetic problems, medical problems and most importantly stressful pressurized life also play a severe role in the creation of this deadly devil, i.e. depression. Emotions and mood are just like friends in demand and calls each other as a helping hand. Emotions decide our mood and mood decides our state of mind. The mood is typically regulated in brain and research suggests that depression is an impact of mood and that the nerve cells connection and their functioning have a great influence on depression.

Our mental condition gets restricted or compressed just similar to what happens in a computer when a file is compressed and then store. Just like digital compression, when we try to assemble all our memories and thoughts and things happen in life or we try to imagine the upcoming consequences, then that becomes very perplexing and dreadful. A compressed file always has less reach than the details found in the source material.

Brain cells produce an extended degree of neurotransmitters that regulates our sense, memory, and also a fine-tuner regulating our mood. The oversensitive or insensitive receptors adjust the release of neurotransmitters. There is also the influence of genetic and hereditary contribution that causes depression.

But all of it starts when we fail to challenge and confront our own gloomy and contradictory feelings that clench and seize us from all possible ways and snatches all our power and will to defend and fight in such a depressing situation. In these dire circumstances, the most important thing to think about is not to think too much about depression. Feeling depressed before being actually into it, makes oneself more prone and victim to it and imposing a step ahead of it. So, the only way out of this deadly slow-progressing psychological situation is to practice Positive thinking. Now, the most relevant question to us or to everyone what we mean by Positive thinking?  It is an attitude to train your mind to develop a positive outlook to any or every kind of problem we face in our daily life, it does not make any difference that whether the situation is favorable or not, but we need to develop our basic thinking in such a way that we can only expect or hope for the betterment and try to focus on the good in any given situation. It has been already proven by several studies that positive thinking plays a crucial role in improving both mental and physical health. We always need to remind ourselves that this situation will no longer stay forever and “this too shall pass”. It is one of the kinds of fight back mechanisms, we need to practice to combat any unpleasant situation, which may be one of the survival strategies for today’s world and we always need to remember this particular famous quote….

“According to Darwin’s Origin of Species, it is not the most intellectual of the species that survives; it is not the strongest that survives; but the species that survives is the one that is able best to adapt and adjust to the changing environment in which it finds itself.”

and that adaptation is positive thinking in this ever-changing world. It is the best adjustment that one can do in this situation. So, be always positive and think optimistic.

The utility of Biomarkers Against COVID-19

Student Contributors: Ankita Mallick & Manidipa Roy, B.Tech. Biotechnology, 2nd Year

Appreciation of biology against COVID-19:

COVID-19 highlighted the importance of biology in the field of biotechnology. It’s amazing to see how biotech companies of all sizes have put aside their primary products to shift and try to tackle coronavirus from all different angles, from therapeutics and antivirals to new types of diagnostic kits. In the current scenario, Biotechnologists are all trying to think through this COVID problem from their vantage point and seeing how quickly they can reduce this global issue by choosing an appropriate platform and switch it up to hopefully make it successful against this global pandemic disaster. One of the recent findings is the discovery of some biomarkers and their use in understanding the disease perfectly.

Biomarkers Helping to understand the mortality of COVID-19 patients:

