Will herd immunity be effective against COVID-19 | 25th post - Antivirals | DESREM |Mylan | Vaccines | COVID-19 | US | Pfizer | Herd immunity | Remdesivir

Mylan received approval from DCGI for the generic version of Remdesivir, that can be used for treating COVID-19 patients in adults and children with severe illness of the disease. The drug will be available under the brand name DESREM at a price of 4800(INR) which is 70-80% lesser than the branded version.  Gilead sciences for the commercialization of Remdesivir in 127 low and middle-income countries(includes India). Remdesivir is 10^th medicine that has been collaborated with Gilead sciences and their first agreement was signed in the year 2006 for HIV treatment( tenofovir disoproxil fumarate).

Why antivirals are expensive?

Since antivirals are difficult to develop certain factors are to be considered, it includes Bioavailability, Lack of viable drug targets, Lack of the In-vitro model, Market size. Moreover, viruses require a host to live and most of the antibiotics can be used broad spectrum so it reduces the cost but when we consider for antivirals, each viral strain requires an antiviral.

Two COVID-19 vaccines showed prominent results in phase I trials, a DNA vaccine INO-4800 and an mRNA vaccine called BNT162b1. 34 people out of 36 trial participants completed the INO-4800 (94%). Trial participants demonstrated overall immune responses. Six weeks after receiving the two doses of INO-4800, participants were enrolled in 1mg or 2mg dose cohorts. Each participant received 2 doses of INO-4800 four weeks apart. The phase 1 study deals with safety and tolerability. Route of administration: intradermal injection.

40 healthy volunteers aged between18-50 were selected for the trial. 3 participants were excluded from the immune analyses because they tested positive for COVID-19 immune responses. INO-4800 is a nucleic acid-based vaccine that is stable at room temperature for more than a year(it means it doesn’t require to be frozen during transportation or storage), which is a very important factor for mass immunizations. INO-4800 targets the major surface antigen spike protein of SARS-Cov-2. The vaccine can generate balanced antibody and T-cell immune responses. This vaccine candidate is under PhaseII/III trial.

Another mRNA vaccine called BNT162b1 produced antibodies in healthy volunteers. This is a collaborative project between Pfizer and Biontech.  This study enrolled 45 participants who received two doses of the vaccine candidate. Blood levels of these antibodies were found to be more compared to people who recovered from the infection. 4 different mRNA vaccine candidates are been developed by Pfizer and Biontech against COVID-19.

Herd immunity VS COVID-19

Herd immunity is also known as social immunity, this occurs when a large population becomes  immune to a specific  diseases and transmission of disease from a person to a person becomes less. A certain percentage of the population is capable to get a disease and spread it, this is known as threshold proportion, if the proportion of the population that is immune to the disease is greater than a threshold, then the rate of a disease spreading will decline, this is known as herd immunity.

How this can be achieved?

There are generally two ways to achieve herd immunity- Vaccine and natural infection

1. Vaccines- This helps out by creating immunity against the disease without causing illness or complications. Herd immunity protects a certain population who can't be vaccinated like newborn babies or comprised immune systems. Some people may require revaccination as their immune system may be weaker against specific diseases.
2. Natural infection-When sufficient population who are recovered from the disease develop antibodies against infection. A good example to illustrate is 1918 influenza pandemic. Some people who survived this were later immune to swine flu (2009-10).

How to reduce the transmission of COVID-19?

Well, even though many of them may be aware of this, but still due to self-carelessness, the rate of infection may increase.

·        Avoid group gatherings

·        Avoid close contact with an infected or symptomatic person.

·        Maintain social distancing (within about 6 feet, or 2 meters)

·        Wear Face masks in order to reduce close contact in public places.

Many people may have a common question, whether if I follow those precautionary measures, will  I won't get infected. The answer may be no, it depends upon nature.

 

"By discovering nature, we discover ourselves"

Finally it is china- Sinopharm vaccine-first phase 3 trial | October 2020

Chinese vaccine - Sinopharm- Phase III trial

The Wuhan Institute of Biological Products, affiliated with Sinopharm becomes the first vaccine candidate to show beneficial safety and immunogenicity in phase I/II  clinical trials. China National Pharmaceutical Group Sinopharm (Sinopharm) is to begin a phase III trial in UAE and it is the first Chinese vaccine candidate that conducts the overseas clinical trial.

