Monoclonal antibody treatment for Covid-19

Monoclonal antibody

They are the lab made protein, mimicking the natural immune system of the human body, to fight any infection like SARS-CoV-2. It is advised as to avoid hospitalization while being found with the positive Covid test.

Restrictions

It is restricted to people of 65 or more years in age. So fairly the Covid-19 patients are always asked to get tested quickly and then get advise for the treatment of monoclonal antibody infusion.

FDA has also now advised for the monoclonal antibody treatment for SARS-CoV-2 in a recent FDA news release. One can see the list of qualification for the Monoclonal antibody treatment on certain website of hospital.

More recommendations

"It's the best treatment we have to keep you out of the hospital. It keeps people out of the hospital 70 percent of the time," said Montgomery-area pulmonologist Dr. David Thrasher. "It's really a great treatment and everybody needs to ask for it."

The fifth nucleobase

Basic ingredient in genetic recipe

Four letter A,T,C,G of genetic alphabet forming three letter words (codon), specifying for 20 amino acids, makes the basic molecular foundation of all life forms. 

But some viruses show a fundamental genomic change, a modified novel fifth base in nucleotide.

Z genome with a noncanonical modified base

In a strategy to escape bacterial restriction enzyme, it was found in the genome of  200 phage virus like one as cyanophage S-2L, out of the four canonical Watson-Crick nucleobases A,T,C,G; A is replaced by the diaminopurine (Z) forming three hydrogen bonds with T, which makes it more stable and rigid from bacterial defenses than double bond A=T. It was first reported in 1977 by soviet researcher. Further study suggest that aminoadenine in place of adenine was included in the phylogeny of these bacteriophage since archaic.

Jordana Cepelewicz in her article further states that: 'Z and other modified DNA bases seem to have evolve to help viruses evade the defenses with which bacteria degrade foreign genetic material. The eternal arms race between bacteriophages and their host cells probably provides enough selection pressure to affect something as seemingly "sacrosanct" as DNA, according to Romesberg.'

Fear memories and neuronal disorders

Rapid gene expression and DSBs

In a research study, it was found that the neuronal activity induced DNA double strand breaks (DSBs) to cause a change in neuronal activity regulated genes, when an organism is exposed to new sensory experience due to change in organism's external environment. That is a process of quick access to store genetic instructions as store memories.

Neuronal damage

But Li-Huei Tsai, the Picower professor of neuroscience found in her lab studies that fear memories induced repeated DSBs causes severe neuronal damage results neurological diseases causing neurodegenerative disorders impacting learning and memories. As routinely repair process of breaks become flawed and fragile with age, as repair mechanism falters.

In a research article Aging brain initiative, Tsai says, "We wanted to understand exactly how widespread and extensive this natural activity is in the brain upon memory formation because that can give us insight into how genomic instability could undermine brain health down the road," "Clearly, memory formation is an urgent priority for healthy brain function, but these new results showing that several types of brain cells (including Glia called astrocytes), break their DNA in so many places to quickly express genes is still striking." It was found that Glia DSBs response to hormone glutocorticoids, secreted in response of stress in fear conditioning, shows robust transcriptional response of glia to stress through hormone.

Brain sites of fear memories 

Author in their study found that creation of fear memories doubled the number of DSBs in variety of cell types in prefrontal cortex and hippocampus regions essential for formation and storage of conditioned fear memories, affecting more than 300 genes in each region for making synaptic connections due increased transcriptionally induced loci, a phenomenon called 'synaptic plasticity'. So such new groups of neurons connected together cause formation of new memories, called engrams. 

 

Damages due to frequent DSBs

The researchers wrote, 'Overall we have identified sites of DSBs at genes important for neuronal and glial functions, suggesting that impaired DNA repair of these recurrent DNA breaks which are generated as part of brain activity could result in genomic instability that contribute to aging and disease in the brain'.

*This blog is inspired by the MIT news from Picower institute for learning and memory. Many more research paper links are also thankfully inserted in blog, from public domain publication for detail study if needs. Graphic is by blog author.

Father of nuclear bomb and Sanskrit scripture Bhagavat-Gita

"I have always been curious to know the inspiration behind those brains of key nuclear physicist, working in the 'Manhattan Project' in 1945, resulting in nuclear bomb then code named 'Gadget'.

And here comes a book, from the 'Hindu' scripture 'Bhagavat-Gita', which 'Oppenheimer' quoted before and after the 'Trinity test', many a time.