  • The increasing rate of COVID-19 cases forced healthcare systems globally to make an early clinical set-up that can reduce the world’s mortality rate to some extent. Based on this pressure, the Wuhan region of China collected 485 blood samples from the positive COVID-19 patients, in search of active biomarkers that can predict the mortality rate for an infected person. Following this task, clinical machine tools confirmed three crucial biomarkers that primarily can give a clear idea of the mortality rate with an appropriate 90% fine accuracy. These three biomarkers include Lactate dehydrogenase (LDH), lymphocyte, and high-sensitivity-C Reactive protein (hs-CRP).
  • The increased amount of LDH alone play a major role that can differentiate those case that requires quick clinical importance. It has been fascinating to note that this high extent of LDH level could be correlated with high levels of tissue damages and breakdown and this is also evident in many different diseases, one of them includes pulmonary disorders such as pneumonia. Algorithms based mathematical machine model was developed for the identification purposes of these biomarkers.
  • For the sharpness of idiopathic pulmonary fibrosis, serum LDH plays a crucial role as a biomarker. Hence the high measure of LDH indicates lung injury & is the most significant primary marker for pulmonary interstitial diseased patients. So, the rise in LDH range correlates with the seriousness of infection in COVID-19 patients, give a clear sign of lung injury as well as indicating mortality rate at risk.
  • The second biomarker is hs-CRP. The high extent of hs-CRP serves as a marker for poor clinical outlook in case of acute respiratory distress syndrome, which highlights the continual state of inflammation. Following this state of inflammation, the result is large grey-white lesions appear in the lungs of COVID-19 patients. A higher quantity of gummed secretion had also been noticed in the tissue section that over flooded from the alveoli.
  • Lastly, the third biomarker lymphocytes can be used as a possible choice for healing or therapeutic purposes. Clinical studies give evidence to this hypothesis. COVID-19 patients are also frequently associated with lymphopenia, which is a major risk in the case of mortality. The persistent state of lymphopenia seen in SARS-CoV-2 and also in MERS-CoV patients, due to the infiltration of lymphocytes caused by the injured alveolar epithelial cells. The most significant feature of COVID-19 is lymphopenia which is also associated with decreased count of CD4 & CD8T cells. So, in the prediction of mortality rate, lymphocytes again could play a significant role in determining the course of these particular diseases. Thus, researchers keen to take this area for further scientific investigation.

So, it can be concluded that these three specific biomarkers could be useful to predict the course of COVID-19 infection and also the associated medical complications in seriously ill patients. Thus, these clinical markers have proven to be helpful to enable the health care systems of go for early detection of the mortality rate of every single COVID-19 patient, so based on that the higher risk group can be identified easily and quickly for immediate medical attention, which in turn can decrease the rate of mortality among individuals.

Is COVID-19 more fatal than we perceived till now besides being a severe breathing disease?

Student Contributors: Koustav Kiran Das (B.Sc. 3rd Year), Sampurna Nandi (B.Tech. 2nd Year).

COVID 19 has become the most used jargon in recent times due to its huge impact on the daily lives of humankind worldwide. SARS-CoV-2 i.e. Severe Acute Respiratory Syndrome Coronavirus 2019, the virus responsible for COVID 19, emerged in Wuhan, China in 2019, and rapidly spread all over the world. The most characteristic clinical symptoms of this particular disease are respiratory distress and spontaneous breathing incapability, along with other symptoms. Some patients with this viral disease also exhibited some neurological signs and symptoms such as headache, nausea, and vomiting. Moreover, it has also been reported by various scientific groups that this virus is not always restricted it’s spreading only to the respiratory tract, moreover, it can also conquer it’s viral propagation into the CNS i.e. Central Nervous System, inducing a wide range of neurological problems.

Some Scientific Facts:

  • Genomic analysis shows that the virus responsible for COVID-19, i.e. SARS-CoV-2 is related to other beta-coronaviruses like MERS-CoV (Middle East Respiratory Syndrome Coronavirus) and SARS-CoV, and it shares high homology with SARS-CoV.
  • The entry of SARS-CoV-2 into its host cells i.e. human cells has been associated with the same receptors like SARS-CoV.
  • Surprisingly, it has been reported that most coronaviruses have very similar kinds of structural features and they also employ a very common infection pathway, and therefore the infection mechanisms previously reported for other coronaviruses, may be relevant for SARS-CoV-2 also.
  • SARS-CoV-2 enters the human host cells by a cellular receptor Angiotensin-Converting Enzyme 2 (ACE2), it is an enzyme which is present in various groups of cells and organs such as cells on the alveolar surface, cells on the intestinal wall, the inner lining of arterial and venous cells and also in cells of skeletal muscles and vascular cells of Brain and nervous system.
  • This enzyme acts as a protecting factor in these organs and regulates blood pressure and prevents the build-up of plaque in the arterial walls. However, this enzyme is also a target for various coronaviruses.
  • In addition to this, the virus can also enter the CNS via the olfactory nerve, the nerve that leads to the brain from the nasal cavity.
  • A study on Covid-19 patients recently found that along with severe breathing troubles, some other neurological symptoms also manifested, including headaches, disturbed consciousness, and burning sensation in hands, arms, or legs. This list also includes ischemic and hemorrhage type strokes.