During the Phase I trial, 180 volunteers have been vaccinated and recently in phase II trial, 1000 employees of Sinopharm have been vaccinated and it showed safe and effective with adverse effects far lower than other vaccine candidates, a statement given by Sinopharm's officials. Sinopharm's Beijing Institute of Biological Products claims that they have the capacity to 20 million doses of the vaccine a year, while the company's institute in Wuhan will be capable of producing 100 million doses annually.

13 Experimental vaccines have entered human clinical trials and more than 120 others are in the earlier stage of development. 3 vaccine makers are set to race up as they are to enter later clinical trials. They are U.S-Moderna, China-Sinovac Biotech, UK’s Oxford-AstraZeneca. Among the vaccine candidates, china has six vaccine developmental projects that are undergoing human trials.

Top Candidate’s for COVID-19 Vaccine

1.         Oxford- AstraZeneca vaccine (PhaseII/III)

This collaborative  Vaccine project between  AstraZeneca and the University of Oxford, the AZD122 vaccine based on chimpanzee adenovirus called ChAdOx1 is to begin phase II/III testing in the UK and brazil. AstraZeneca has already begun for mass production of vaccines and plans to produce 2 billion doses by September.

2.         Moderna vaccine (phaseII)

This US-based firm is developing a messenger RNA based vaccine, its mRNA-1273 vaccine is set to begin testing on 30,000 people by July and this firm expects that the vaccine would be available by early 2021.

3.         Pfizer-BNTECH vaccine (PhaseII)

Pfizer has partnered with German firm BNTECH, 4 formats of mRNA based vaccine candidates are being tested in the U.S and Germany. Pfizer believes that their vaccine could be ready by the end of October 2020.

4.         Sinovac Biotech vaccine (Phase II)

This Chinese based firm is testing an inactivated vaccine called Coronavac and is preparing for phase III trials in China and Brazil. Based on Phase I/II data, it is safe and elicits an immune response in human trials.

What are the stages in the development of  a Vaccine

Preclinical stage: Invitro/Invivo studies

Invitro- A vaccine to be tested on cell lines.

InVivo- Vaccines will be tested on animals such as mice/monkeys and check for the immune response.

Phase I trial:  Experimental Vaccine will be given to humans and the subject ranges between 20-80 to test the safety and dosage of the vaccine. whether it stimulates the immune system.

Phase II trials- A large of people will be involved in testing and they will be differentiated into groups such as children and elderly people. This stage will be dealing with vaccine safety, immunogenicity, proposed doses, schedule of immunization, and delivery methodology.

Phase III trial- In this stage, the Vaccine will be given to 1000s of people for testing the safety and efficacy. After this, the concerned institution/organization will Submit application to the regulatory authority for approval.

Generic drugs | Remdesivir | CDCSO | DCGI | Medical masks | Cipremi | Covifor | Cipla | Hetero | Fabiflu | Glenmark

Medical Masks are Everlasting

Historians  believe that during the plague attack in Europe, Doctors started to wear masks that were made of leathers to prevent from bad air. These were preserved at Deutsches Historisches Museum in Berlin. Later on, microbiologists who were working on bacteria started to wear face masks in order to prevent microbes and dust particles.

It was in the year 1910, pneumonic plague strikes in Manchuria (a place in china), medical professionals adopted to wear face masks to prevent from this airborne disease. Later on, normal people and medical professionals adapted to wear face masks in order to prevent infection.

Types of masks and respirators

	Face mask ( Cloth or paper masks)	Surgical mask	N95 respirator	Surgical  N95 respirator
Purpose	Prevents  large particles expelled by the wearer from reaching the environment.	To be used as a physical barrier to protect from large droplets of blood or body fluids.	Reduces exposure to very small airborne particles or contaminants. May not protect against sprays and direct liquid splashes.	To be used as physical barriers from large droplets of blood or body fluids as well as small particles.
Filtration efficiency	Not applicable	Bacterial filtration efficiency above 95%	Minimum 95% against  particulate aerosols.	Minimum  95% against  particulate aerosols.
Fluid resistance	Absent	Yes	Not applicable	Yes

Generic version of Remdesivir

What are Generic Drugs?

Generic drugs are a type of medications that are copies of branded drugs which have the same dose, route of administration, quality, and performance.