Hard it is to conclude if the 'Gita' was/is a book inspiring for a decisive fight against enemy or a truce resulting after the war of such a ferocious magnitude.

What an irony, the war referred in this scripture was finally fought with 'Brahmastra', a name in 'Sanskrit', believed to be a nuclear weapon of that time." 

--Author 

(Storyline: J. Robert Oppenheimer/ Nuclear bomb/ Inspiration/ Bhagavat-Gita/ Indology)

July 16th:

Every year this date reminds us about first nuclear detonation, code named 'Trinity' (assigned by Oppenheimer), tested successfully in 1945 on the culmination of 'Manhattan Project' which later used against humans in shorter than a month time, i.e. 6th August 1945 on Hiroshima, killing 126,000 civilians instantly.

It is recorded that more than 130,000 strong human force were employed in this Nuclear weapon research project, secretly conducted at various sites in US, Canada and UK, in the World War II years ranging from 1942 to 1946.

What an irony:

1. The German chemists were the pioneer scientist namely Otto Hahn and Fritz Strassmann discovering Nuclear fission which theoretically explained by Lise Meitner and Otto Frisch. 

But it was the party opposite to use this technology to win and end the second world war lastly.

2. Those who were involved in the Project may not be knowing the full impact of destruction it was going to cause and whole concept of war and peace was going to change there on.

3. It is said that two days before the 'Trinity' test, Oppenheimer expressed his hope and fear by citing a quote from the Hindu scripture Bhagavat-Gita, as: "In battle, In the forest, at the precipice in the mountains, On the dark great sea, in the midst of javelins and arrows, In sleep, in confusion, in the depths of shame, The good deeds a man has done before defend him."

4. Later in 2016 US President Barack Obama was in Hiroshima, recalled; "Death fell from the sky and the world was changed" where 80,000 lives were lost instantly on 9th August 1945 as the second Nuclear bomb was dropped over Japan.

That reminds the warning wordings of then President Truman saying, "expect a rain of ruin from the air, the like of which has never been seen on this earth."

Julius Robert Oppenheimer: (Physicist and Professor at the University of California Berkeley)
Oppie, as his friends called him, the war time head of the Los Alamos laboratory, was among many who worked in the 'Manhattan Project', he is the one credited as the 'Father of the Atomic bomb.'

While witnessing the 'Trinity' explosion he thought about a verse from a Hindu scripture Bhagvat Gita (XI, 12): "If the radiance of a thousand suns were to burst at once into the sky, that would be like the splendor of the mighty one.."

His Gita connection: 

It was way back in 1933, much before the 'Manhattan Project', Oppenheimer, a Jewish by birth, learned Sanskrit from an Indologist, Professor Arthur W. Ryder at Berkeley, read Gita in Sanskrit. Later he recalled that this was the book that shaped his philosophy of life.

Oppenheimer persuaded to quote again for a television broadcast in 1965:
"We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita (verse 32 of chapter 11). Vishnu is trying to persuade the Prince that he should do his duty, and, to impress him, takes on his multi-armed form and says, 'Now I am become death, the destroyer of worlds.' I suppose we all thought that, one way or another."

Link for text, translated-audio, Oppenheimer's video:
http://www.bhagavad-gita.org/Gita/verse-11-30.html

'Bhagvat-Gita' scripture showing page with a verse 11-30, with an English translation by Oppenheimer, which is being quoted more often.

Life after: 

As quoted by author Robert Monk in his book, Oppenheimer reportedly told the then President Truman on October 25, 1945: "Mr.President, I feel I have blood on my hands."

Such was the sorrow !

it enveloped everyone !! 

even those who created it !!!

*A related article by the author:

Hiroshima, Nagasaki in ethical perspective of nuclear bomb creator

Hiroshima, Nagasaki in ethical perspective of nuclear bomb creator

"Out of curiosity, I have always thought about the minds of scientists working 76 years back in 'Manhattan project' then in 1948 and whose labor was materialized in less than a month time after 'Trinity' test, into a man hunting arsenal causing massacre at large in Hiroshima and Nagasaki on 6th and 9th August 1945, culminating into the last bloodiest scar for humanity to remember for generations, if they do not learn any lesson from.

From their statements, some being quoted below for easy reference, one can easily conclude their utter frustration from this outcome with a collective sense of regret." 