So from these scientific facts, it can be easily suggested that there is a strong correlation been observed between COVID 19 infection and other neurological diseases, which need to be addressed immediately by our medical professionals and scientists. Keeping in mind the neurological cases arising in the wake of the CoViD-19 pandemic, the presence  of Neurologists at the frontline have now become extremely important to assess the clinical situations. Moreover, it is imperative to note that other neurological diseases could also occur due to COVID-19 infection and which is very alarming. So, here is a small list of some other neurological diseases caused by this deadly virus.

Other Neurological Infections that could be caused by SARS-CoV-2

  • Viral encephalitis: Infections in CNS; lesions in the brain and nervous tissue and neuronal damage. Symptoms include headache, high fever, vomiting, epilepsy, and consciousness disturbances.
  • Infectious toxic encephalopathy: A reversible brain dysfunction syndrome led by systemic toxemia (toxins produced by body cells due to infection), metabolic disorders, hypoxia (deprival of oxygen in the body), and cerebral edema (swelling of the brain). Symptoms include mild headache, mental disorder, mental confusion, emotional disruption, thinking disability to serious loss of consciousness, mental disorientation, coma, and paralysis.
  • Acute Cerebrovascular disease: Breathing related infection is an independent risk factor for cerebrovascular disease. Symptoms include ischemic brain injury and cerebral hemorrhage due to cytokine storm. It also causes elevated levels of D-dimers in severely infected patients with severe platelet reduction too.

Is convalescent plasma therapy being a new cure for COVID-19?

Student Contributors: Aman Dafadar & Rani Kumari (B.Sc. Biotechnology 3rd Year)

COVID-19 is a highly contagious disease affecting more than 24 lacs individuals worldwide. The disease is mainly caused by a novel coronavirus, SARS-CoV-2. The disease is highly infectious and reportedly infects older people with a higher frequency. The virus mainly spread through respiratory droplets, produced during sneezing or coughing by an infected individual. It is one of the new types of coronavirus, which is only a few months old. So, we know very little about this particular virus. But unfortunately, this virus already claimed more than 1.7 lacs lives worldwide. From the very first day of this viral infection, it has been opened out like a turmoil that is being very challenging to control. The medical professionals and scientists are giving the best of themselves to put this to an end. As the emerging cases are rising robustly throughout the world, researchers and doctors are considering convalescent plasma as one of the best approaches to treat COVID-19 patients at present. Moreover, convalescent plasma has been a promising strategy for many infectious diseases in the past including the 1918-Spanish flu pandemic, Ebola, 2003-SARS, 2009-10- influenza virus pandemic,2012 MERS-CoV epidemic, and many other diseases. Now the first question which comes to our mind is

What is convalescent plasma therapy?

Convalescent plasma is also known as the convalescent serum is the serum collected from a patient who has recovered an infectious disease and contains an antibody against that disease. Antibodies are certain molecules, produced by our system when we encounter certain pathogens, like viruses, bacteria, etc. Convalescent plasma is being used since the 1880s to treat many viral and bacterial infections. In this therapy antibodies from the blood plasma of the recovered patient are transfused into a sick patient suffering from the same disease.

So from the above-mentioned text, we have an idea of Convalescent plasma therapy, but then the second question should be how this particular line of therapy could be useful to control this current pandemic and how does this particular therapy work?

How does it work?

Individuals recovering from COVID-19 have neutralizing antibodies against the virus and injecting these antibodies into a patient suffering from the disease will boost the immune response and can lower the period of symptoms and severity of the disease.

Blood (about 600-800 ml) is extracted from the donor (i.e. recovered patient) and is screened for any possible pathogen if it is devoid of any other potential pathogen, then the plasma portion is separated from the blood through a very small instrument, and is eventually transfused to the patient suffering from COVID-19.