Cipla and Hetero from India got approval to manufacture the generic version of Remdesivir for the treatment of COVID-19. Central Drug Control Standard Organisation (CDCSO) office of DCGI had granted permission to market Gilead science anti-viral drug Remdesivir in India for "restricted emergency use" on hospitalized COVID-19 patients.

Cipla launches generic version Remdesivir under the brand name ‘Cipremi’. The generic version will be available under the brand name ‘Covifor’(Hetero).  This ‘Covifor’ will be manufactured at hetero in Hyderabad.

Covifor (Remdesivir) will be available in 100mg vial (injectable) that will be administered intravenously under the supervision of healthcare practitioners. This drug will be available for use in hospitals. The supply will begin in a week. The price of the drug ranges between Rs.5000-6000 per 100mg vial. Cipla has not yet disclosed the pricing.

Based on a preliminary study conducted by Cipla,  results from ACTT-1(Adaptive COVID-19 Treatment  Trial) which had randomized clinical trials conducted with Remdesivir in 1063 patients, most of them were on oxygen support across U.S, Europe, and Asia. The mortality rate in the study was found to be 7.1% among given Remdesivir and 11.9% given through placebo.

Other pharma companies such as Zydus Cadila, Mylan, DRL and BDR pharma have submitted an application to DCGI to manufacture and market Remdesivir in India.

Many of us may be aware that Glenamark pharmaceuticals launched antiviral drug Favipiravir, under the brand name ‘FabiFlu’. This drug could be used for treating mild to moderate COVID-19 patients. This drug is available as a 200 mg tablet at a maximum retail price (MRP) of Rs 3,500 for a strip of 34 tablets. Each tablet costs Rs.103 and added that it is the first oral medication that is been approved in India for the treatment of COVID-19.

Story of Corona viruses | Pandemic | COVID-19 | Infection | MERS | SARS-Cov | Diseases

Story of Coronavirus

Everyone might be aware of COVID-19. But only a few may know the different strains of coronaviruses.  In the late 1930s, Coronaviruses were discovered in chicken that was infected by infectious bronchitis virus (IBV) but later in the 1960s only human Coronaviruses were discovered. The first strain was termed as B814 (number of the nasal washing) from a study conducted at Common Cold Unit of the British Medical Research Council by Kendall, Malcom Byone, and David Tyrrell. They found out that the virus could not be cultivated by a standard testing procedure. Eventually, Dorothy Hamre and John Procknow at The University of Chicago isolated a novel virus 229E, when both were inoculated, it caused cold in the volunteers, and the virus was inactivated by ether.

Common 4 human coronaviruses that have a mild infection

• 229E (alpha coronavirus)
• NL63 (alpha coronavirus)
• OC43 (beta coronavirus)
• HKU1 (beta coronavirus)

The other 3 types of coronavirus that causes severe infection:

1. MERS-CoV (Middle East Respiratory Syndrome, or MERS), is caused by the beta coronavirus group. The first case was reported in June 2012 in Saudi Arabia. The mode of infection is found to be from camels but some  scientists believe that it may be from bats. A larger outbreak occurred in South Korea (2015)  and in Saudi Arabia(2018). There is no specific vaccine or treatment for this disease.
   
2.  Severe acute respiratory syndrome coronavirus(SARS-CoV), is a type of coronavirus that infects bats. It also infects humans and certain mammals. It is a member of beta coronavirus. Two strains have been found for the outbreak during 2002-04. Bats are the main host for many of the strains of SARS-Cov. In 2016, WHO has found out that the future epidemic may occur after the ebola outbreak.
3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a  strain of SARS-Cov that causes COVID-19. The origin of this virus is believed to be from Wuhan, China. In January 2020, human to human transmission was confirmed. This disease has been declared a  pandemic by WHO.
   

541–542	Plague of Justinian
1346–1350	The Black Death
1899–1923	Sixth cholera pandemic
1918–1920	Spanish flu (H1N1)
1957–1958	Asian flu (H2N2)
1968–1969	Hong Kong flu
2009–2010	Swine flu (H1N1)
2019	COVID-19

2

 Fig: List of  Pandemic Diseases

                            

 

 When humans stop loving nature, Nature starts to love humans

Anakinra | Interferon-α2b | Oxford University | Moderna | Desert locust | Vaccine | COVID-19 | Nature | Short stories

Connecting With Other Beings

U.S-FDA approves fast track development of Moderna’s vaccine candidate, it approved for the phase-2 human trials and phase3 is to begin in the early summer. The phase 2  trial will consist of 600 candidates and if everything goes well, the vaccine production will begin as early as July.