--Author

(Storyline: Second world war/ Nuclear bomb/ Aesthetic and ethical judgement)

Life is lot more fragile than we think. So you should treat others in a way that leaves no regrets. Fairly, and if possible, sincerely. It's too easy not to make the effort, then weep and wring your hands after the person dies. 

--Haruki Murakami 

J. Robert Oppenheimer: 'We have made a very grave mistake', and 'in some sort of crude sense..the physicist have known sin.'

In a famous quote about his meet with President Henry Truman, he has said then, 'Mr. President, I feel I have blood on my hands.'
Well, then he was referring the future too.

Henry Wallace, then the Vice President, recalls about him in his diary, 'I never saw a man in such an extremely nervous state as Oppenheimer. He seemed to feel that the destruction of the entire human race was imminent.'

Later he vocalize his fear by saying, 'the people of this world must unite or they will perish.'

Reminiscing his earlier days while working in Los Alamos Laboratory, 'To me (the task at hand) is primarily the development in time of war of a military weapon of some consequences,....concern was as if to save the civilization.'

Perhaps when he referred through his famous quote of the Gita after the Trinity test:   'I am become death, the destroyer of the worlds,' ..was perhaps pointing his concern for humanity in posterity.

Albert Einstein: He did not play a direct role but his discoveries did and he was in regret for the letter he wrote to Roosevelt . 'Had I known that the Germans would not succeed in producing Atomic bomb', he said, 'I would have never lifted a finger.'

In 1954, 5 months before his death, he has said, 'I made one great mistake in my life ..when I signed the letter to President Roosevelt recommending that atom bombs be made.'

'Politics is more difficult than physics', was the answer of Albert Einstein when he was asked, why one can discover the atomic power and not to control it.

CRISPR-Cas9 gene editing tool can cause chromothripsis leading to oncogenes

CRISPER-Cas9 an ancient immune system in bacterium
Microbiologist in 1993 identified some unique repetitive, well preserved DNA sequences in Prokaryotes, appearing over and over again. Between repetitive  DNA sequences there are unique sequences that differs. These repetitive sequences are called as 'clustered regularly interspaced short palindromic repeats', abbreviated as CRISPER. Those non repetitive sequences matches with the genome of their pathogenic phage viruses. "So the hypothesis were put forward that bacterium succeeded in surviving from the virus infection by adding a piece of virus genetic code into it's genome as the memory of the infection. Perhaps the mechanism used by bacterium to neutralize a virus is by RNA interference." These were named as trans-activating crispr RNA (tracrRNA). That's an ancient immune system that protects bacterium from the infection of viruses.

Genetic scissor

Emmanuelle Charpentier and Jennifer Doudna, found that apart from CRISPER there are special CRISPER associated (cas9) genes, known for coding of a protein which unwinds and cleaves DNA (perhaps for the virus genetic material). Both scientists realized that the CRISPER-cas9 system could be programmed to cut other pieces of DNA and were awarded Nobel Prize 2020 in Chemistry "for the development of a method for genome editing". This precise molecular tool, like a scissor to make precise incision in DNA , to rewrite the code of life i.e. the genetic material.

Emmanuelle (left) and Jennifer (right)
Thankfully shared from Nobel Media in public domain

It also raises ethical, social and safety concerns as it's controversial use on human cells. This genetic scissor opened a new era of possibilities in the field of life sciences, biochemistry, cell biology, like as a gene editor, knowing the functions of genes and editing them for desired characters in plant breeding or controlling hereditary diseases etc.

CRISPER-Cas9 and genotoxicity

CRISPER-Cas9 based therapies have reported many genotoxic incident causing clinical complications like large scale DNA deletions, p53 tumor suppressor protein, chromosomal truncations, preexisting antibodies and T cells induced problems.

This happens because in clinical applications the possible safety concern and care are not being taken, resulting in break of d-DNA that results in genomic rearrangement, that means individual arrangement of chromosome is shattered which may also result in subsequent rejoining in haphazard order.

It is found that mostly cells do not survive due to these alterations and if they do, then may result in oncogenic fusion proteins or dysregulated expression of a particular gene that may bring more unwanted complications in individual cell.

'Code in Place', a computer coding course in Covid time

Learning during a grim phase of Covid Delta wave in India 

My log in page

When India was simmering with Delta wave of Covid-19, deaths were reported everywhere from one's neighbor to distant places, medical/social assisting system of every kind was disrupted completely, human dignity touched it's lowest point in our recent history; we sat in our homes with doors and windows closed and  mask on, isolating self in rooms possibly available, as if 'Covid-19 was in the air'. Hardly there was any home left where the family members were not with viral infective symptoms of some kind. People ran from one medical store to other in search of counter top medicine of some sort as there was no one to prescribe or guide to. This peak period ranged from mid April to the end of the May 2021. It was a period when 'Code in Place' came as rescue & refuge for many of us, here in India.