But, to be a donor, a person needs to qualify a few standards. They have to be tested positive for COVID-19 and recovered fully having no symptoms for 14 days and also the donor and patient should be of compatible blood types. Moreover, it has been interesting to note that a single donor produces enough plasma to treat two to three patients.

Though China has been claiming to get positive results of convalescent plasma treatments on the patients of COVID-19, the treatment is still considered under clinical trials and there are no specific results on the betterment of treated patients as well as no routine protocols on what amount of convalescent plasma and how often it can and should be used. According to some researchers, this technique is rather a preventive measure and not the actual treatment. But since we do not have any other therapeutic way to prevent this deadly pathogen, convalescent plasma therapy could be one of the treatment procedures to at least save a few lives.

Why plasma?

Plasma is the largest component of blood suspended with RBCs, WBCs, and Platelets. Plasma is about 92% water, salt, and enzymes, human plasma also contains important components such as immunoglobulin, albumin, and fibrinogen. Plasma mainly transports protein, hormones, and nutrients to the cells in our body. The plasma is rich in blood components like antibodies and protein it is used in therapies like Convalescent plasma, PRP(Platelet Rich Plasma), Plasmapheresis, Fresh Frozen Plasma.

After China and the USA, many states of India have also started the clinical trials of treating COVID-19 by convalescent plasma, and due to the past success rates of this therapy, it has opened a window of hope for the world in this crucial scenario.

COVID-19: Present remedies and link to Air Pollution

Student Contributor: Soham Biswas

In December 2019, while the Christmas Eve was approaching near, several patients in the Wuhan district of China were diagnosed with ruthless pneumonia caused by an unknown virus. In response, an epidemiological alert was placed by the World Health Organization (WHO) on December 31, 2019.

By January 7, 2020, Chinese scientists had isolated the causative agent and named the virus as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a few months that followed, the virus spread its cruelty across far-off countries resulting in the present-day infamous pandemic situation of the coronavirus disease 2019 (COVID-19). No doubt, it is one of the most desperate situations that the world has seen in recent times as many of the countries face a complete lockdown. About 80% of the patients remain asymptomatic being only the carrier of the disease and mostly remain undetected. So, the virus could infect more and more people while causing deaths of the more vulnerable ones. It has been observed that most susceptible ones are the old age people, the ones with the compromised immune system and pre-existing respiratory ailments, the new-borns and the expected mothers. It has also been found that the immune system of patients with SARS-CoV-2 infection gets drastically affected as the surviving T-cells are functionally exhausted, suggesting that, they are at potential risk of developing secondary infections that cannot occur if the immune system is strong and healthy. With a mortality rate of less than 7% the virus has already claimed 1.4 lakh lives worldwide and infected more than 20 lakhs within just five months of its outbreak recorded to date. But unfortunately, this is not the actual number, since the number of tests done to detect the disease is much less in most of the countries. Therefore, the actual number of the unlucky people infected with this RNA virus could be much larger and this points a serious concern.

No one in their wildest imagination could have ever thought that someday a mutant flu virus would cage them in their homes and make them go to banks and markets while dressing like a robber, such as the dramatic impact of the COVID-19. According to a recent study, it has been observed that air pollution could be an important issue in the enhanced severity of the infection. It has been proposed that prolonged exposure to air pollution could impair the first line of defense of upper airways, such individuals are at a higher risk of developing acute respiratory disease syndromes(ARDS). They are much more vulnerable to being invaded by the virus as it could easily surpass the already weakened upper respiratory defenses while reaching the lower airways. In that case, it would cause a heavy toll on the already weakened immune system and the effect could be fatal. Since the modification of the immune system had taken place through prolonged exposure to pollution therefore short term improvement in air quality would not improve the immune power of individuals. This might be the case of Lombardy and Emilia Romagna of northern Italy, which were the two most polluted areas of Europe. Despite, the drastic reduction in pollution the mortality rates due to infection has not quite lowered there. Perhaps the first lesson to counter the pandemic should be to lower the pollution and live in complete harmony with nature. Though nothing is proved yet, air pollution could be a cause that will increase the death rate of this particular infection.

