Proposed Vaccines, Treatments in the Context of COVID-19

Coronavirus disease 2019 (COVID-19)

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Vaccines

Vaccines prevent or mitigate infections.
They are designed to induce a protective immune response in the body against the viruses.
When vaccinated, the immune system of the body produces a specific response, consisting of specific T cells & specific antibodies that fight off the infection when exposed to the virus occurs at a later stage.
More importantly, vaccination also leads to the induction of a specific immunological memory against the viruses represented in the vaccine.
There are about a half-dozen basic types of vaccines, including killed viruses, weakened viruses, & parts of viruses, or viral proteins.
All aim to expose the body to components of the virus so specialized blood cells can make antibodies.
In the past, it has been difficult to manufacture vaccines for new zoonotic diseases quickly.
A lot of trial & error is involved in making a vaccine. Hence it could take years to invent a vaccine.
A new approach being taken by Moderna Pharmaceuticals, which recently began clinical trials of a vaccine, is to copy genetic material from a virus & add it to artificial nanoparticles.
This makes it possible to create a vaccine based purely on the genetic sequence rather than the virus itself.

Differences between Vaccine & Drugs

Vaccines	Drugs
Vaccines are almost always biological products – Subject to widespread variation even between batches.	Drugs may be chemical or biological Chemical drugs have remarkable identity between batches & even between manufacturers.
All vaccines require special conditions of storage – usually cold storage.	Chemical drugs do not usually require cold storage. Some biological drugs may require cold storage e.g. Insulin. Most chemical drugs are administered orally as tablets, capsules, suspensions etc.
Vaccines are large molecules usually administered parenterally. Some vaccines may be given orally (e.g. polio vaccines) or intranasally.	Some drugs are given through various other routes e.g. IV, IM., SC, dermally etc.
Vaccines are normally given in “schedules” which must be adhered to– For whole populations and/or age groups.	Use of drugs is individualised.
Vaccines are given mostly to PREVENT disease.	Drugs are given to treat, diagnose or prevent disease.
Vaccines are supposed to protect whole populations (“herd immunity”)	Drugs are normally for the benefit of the individual.
Examples- Covaxin, ChAdOx1, SputnikV.	Examples- Itolizumab, Hydroxychloroquine, Dexamethasone, Remdesivir

Antiviral treatments for COVID-19

Antivirals

Antivirals are drugs that can treat people who have already been infected by a virus.
They also can be used to prevent or limit infection when given before or shortly after exposure, before illness occurs.
A key difference is that the antiviral drug is effective only when administered within a certain time frame before or after exposure & is effective during the time that the drug is being administered.

Antibiotics

Antibiotics are medicines that interfere with the reproduction of bacteria & are, therefore, only useful for treating bacterial infections.
Viral diseases, like influenza, can therefore not be treated with antibiotics.
Inappropriate use of antibiotics contributing to the development of antibiotic resistance.
Secondary bacterial infections that may occur in tissues that have been damaged by influenza virus infection may well be treated with antibiotics.

Antiviral treatments use various tactics to slow down the virus’s spread, though it is not yet clear how effective any of these are.
Chloroquine & hydroxychloroquine, typically used to fight malaria, might inhibit the release of the viral RNA into host cells.
Favipiravir, a drug from Japan, could keep viruses from replicating their genomes.
Combination therapy of lopinavir & ritonavir, a common HIV treatment that has been successful against MERS, prevents cells from creating viral proteins.
Some believe the ACE2 protein that the coronavirus latches onto could be targeted using hypertension drugs.
Another promising approach is to take blood serum from people who have recovered from the virus & use it & the antibodies it contains as a drug.
It could be useful either to confer a sort of temporary immunity to health-care workers or to combat the virus’s spread in infected people.
This approach has worked against other viral diseases in the past, but it remains unclear how effective it is against SARS-CoV-2.

Major Vaccines in News in the context of COVID-19

What is ZyCoV–D?

ZyCoV-D is a plasmid DNA vaccine, under the Vaccine Discovery Programme supported by the Department of Biotechnology under the National Biopharma Mission.
Plasmids are circular deoxyribonucleic acid (DNA) vectors that can be used as vaccines to prevent various types of diseases.
In the pre-clinical phase, the vaccine was found to elicit a strong immune response in multiple animal species like mice, rats, guinea pigs & rabbits.

What is Oxford’s ChAdOx1 Covid–19 vaccine?

Vaccine, based on a chimpanzee adenovirus called ChAdOx1, elicited antibody & T-cell immune responses.
Oxford’s AZD1222 vaccine is made from a genetically engineered virus that causes the common cold in chimpanzees.

What is COVAXIN?