Shelter in Place vs Code in Place 2021 

OhYay for virtual Section

Phrase well suited to the situation when we all needed 'Shelter in place' and Stanford University provided us with 'Code in Place'. One can hardly imagine that how beneficial it was to us to engage us mentally for hours without any Covid-19 fear or isolation pressure from rest of our world. I sat transfixed to computer monitor, pouring attention to, unaware to the grim world outside, in my room at least for that much of the period. Thank you to all the distinguished team members of Stanford University for saving us from the rigorous pressure of the Covid Delta wave with unique opportunity of learning as well, a new skill set.

Coding in Places

Screenshot of a lecture video by Prof Mehran Sahami

It was a computer course in learning for coding and programming for Python language, based on Stanford University's CS106A, like the one they had in previous year in peak Covid-19 time of 2020. This was an online course, conducted for five weeks duration, requiring at least 10 hours per week, from April 19th to May 28th, 2021.

Karel commands from Karel Reader

For me it provided an unique experience of learning Coding in computer language Python. Each week with 3 days lecture videos, 1 day for 1 hour Section teaching, learning, problem solving activity with assigned  Section Leader of a Section around 10 students. Every week there were due assignments to solve and submit in due period. 'Karel' robot for initial learning of Python language, 'Ed' an online IDE hosting CIP community, 'OhYay' access for live Section for 1000+ section meetings around the clock across the globe engaging in virtual experiences were a huge shoutout. Hangout campfire by Section leaders was so useful to sort out and debugging of code written by any individual. Handouts, Lecture Videos, Lecture Slides, Files are still there for 'Life after Code in Place'.

While working on PyCharm IDE

Teaching by Mehran Sahami, Chris Piech, Julie Zelenski was a life time experience for the Coding. 

Meeka's design was selected by voting 

My experience was that the 'Content delivery' in teaching is a crucial part in communicating learning; while 'content', 'resource' and 'language-medium' matters little.

Final Project Showcase

  Learning Coding was like getting magical tool along with 12,000 students, 1125 Section Leaders from all across the globe in a Community Service gesture of Stanford University in the testing time of Covid-19.

Getting my final project published in the showcase of Code in Place 2021 was a real reward and a great opportunity of participation.

Thank you Mehran Sahami, Chris Piech, Julie Zelenski, Brahm Capoor and many more in the entire team of this project at Stanford University, expanding in all 7 continents and countries.

Map of Code in Place 2021, thankfully shared from 

Genetic code, Codon, Anti Codon, expression in Translation and Laws of heredity

--------------------------------------   

Basic molecular code of life:

--------------------------------------

Genes on Chromosome in the cell nucleus carry instructions for amino acids in the form of chemical alphabets. They are four nitrogenous bases: A, G, T, C; namely Adenine, Guanine, Thymine, Cytosine. U (Uacil) is found only in RNA, replacing T. 

These 4 nucleotides (A, G = Purines; T, C = Pyrimidines) of the DNA combine in various ways to form 3 letter code for any specific amino acid to the synthesis of protein.

Making of protein: Gene expression for the synthesis of protein is in two ways:

1. Transcription: Gene sequence of DNA strand is rewritten on mRNA with the help of transcriptase enzyme inside nucleus of the cell.

2. Translation: mRNA Nucleotide sequence is rewritten on tRNA with the help of polymerase enzyme, which in turn picks up a specific amino acid to form a polypeptide in Ribosome of the cell.

We encounter Codon and Anti Codon at the time of Translation.

Codon: A sequence of 3 nitrogenous Bases in a row on mRNA, as a message for the specific Amino acid.

Anti Codon: A sequence of 3 nitrogenous Bases in a row on tRNA on it's anti codon loop. They also have pseudo bases apart from the regular bases. These codon recognize the correct codon on mRNA by its complementary sequence.

Amino acid activation:

Amino acid + ATP --------> Amino acyl AMP +2Pi

Amino acyl + tRNA  --------> Amino acyl tRNA +AMP

                                               (tRNA loaded with Amino acid)

                                                   (cognate or charged tRNA)

Correct amino acid recognisation here by tRNA base (3' 5'), with complementary match with the base sequence on mRNA (5' 3').           