        To combat this dire situation, our valiant battalions of scientists and doctors, have launched large scale research at the frontlines to quickly find out a remedy to the disease. Right now there is no available drug or vaccine that is present to fight against this deadly virus. So, repurposing of existing various drugs could be a successful alternative to counter the disease since the time is very short and the development of a particular vaccine would take a longer time.

Many compounds have been found to have a probable clinical advantage against the virus. Notable among them, are:

  • Chloroquine and Hydroxychloroquineare the compounds that prevent the generation of inflammatory signals. Biochemically, it interferes with the interaction of the toll-like receptor(TLR)  and the mature virion and prevents the cytokine production.

 

  • Oseltamivir is a neuraminidase inhibitor that is thought to disrupt the virus-host cell interaction. In India, it is already prescribed to patients suspected to have COVID-19 and are already displaying mild symptoms like low-grade fever, cough, malaise, rhinorrhea, sore throat without shortness of breath.

 

  • Arbidol (Umifenovir) has shown a promising inhibitory effect in lowering the reproduction rate of the virus in vitro. Currently, this drug is under phase 4 clinical trial.

 

  • Ribavirin prevents the replication of RNA virus by acting as a nucleoside analog and suppressing the activity of inosine monophosphate dehydrogenase which in turn downregulates the synthesis of guanosine triphosphate (GTP). Ribavirin had been widely used to treat SARS patients in Hong Kong. Thus, it could be a possible option for COVID-19 treatment.

 

  • Ritonavir and Lopinavir have been found to bind to the proteinase 3CL-pro of the SARS-CoV-2 that cleaves the polyprotein at 11sites from the C-terminus and inhibits its function, thereby disrupting protein expression. Thus is a promising drug that could be used often in combination with other drugs.

 

  • Darunavir and Cobicistat are HIV protease inhibitors. Currently under the phase 3 clinical trial.

 

  • ASC09F is also an HIV inhibitor currently under phase 3 clinical trial in combination with Oseltamivir.

Remdesivirand Favipiravirare Inhibitors of RNA polymerase hence thought to be used against the SARS-CoV-2 which is an RNA virus.

Apart from these compounds, with the help of bioinformatics analysis, a compound namedBaricitinib has been identified to be helpful as it could inhibit the enzyme AP-2-associated protein kinase 1 (AAK1) that plays an important role in the cellular entry of the virus. Another compound camostat mesylate, that inhibits the enzyme TMPRSS2 that is involved in the maturation of the spike protein on the virion could also be helpful. By using the principles of RDT a soluble recombinant ACE2 protein has been designed that could competitively bind to the virus and prevent its binding to the membrane-anchored version of the receptor. This innovation has worked well in vitro and monkey models and could perhaps effectively combat the disease.  Antiviral therapy using the Interferon-alpha (IFNα) also looks promising as it could directly interfere with the viral replication and prevent its spread. Tocilizumab, an inhibitor of interleukin 6 is also reported to be useful in severe cases of COVID-19 with elevated IL-6.

Certain Chinese traditional medicine has also surfaced as a potential means to treat the pandemic and is consequently being investigated. Notable, among them, are:

  • Glycyrrhizin, an active component of licorice roots that could competitively bind to ACE2 and also efficiently disrupted the replication of SARS-CoV-2 in-vitro.
  • Baicalin, isolated from Scutellaria baicalensis the famous Chinese skullcap, is a flavone that has exhibited certain antiviral activity.
  • Quercetin, another compound has been reported to exert antiviral activity by blocking host cell entry and disrupting the action of  the viral protienase 3CLpro.
  • Hesperetin, a compound isolated from citrus fruits inhibits the cleavage activity of the 3C-like protease (3CLpro).

Apart, from these Chinese ‘nuskhas’, different immunotherapeutic approaches are also being taken. One of these is Convalescent plasma therapy, where the convalescent plasma of the recovered patient is used to treat the newly infected has been started.

Though we do not have any scientifically recommended remedy to this particular disease right now, there are many current possibilities to counter the virus and we can hope that the battle won’t last long for it is just a matter of time, when we would have our perfect remedy and then just like in every era we would emerge victorious in the race of the survival of the fittest.

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