An arthritis drug is found to cure severe COVID-19 patients,  an anti-inflammatory drug called anakinra is found to improve respiratory functions in severely affected COVID-19 patients.  This drug was treated with the patients who had secondary hemophagocytic lymphohistiocytosis that is characterized by over activation of the immune system and organ failure.

An antiviral drug named, Interferon(IFN)-α2b is found to improve the recovery rate in COVID-19 patients. Interferons are signaling proteins that are released when the virus infects the human body.  Interferons play a role in inhibiting the viral replication in every stage of the virus life cycle. The study was conducted by Dr. Eleanor Fish, an emerita scientist at the Toronto General Hospital Research Institute, University Health Network, and professor at the University of Toronto's Department of Immunology.

Oxford University vaccine candidate is found to be safe in Macaque monkey trials. During the study, the animals were found to be protective against pneumonia. The team is expecting to occur the same in the human trials too. 1000 volunteers have been registered for the human clinical trials.

DRDO lab in Hyderabad had developed a contactless sanitizer Defence Research Ultraviolet Sanitizer (DRUVS) for mobile phone and cash, laptops, and so on. This will be available in the upcoming week. 

Since many of them may know that swarm of the locust was seen in the states of Rajasthan and Madhya Pradesh a few days ago. A desert locust is a species of short-horned grasshoppers (Family: Acrididae). These locust species mostly feed on the crop vegetation which is considered as dangerous pests around the middle east, African, and southwestern  Asian countries. The major challenges of these pests are rapid growth production and the ability of swarms to fly across great distances. One such incident occurred during 2004-05 in western Africa, where major crop loss occurred and destroyed food security in that region.

How to control this?

It’s a big challenge to control locust attack but, there are certain ways in which insecticides can be used at a lower volume in order to prevent it. When there is a villain, there must be heroes to save the world.  Yes, they do exist, Predatory wasps and flies, parasitoid wasps, predatory beetle larvae, birds, and reptiles are natural enemies to desert locust, But they are effective is good against the smaller population. 

"Believe in nature, everything occurs for a reason" 

Vaccine INO-4800 | Social distancing | Vaccine for COVID-19 | BioNTech | Recombinant protein | Moderna’s mRNA 1273 | ChAdox1-ncov 19 | Coronavirus treatment | Clinical trial | USA | UK | China

Chinese biotech firm had proved positive results in an animal model and it is the first vaccine development that was tested in rhesus macaques. Sinovac  Biotech, a biotech firm in china gave 2 different doses of vaccine to 8 macaques and after 4 weeks of observation, none of them had the infection. The human trial began and during the animal testing, the best outcome came from the best dose. This company is a well-experienced vaccine maker and they have previously worked with diseases such as hepatitis A and B  and H5N1 influenza. The human clinical trial consist of 144 volunteers, to whom different doses of the vaccine were tested.

6 vaccines have entered the human trial and 77 more are under development. The major developer uses genetic engineering and the other 4 used old inactivation methods of developing.

Cansino's Ad5-nCov  completed Phase I trial

Cansino's Ad5-nCov  Vaccine candidate successfully completed the phase 1 human trial. This organization started enrolling volunteers for the phase 2 trial. It is a DNA based vaccine that used a recombinant protein approach for development. This firm has also already started working for the phase 2 trial of Ebola vaccine (Adenovirus) Ad5-EBOV. This company is planning to enroll 500 patients in Wuhan. 250 – phase I middle dose, 125-low dose, and 125 placebo injection. These are the number of people involved in dosage optimization.

 Johnson& Johnson

They have not yet started any human trail but they have been working with vaccine development with the same vector and signed a huge deal with HHS/BARDA. The phase I trial will not begin until September.  The adenovirus vector needs a correct approach to grow a more viral vector.

Insect cells  to develop recombinant proteins

The big giant Sanofi used their approach of developing vaccine by using insect cells to recombinant antigen proteins. This approach has been already approved for a flu vaccine. This approach is to be combined with GSK’s adjuvant (immune boosters).