-----------------------                                       

Code crackers:

-----------------------
1. Physicist George Gamow in mid 1950s proposed the triplet hypothesis, this insight was mathematically suitable to code for essential 20 amino acids. 

This three nucleotide triplet code was the minimum to cover all the amino acids, later proved correct.

2. American biochemists Marshall W. Nirenberg, Robert W. Holley, Hargobind Khorana in 1960s did the pioneering work.

Nirenberg in 1961 with mRNA consisting poly-U, synthesized Phenylalanine (concluding UUU code for Phenylalanine) and later with poly-C mRNA translated to Proline (concluding CCC code for Proline).

Later Khorana experimented with poly-UC mRNA generated Serine and Leucine (concluding UCU code for Serine and CUC for Leucine).
In 1965 this code researcher  team deciphered the entire genetic code, including stop code, initiation code and received Nobel Prize in 1968. (above modified image from nobel.org, in public domain)

----------------------------------------------------------------------------

Gregor Johann Mendel (1822-1884), Father of Genetics

-----------------------------------------------------------------------------

Mendel (Czech) did his experiments on 10,000 pea plants for eight years (1856-1863), published his results in 1865. He concluded that genes come in pair and inherited as distinct units, one from each parent. He tracked the segregation of parental genes and their appearance as dominant or recessive traits in offspring.

He clearly recognized the mathematical pattern of inheritance from one generation to the next.

Mendel's Laws of Heredity are:
1, The Law of Segregation,

2. The Law of Independent Assortment,

3. Law of Dominance.

After his death, most of his personal papers and documents were burnt by the monks except few which remained in the archive of monastery.

Mendel on a postal stamp

      His laws were not understood until 1900 when independently three Botanist namely Hugo de Vries (Netherland), Correns (Germany) and Tschermak (Austria) rediscovered the findings of Mendel. 

      So Mendel put a blue print of things to come in the field of Genetics by deducing the laws of inheritance. 

       Meiosis, Chromosomes, Crossing Over, Genes, Linked Genes, Triplet Code were unknown in his time but his finding explains all this. His experimental results were rediscovered 16 years after his death and 34 years after he first published it. Triplet code came to be known only 100 years after his publication. Such was his genius as if he foresee all that. A friar, abbot who became 'Father', leaving no descendants behind, died at the age of 61 due to kidney ailment.

Reverse Transcriptase Polymerase Chain Reaction for Covid-19 and Zika testing

PCR 

Polymerase Chain Reaction is an in vitro diagnostic technique. This is being used to amplify the DNA or RNA sequence of any source material. 

In the PCR process a target DNA sequence and DNA Polymerase enzyme is used in lab conditions, usually passing with following cycles in stages:

1. Converting dsDNA to single stranded DNA,  

2. formation of new dsDNA  with one old strand and one new strand,

3. using new dsDNA as an template to for synthesis in next cycles.

RT-PCR 

Reverse Transcriptase Polymerase Chain Reaction is also an in vitro diagnostic technique with a variation of PCR. In this process a mRNA sample with reverse transcriptase enzyme, a cDNA copy is obtained. Here onward a standard PCR process is followed in sequence to obtain the dsDNA sequence. 

RT-PCR and Covid-19 

Often RT-PCR is combined with the real time PCR (qRT-PCR) to quantify the transcript levels in cells/tissues.

Originally radioactive isotopes were used in this nuclear derived method; now replaced by the isotopic labelling with special markers like fluorescent dyes.

Conventional RT-PCR allows to see the result at the end of the process while in qRT-PCR one can see result immediately while the process is still on going. This technique has been used successfully in diagnosing Ebola and Zika virus and is now adapted for testing the Covid-19 virus.

Further reference for:

Virus, genome and Covid-19

Mutation and Strain Biology of Covid-19 Virus

Spanish flue of 1918 

World is still fighting with the third wave of Covid-19 pandemic. Humans do have short memories as we forgot Spanish flu pandemic; a 100 year ago with fatalities in tens of millions at that time. Mutation in influenza, the RNA virus was behind the infamous pandemic. Understanding how virus mutates is critical for making decisions about the vaccines. RNA viruses mutate relatively quickly because they lack a proofreading mechanism to look for and repair errors during replication.