It has been developed by the company Bharat Biotech India (BBIL) in collaboration with ICMR’s National Institute of Virology (NIV).
It is an “inactivated” vaccine — one made by using particles of the Covid–19 virus that were killed, making them unable to infect or replicate, ie non replicating.
Injecting particular doses of these particles serves to build immunity by helping the body create antibodies against the deadly virus.

What is Non–Replicating Viral Vector?

The SARS–CoV–2 virus uses the spike on its surface, the ‘spike protein’, to enter & infect cells & multiply.
A non–replicating viral vector vaccine uses a weakened version of a different virus to carry this Covid–19 spike protein into the body, but it is modified not to replicate.

What is the mRNA vaccine?

RNA Vaccine	DNA Vaccine
These use messenger RNA (mRNA) molecules that tell cells what protein to build. In this case, the mRNA is coded to tell cells to build the molecular structure on the surface of SARS–Cov–2 — which the immune system will recognise & build antibodies against.	These vaccines use genetically engineered DNA molecules that, again, are coded with the antigen against which the immune response is to be built.

The genetic blueprint (or code) in living organisms is stored in a double-stranded molecule called DNA (deoxyribonucleic acid), which makes proteins that are responsible for nearly every function in the human body.
The conversion of DNA code into proteins requires a single-stranded molecule called the mRNA (messenger ribonucleic acid).
In an analogy with computers, one may think of the DNA as the hardware, the mRNA as the software & proteins as the applications.
The mRNA-1273 is a piece of RNA that carries the code to make the COVID-19 virus Spike protein when introduced into cells.
This protein present on the virus surface is critical for its entry into cells. Immunity (antibodies) to the Spike protein can block virus entry & its multiplication, & thus ameliorate the disease.

Sputnik-V

This vaccine has been developed by Moscow’s Gamaleya Institute in collaboration with Russia’s defence ministry.
The vaccine is based on the DNA of a SARS-CoV-2 type adenovirus, a common cold virus.
In this vaccine, adenovirus is used as a tool to deliver genes or vaccine antigens to the target host tissue.
The vaccine uses the weakened virus to deliver small parts of a pathogen & stimulate an immune response.
The vaccine is administered in two doses & consists of two types of human adenovirus, each carrying an S-antigen of the new coronavirus, which enter human cells & produce an immune response.

Which is the Best Vaccine Suited for India?

Comparing the top three vaccines based on:

Efficacy Rates

Pricing

Pfizer’s candidate is the steepest one right now, costing $20 per dose.
Moderna’s make comes up to cost somewhere around $15-$17 per dose.
Oxford-Astrazeneca’ shot is by far the cheapest vaccine under offering, as little as $5- $6 (Rs.1000).

Side Effects

Both Moderna & Pfizer-BionTech haven’t reported the occurrence of undue or alarming side-effects.
Neither have reports of adverse reactions emerged from people who have been vaccinated right now.
In comparison to this, the Oxford-Astrazeneca vaccine has been surrounded by controversies in the past months with the many ‘strange’ side-effects being reported from volunteers

Storage & shelf-life

Storage & shelf-life are prime factors that determine how effective a vaccine would be in real-world settings.
Many experts claimed that Pfizer’s vaccine model will not be well-suited for developing nations, since it requires extreme temperature settings to be stored in & additional shipping ingredients.
The vaccine can be stored for use for up to 5 days’ time in a regular refrigerator, for 30 days in a dry-ice freezer, or 6 months’ time in ultra-cold freezers, which are not feasible to arrange everywhere.
Moderna faces similar challenges but is slightly less expensive to ship & can stay stable for a longer time, as compared to Pfizer.
Oxford’s dose, wins since it is a vaccine prepared using traditional settings, can be stored for use for longer months, easily delivered & administered.

Important Drugs in News in the context of COVID-19

What is Itolizumab?

This was used for treating chronic plaque psoriasis.
Plaque psoriasis is a chronic autoimmune condition in which skin cells build up & form scales & itchy, dry patches.
It can also be used in the treatment of CRS in moderate to ARDS in severely affected patients of the corona.
CRS (cytokine release syndrome) & ARDS (acute respiratory distress syndrome) happen due to COVID–19 suffering.
CSS is an uncontrolled attempt by the immune system to neutralise the virus that often ends up damaging the lungs & other organs & even death.
ARDS is a disease in which the lung loses its capacity to expand further.
Biocon’s biomanufacturing facility which is located at Biocon Park in Bengaluru will be manufacturing & formulating Itolizumab as an intravenous injection.
Biocon has licensed Itolizumab from Cuba twenty years ago & this is an original innovative Indian drug.

What is Hydroxychloroquine?

It is a drug used in the treatment of autoimmune diseases such as rheumatoid arthritis & lupus.
Hydroxychloroquine (HCQ) is also used for the prevention of malaria & its treatment; it is a derivative of the antimalarial drug chloroquine.
Hydroxychloroquine can only be used in places where chloroquine is still effective.
There are only a few places left in the world where hydroxychloroquine is still effective including parts of Central America & the Caribbean.