 Vaccine INO-4800

Inovio-4800 is a DNA vaccine that is similar to that of the mRNA vaccine. This firm has been working on this for several years and other diseases such as MERS/SARS. They started with 40 volunteers in the US and another challenge is that they are developing a vaccine delivery devices for injecting through the skin.

mRNA based vaccine

BioNTech has a deal with Fudan's work on coronavirus vaccine in china. They have signed up a deal with Pfizer. German regulatory authorities have approved to begin Phase I and II trails. This trail is to enroll 200 volunteers for dosage evaluation.

ChAdox1-ncov 19

Oxford University has completed its phase I trial which had no safety problem and they are, to begin with, 510 volunteers for phase II trial. It is an Adenovirus vector from a chimpanzee that has a similar concept of the Cansino vaccine.

Moderna’s mRNA 1273

This US-based firm is expertise in mRNA therapies. They are in collaboration with NIH. The study will deal with 45 patients phase I trial in Seattle  and larger group at Emory which will have doses of 25,100,250 mg of mRNA in various age groups.

Summary:

• Inactivated virus vaccine- Wuhan institute for Biological products,  Sinovac’s PicoVacc
• mRNA based vaccine- BioNTech/Pfizer, Moderna mRNA-1273
• Adenovirus vaccine- Cansino's Ad5-nCov  , Johnson& Johnson,  Oxford Vaccine(ChAdOx1-nCov 19)
• DNA Vaccine- Inovio’s INO-4800
• Recombinant protein- Sanofi/GSK

ULTOMIRIS | SUPERCOMPUTER | US-FDA | COVID-19 KIT | DATA SCIENCE | GAMERS

Home Test for COVID-19

LabCorp, a diagnostic maker for COVID-19 will provide first access to health care workers to take the COVID-19 test personally, who are eligible to swab the fluid sample from the nose but they need to send the sample to the testing laboratory. The US-FDA has issued authorization for home testing of the COVID-19 kit. The person will need to swirl a cotton swab inside the nostril. Self swabbing will be more accurate according to the analysis done by the United Health group.

ULTOMIRIS to enter Phase 3 clinical trial

ULTOMIRIS is also known as Ravulizumab which is a type of monoclonal antibody that is used to treat paroxysmal nocturnal hemoglobinuria(PNH) in adults. PNH is a genetic disorder in which defective  RBCs break down at the premature stage and leaks in the blood.

Alexion Pharmaceuticals has announced to initiate a phase 3 trial of  Ravulizumab that comprises 270 adults with severe COVID-19 and severe pneumonia or acute respiratory distress syndrome. This phase is to evaluate the safety and efficacy of the drug and the primary goal is to survive on day 29. The secondary will be the need for ventilators, ICU, oxygenation.

The action of a plan:

Weight-based dosing  will be followed on day 1.

           

Dose (mg)	Weight (Kg)
2400	40-60
2700	60-100
3000	≥ 100

           

            

Days 5,10,15 will be also weight-based,  patients weighing 40-60kg will receive 600mg of  ULTOMIRIS, and patients with more than  60 kg will receive 900 mg of ULTOMIRIS. The treatment follows up will be for 4 weeks and followed by safety monitoring.

 Folding@Home

PC owners ad gamers have created the world’s fastest supercomputer to combat coronaviruses. Volunteers will have to run the app that uses their PC’s processing power to help the researchers for the finding of coronavirus vaccine. The name of the application is Folding@Home,  this uses resources from 1000 computers around the globe to work through large sets of numbers and complicated problems. This outperformed the 500 fastest supercomputers in the world combined. Researchers are using this supercomputing brain.

Mechanism of work: This app’s processing power will be used to understand how the spikes of coronavirus enter the human cell. Similarly, many studies are ongoing to detect how the spike of the SARS-COV2 virus attaches itself to human cells, infects the body, and takes hold of it. This app will develop future treatments through simulations of how spike proteins work. Single PC might succeed in developing a part of the process. Around 700,000 new users have joined Folding@ Home and around 30,000 people can run the app simultaneously.

It has reached 2.4 exaFLOps of processing power. Summit, it’s the world's fastest supercomputer, belongs to the US department of energy. Summit can reach a peak performance of 187 petaFLOps that is equal to under 19% of an exaFLOP. This app splits up complex protein models into tiny tasks that are distributed to many users around the globe. This app allows PC owners to decide what percentage of their computer’s processing power can be used.