Actually there was no learning from that history, as our initial reaction with this new Covid-19 virus was of utter amazement. Still a lot lessons could be learned if we could visualize the after effects of the last pandemic of 1918.

Viruses fall on the borderline of living and non living.

They are strange as:

1. Do not have cell, a basic structural & functional unit of life to claim it as living organism,
2. Do not have their own metabolism of any kind, as do not possess any cell organelle,
3. Do not reproduce by any form of cell division,
4. Do self assembly only in a host cell, creating their multiple copies on the expense of host cell,
5. The only living characteristic they possess is gene, either in RNA or DNA strand form. They can not synthesize protein as they lack Ribosome, a cell organelle for the translation of viral mRNA,
6. The nucleic acid in RNA or DNA form alone is capable of infecting host cell even after being crystallized and stored for years in abiotic conditions. If and when that comes in contact with any host cell, starts behaving as a copy machine, producing of their own kind and consuming/killing the host cell.

Virus name in various Indo-European languages like Latin, Ancient Greek, Avestan means poison or poisonous substance, originating from Sanskrit root 'Visa'. 

Much before the discovery of structure of virus, it was identified as the poisonous substance rather than some biological entity.

Some specific features of viruses:

1. Viruses are submicroscopic in structure, shape ranges from helical to icosahedral to many more complex forms, invisible in the light microscope, as they are one-hundredth of the size of bacteria.
2. In nature their number is 10 times higher than the Bacteria.
3. Bacteriophage is a virus infecting to bacteria. 
4. Tobacco Mosaic Virus was the first virus discovered by Dmitri Ivanovsky in his 1892 experiments just at the end of the nineteenth century.

Wendell Stanley later studied the virus, managing to extract it in the form of pure crystals and show that it is composed of protein and ribonucleic acid (RNA) in 1935 and was awarded Nobel Prize in 1946.

Viruses consist of a long chain of either DNA or RNA, a protein coat Capsid surrounding and protecting the central genetic material and in some cases a lipid envelope surrounding the nuclear capsid.

Genomics of Viruses:

Of all the viruses found, about 70 percent are of RNA types genome. Due to possible higher rate of error in enzymes responsible for replication in RNAs type, they show much higher rate of mutation than to DNA viruses. That causes much higher rate of variant and that means the great adaptability to the new host.

The viral RNA may be of two types:
Single stranded (ss) or Double stranded (ds), they further vary as occupying on single RNA segment or two or more segments.

Genomes on single stranded RNA may further be of 2 types:

1. a sense strand (plus strand), which can function as mRNA; they alone can replicate if injected into host cell.

2. anti sense strand (minus strand), a complementary to sense strand, can not function as mRNA, no translational function, can not produce viral component.

The retrovirus genome comprises two identical plus-sense ssRNA molecules.
Most DNA viruses contain a single genome of linear dsDNA.

SARS-CoV-2, a corona virus causing Covid-19, is a RNA virus, and it must infect a host cell to replicate itself.
Error during the replication of viral RNA resulting in similar but not exact copies of the original, causing mutation. These mutant viruses called variants, which differ by single or many mutations.
A variant is called strain which shows distinct physical properties, behaving differently from the parent virus.

 
Following are the common variants of Covid-19 which are also strain; each containing several different mutation:

1. UK variant (B.1.1.7)

2. South African variant (B.1.351)

3. Brazilian variant (P.1)

Delta plus variant of Covid-19 is a warning that SARS-CoV-2 is continuing to evolve.

 

When new organisms enter the human race, they learn and adapt quickly to us. Unless we learn and adapt too, we're going to have more problems in the coming months and years. The virus is not done with us yet.

WHO says: 'When a virus is widely circulating in a population and causing many infections, the likelihood of the virus mutating increases. The more opportunities a virus has to spread - the more replicates and the more opportunities it has to undergo changes.'

Note: On the site of  WHO , this has been explained with a nice illustrative video to understand the mutational change in Covid-19 virus genome to form the newer variant. 

Following screenshots are shared thankfully from the above said video put in public domain to understand the possible change in four bases of the RNA's; i.e. Adenine, Guanine, Uracil, Cytosine. 

Delta wave of Covid-19

Delta, a variant of concern

India saw an unparallel devastation of human life, in the living memories of present generation, in the second wave of Covid-19 of Delta variant infection, which ran from mid April to mid May 2021. We are a nation of multitude of population. So in such a demanding situation, health infrastructure and system remained fail. We may have 'many' research institute, many oxygen plant, many hospital and serum institute in 'number', but when demand rose for providing it to 'per capita'; to our dismay, it proved a failure. And it was supposed to be. We are in no way capable of providing 'health needs' to such a 'large number' of people at any given instance, if a sudden pandemic rose even in future. Unfortunately disposal of dead bodies have also seen unprecedented scenario, which put humanity on shame.