Hydroxychloroquine: Why is it so much in the spotlight?

The prime mover of the theory that HCQ works against Covid–19 has been President Trump, starting with his tweet in March: “HYDROXYCHLOROQUINE & AZITHROMYCIN (antibiotic), taken together, have a real chance to be one of the biggest game-changers in the history of medicine.

What is Dexamethasone?

Dexamethasone reduces the production of the chemicals that cause inflammation & also reduces the activity of the immune system by affecting the way white blood cells function.
Dexamethasone falls in a category called corticosteroids, which closely mimic cortisol, the hormone naturally produced by the adrenal glands in humans.
It is commonly used in treatment for rheumatological inflammatory conditions: inflammations of muscles, inflammation of blood vessels, chronic arthritis, & lupus.
It is used in lung diseases, kidney inflammation & eye inflammation, & to reduce swelling associated with tumours of the brain & spine.
In cancer patients, it is used to treat nausea & vomiting caused by chemotherapy drugs.

How Useful is it in Covid–19 Treatment?

During the SARS outbreak in 2003, corticosteroid therapy was used to reduce inflammatory–induced lung injury.
In Covid–19, too, many countries are investigating the effectiveness of corticosteroid therapy on patients with an acute respiratory infection.
Also, the World Health Organization (WHO) has prioritised the evaluation of corticosteroids in clinical trials to assess safety & efficacy.

What is Remdesivir?

Its an antiviral drug being used to treat COVID–19 patients.
Remdesivir is designed to obstruct the stage of replication, when the virus creates copies of itself, followed endlessly by the copies creating copies of themselves.
Polymerase enzyme is targeted by remdesivir

How does replication take place?

Once the virus enters the human cell, it releases its genetic material, which is then copied using the body’s existing mechanism.
At the replication stage, the key viral protein at play is an enzyme called RdRp (an enzyme is a kind of protein that speeds up chemical reactions within a cell).
It is RdRp that makes the copies, by processing components of the RNA of the virus.
In scientific literature, such an enzyme is called a polymerase (the p is RdRp stands for polymerase) or a replica. In any case, this is the enzyme that is targeted by remdesivir.

How exactly does remdesivir target this enzyme?

In order to replicate, the copy machine processes raw material from the virus RNA, broken down by another enzyme with that specific function.
When a patient is given remdesivir — the inhibitor — it mimics some of this material, & gets incorporated in the replication site.
With remdesivir replacing the material it needs, the virus fails to replicate further.

How far has this action been established?

The drug itself was designed to act against the Ebola virus, which is not a coronavirus.

Favipiravir

Favipiravir is an antiviral given to inhibit viral replication.
It is used as an anti-influenza drug.
It is being used for moderately symptomatic to severely ill Covid patients, but access is not easy.

Plasma Therapy

What is Plasma?

Plasma is the almost–clear liquid left behind after RBCs; WBCs & platelets are removed from the blood.
Plasma fluid carries the blood components throughout the body.

Link– Source & Credits
Plasma is the largest part of your blood. It makes up more than half (about 55%) of its overall content.
When separated from the rest of the blood, plasma is a light–yellow liquid.
Plasma carries water, salts & enzymes.
The main role of plasma is to take nutrients, hormones, & proteins to the parts of the body that need it.
Cells also put their waste products into the plasma.
The plasma then helps remove this waste from the body.

What is Convalescent Plasma Therapy?

Convalescent plasma therapy is an experimental treatment that some doctors are using for people with severe coronavirus disease in 2019 (COVID–19).
People who’ve recovered from COVID–19 have antibodies — proteins the body uses to fight off infections — to the disease in their blood.
The blood from people who’ve recovered is called convalescent plasma.
Researchers hope that convalescent plasma can be given to people with severe COVID–19 to boost their ability to fight the virus.
It also might help keep people who are moderately ill from becoming more ill & experiencing COVID–19 complications.

Link– Source & Credits

Plasma vs Serum

Serum is plasma minus the clotting factors & blood cells.
While removing the clotting factors (by centrifugation), the protein fibrinogen is converted to fibrin.
Fibrin is an insoluble protein that is used to assist in the repair of tissue damage by forming a clot.
A key difference between plasma & serum is that plasma is liquid, & serum is fluid.
Plasma contains fibrinogen which is absent in serum.
Both plasma & serum can be extracted from blood but it’s worth noting that serum is obtained after the clotting of blood, while plasma can be obtained before the coagulation of the blood.
Serum is mostly used for blood typing but is also used for diagnostic testing.
Plasma, on the other hand, is mostly used for blood-clotting related problems.