People suffering, in desperate need of medicine, oxygen, hospital bed, doctor; and there was none. Disposal of dead bodies saw such painful and shameful visuals. Business of hoarding medical needs and market of fake medicine were on high. There is no 'actual number' of lives lost, because there was no one to record to in such a messy situation. Bonds of accountability of any kind was broken. A time of shame; pity, pain, tears ran high on faces of masses, those who lost their dear ones or children who lost their both parents; not to mention the neglect and negligence by the system to which we are proud of as most religious and democratic nation. Holy values saw a deepest dip of our time.

Delta plus variant acquired a spike protein mutation called K417N, the sub lineage of Delta, is on rise now. No one knows, what are in the store as mutation causes more transmissibility. Precaution measure and vaccines are the only answer at present.

First report from China was of 30th December 2019, later WHO issued disease outbreak news on 5th January 2020. Ever since, this virus has shown tendencies of a quick and efficiently evolving variants. Since one and half year, the cases and deaths are on rise, every minute. As of June 22, the country wise variant reported are; Alpha in 170, Beta in 119, Gamma in 71 and Delta in 85 countries. 

Lab leak theory of Covid-19

WIV image credit: Kyodo News via Getty

There is a huge debate these days about the origin of Covid-19/Corona/SARS-CoV-2; that this virus either has emerged from some zoonotic host in nature or it is bioengineered in some Virology lab. Before coming to any conclusion, it would be better to evaluate both possibilities in the light of available evidences. 

Possible spillover from nature: 

1. Most scientist believe that SARS-CoV-2 has a spillover from nature, because

bats are the known carrier for coronavirus. Horseshoe bat (Rhinolophus affinis) is commonly found in southern China. Genome of virus RATG13 found in this bat is 96 percent identical to the genome of SARS-CoV-2 causing Covid-19 in human.

2. This means that a closer link in between human and bat is missing for the difference of 4 percent genome.

3. Again the spillover from the lab is a remote possibility as lab engineered strain mostly cause small outbreaks. They are well documented and contained. 

4. Same covid-19 like pattern were found for emergence of infectious diseases causing pandemic in previous years; e.g. SARS coronavirus, influenza, Ebola, HIV etc. in other parts of the world.

5. 'WHO' too agreed for investigation in to pandemic's origin in depth (https://www.nature.com/articles/d41586-021-00375-7).

Lab leak theories are basically grounded on:

1. SARS-CoV-2's closest relative is still elusive to scientists.
2. Covid-19 first reported in Wuhan, is not a coincidence where WIV lab is researching on the same virus.
3. SARS-CoV-2 is spreading unusually quickly in humans, that points intention.
4. Furin cleavage site on virus protein spike, absent in it's closest relative. (But opponent to lab spillover theory believe it a convergent evolution for evolutionary advantage as virus adapting to the similar environment; as furin cleavage is also found on common cold viruses)
5. Original host of virus could not be found as yet.
6. CGG encoding for Amino Acid Arginine underlying a segment of furin cleavage site is preferred code for Arginine by humans, not viruses. (https://nicholaswade.medium.com/origin-of-covid-following-the-clues-6f03564c038). (But opposite believer point the 3 percent of Arginine been coded by CGG code in SARS-CoV-2, citing example of Indian variant (B.1.617.2 or Delta) has mutations in nucleotides encoding it's furin cleavage site, making it more virulent variant.)

Spillover theory and word of politics: 

There are many voices echoed in favor of a fair enquiry in this matter. 

1. US President Joe Biden tasked US Intelligence community to find the origin of SARS-Co-2. 

2. Australia, EU, Japan were also in the same league in voicing their concern for a fair investigation. 

3. World leaders in G7 summit were also vocal in a statement issued to the media on June 13, 2021.

(https://www.thehindu.com/news/international/g7-leaders-discuss-wuhan-lab-leak-theory-behind-covid-19-pandemic/article34804805.ece)

It's true that:
The Wuhan Institute of Virology (WIV) in China's central Hubei province is located in the same city from where the first Covid-19 were reported, but there is no substantial evidence to prove the controversial spillover theory from lab as of yet.

A spillover from nature through a bat directly or indirectly seems most likely.

Latest:
Amidst all the suspicion of lab leak theory, the Chinese Academy of Sciences reportedly nominated the 'Wuhan Institute of Virology' for top science award in conducting 'the most comprehensive and systematic identification research on the aetiology of covid-19'.
(https://www.wionews.com/world/wuhan-lab-suspected-of-leaking-covid-19-nominated-for-top-science-award-in-china-393263)

Corona virus outbreak, symptom, medicine, vaccine and lesson learnt

Corona Virus outbreak, causing severe acute respiratory syndrome (Covid-19) was declared a Public Health Emergency of International Concern on 30th January 2020 and a global Pandemic on 11th March 2020 by World Health Organization. Then it was thought as of zoonotic origin of some mammal like bat or other.

Covid-19 was first reported on 31st December 2019 from Wuhan, China. Spreading swiftly on global scale and adapting itself to gradually more lethal strain, surprised the medical community as well because mostly next level of strains are supposed to be less pathogenic, as considered generally.

Disease symptom is most intriguing so far as this affects different people in different ways. Common symptoms of fever, dry cough, tiredness, sore throat, diarrhea, loss of taste or smell to severe symptoms like breathing difficulty, chest pain, speech loss etc., ranging from 5-6 days to 14 days long period.

Getting blood oxygen level down is one point when body seems to be struggling for adequate supply of oxygen to their body parts. It is though lungs and RBCs who are the major player in this mechanism. Either lung being turned to morbid state or RBCs being in clotting phenomenon due to enzymes exudes of the virus, is yet to be fully explored and understood. But post-Covid death is all due to the organ failure at one or many level. Seriously infected patients even after been cured are suffering with many troubles of organ systems as one or more.

Medicines prescribed were mostly meant to take load away from fever and virus with immunity booster pills to fight; are the direction in which medicines were used by prescribing suitable doses of antipyretic, anti viral drugs and vitamin tablets. Plasma therapy in this case is used but with efficacy and validity controversy.

Vaccines in this turmoil came as the only hope, even infection after the second vaccine dose is also on the record. It was and still is a hard task economically and physically to administer to all human population. This pandemic period has shown us as we humans are sitting in the same boat. A person standing last in the line can not be left as he/she will be the asymptomatic carrier. Rich or poor, black or white are the world citizens as deserving equal rights of life, sustainability, health care and education. This is the time to learn this hard lesson for humanity. 

In India by the time of second Covid wave in March-April 2021, every kind of medical system was in total failure. People were asking for medical oxygen for anything and there was none. Death were so enormous that disposal of human dead bodies saw most unprecedented visuals of the century. India was truly devastated. Systems failed at many levels. 

Lessons learnt are to be carried with our life style now and that is cleaning hands often with soap and alcohol based rubs, maintaining safe distance, wearing mask, not going out when it's unnecessary, 

Delta variant is in the corner to meet us, we don't exactly know that what is in store of the Covid strain or some other viruses in future, safety should be the prime concern of every individual as for self and safety of other human fellows too.

Sun sneeze is a heritable trait

Sun sneezing, as name suggests is a photo sneeze reflex or better said a naso-ocular reflex caused by the exposure of an individual to bright light, so Photosneezia is another name came from. Claimed to be affecting 18 - 35 percent of world's population which is quite sizeable number as 1 in 4 persons are sun sneezers, whose exact physiology is yet to be explained.

It is well recorded in history by Aristotle and others but was less understood until recently.

Some believe that it may have evolutionary advantages for the cave dwellers in terms of spreading of pathogens present in their naso-pharynx, to their fellow cohabitants. It doesn't fits that way because we all should have had this in our DNA.

Rock Garden, Chandigarh, India

 

By 1980s it was established as a heritable autosomal dominant trait, is now called ACHOO syndrome (Autosomal-Dominant Compelling Helio-Opthalmic Outbursts), caused by single-nucleotide polymorphism on Chromosome 2, where a single base Adenine (purine) is replaced by Cytosine (pyrimidine) on DNA due to random mutation.

Being of dominant nature (name; the C allele on the rs10427255 SNP), it expresses itself even if being transmitted by the single parent through Chromosome 2 (location; 146,125,523). 

Physiology is simple as Opthalmic branch (Optic nerve) of Trigeminal nerve (longest Cranial nerve) inhances the irritability of the Maxillary branch to get sneeze.