Subject: Biotech and Medical Sciences

The PM has announced that the Indian SARS-CoV-2 Genomics Consortium (INSACOG) would be extended to India’s neighbouring countries.

What is INSACOG?

• INSACOG was established in December 2020 as a joint initiative of the Union Health Ministry of Health and Department of Biotechnology (DBT).
• It aims to expand the whole-genome sequencing of SARS-CoV-2, the coronavirus that causes the Covid-19 disease, across India with the aim of understanding how the virus spreads and evolves.
• It functions under the Ministry of Science and Technology with the Council for Scientific & Industrial Research (CSIR) and Indian Council of Medical Research (ICMR).

Composition of INSACOG

• INSACOG started out with the participation of 10 national research laboratories of the central government, and gradually expanded to a network of 38 labs.
• It now includes private labs operating on a hub-and-spoke model.
• These works to monitor genomic variations in SARS-CoV-2 by a sentinel sequencing effort which is facilitated by the National Centre for Disease Control (NCDC).
• It now involves the Central Surveillance Unit (CSU) under the central government’s Integrated Disease Surveillance Programme (IDSP).

Working of the INSACOG

• The data from the genome sequencing laboratories is analysed as per the field data trends to study the linkages, if any, between the genomic variants and epidemiological trends.
• INSACOG helps to understand super spreader events and outbreaks, and strengthen public health interventions across the country to help break chains of transmission.
• Linking this data with IDSP data and the patient’s symptoms helps to better understand viral infection dynamics, and trends of morbidity and mortality.
• The data can be linked with host genomics, immunology, clinical outcomes, and risk factors for a more comprehensive outlook.
• Sequencing assumes added significance as the incidence of reinfections and vaccine breakthroughs increases.

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The UK health authorities have confirmed a case of Monkeypox, which is a virus passed from infected animals such as rodents to humans, in someone with a recent travel history to Nigeria where they are believed to have caught it.

What is Monkeypox?

• The monkeypox virus is an orthopoxvirus, which is a genus of viruses that also includes the variola virus, which causes smallpox, and vaccinia virus, which was used in the smallpox vaccine.
• It causes symptoms similar to smallpox, although they are less severe.
• While vaccination eradicated smallpox worldwide in 1980, monkeypox continues to occur in a swathe of countries in Central and West Africa, and has on occasion showed up elsewhere.
• According to the WHO, two distinct clade are identified: the West African clade and the Congo Basin clade, also known as the Central African clade.

Its origin

• Monkeypox is a zoonosis, that is, a disease that is transmitted from infected animals to humans.
• Monkeypox virus infection has been detected in squirrels, Gambian poached rats, dormice, and some species of monkeys.
• According to the WHO, cases occur close to tropical rainforests inhabited by animals that carry the virus.

Symptoms and treatment

• Monkeypox begins with a fever, headache, muscle aches, back ache, and exhaustion.
• It also causes the lymph nodes to swell (lymphadenopathy), which smallpox does not.
• The WHO underlines that it is important to not confuse monkeypox with chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies.
• The incubation period (time from infection to symptoms) for monkeypox is usually 7-14 days but can range from 5-21 days.
• There is no safe, proven treatment for monkeypox yet.

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Almost everyone vaccinated for Covid-19 over the last 16 months will remember that he or she received a quick prick in the upper arm.

Why vaccines are generally administered into muscle?

• This is because most vaccines, including those for Covid-19, are most effective when administered through the intramuscular route into the upper arm muscle, known as the deltoid.
• There are several reasons, but the most important one is that the muscles have a rich blood supply network.
• This means whenever a vaccine carrying an antigen is injected into it, the muscle releases the antigen, which gets dispersed by the muscular vasculature, or the arrangement of blood vessels in the muscle.
• The antigen then gets picked up by a type of immune cells called dendritic cells, which function by showing antigens on their surface to other cells of the immune system.
• The dendritic cells carry the antigen through the lymphatic fluid to the lymph node.

Role of T Cells

• T Cells also called T lymphocyte, type of leukocyte (white blood cell) that is an essential part of the immune system.
• T cells are one of two primary types of lymphocytes—B cells being the second type—that determine the specificity of the immune response to antigens (foreign substances) in the body.
• Through the course of research over the years, it is understood that the lymph nodes have T cells and B cells — the body’s primary protector cells.
• Once this antigen gets flagged and is given to the T cells and B cells that is how we start developing an immune response against a particular virus.
• It could be any of the new viruses like SARS-CoV-2, the virus that causes Covid-19, or the previous viruses which we have been running vaccination programs for.

Other options for vaccination

• Conversely, if the vaccine is administered into the subcutaneous fat tissue [between the skin and the muscle], which has a poor blood supply, absorption of the antigen vaccine is poor and therefore one may have failed immune response.
• Similarly, the additives which could be toxic, could cause a local reaction.
• The same thing could happen when the vaccine is administered intradermally (just below the outermost skin layer, the epidermis).
• Hence, the route chosen now for most vaccines is intramuscular.
• Also, compared to the skin or subcutaneous tissue, the muscles have fewer pain receptors, and so an intramuscular injection does not hurt as much as a subcutaneous or an intradermal injection.

But why the upper arm muscle in particular?

• In some vaccines, such as that for rabies, the immunogenicity — the ability of any cell or tissue to provoke an immune response — increases when it is administered in the arm.
• If administered in subcutaneous fat tissues located at the thigh or hips, these vaccines show a lower immunogenicity and thus there is a chance of vaccine failure.

Why not administer the vaccine directly into the vein?

• This is to ensure the ‘depot effect’, or release of medication slowly over time to enable longer effectiveness.
• When given intravenously, the vaccine is quickly absorbed into the circulation.
• The intramuscular method takes some time to absorb the vaccine.
• Wherever a vaccination programme is carried out, it is carried out for the masses.
• To deposit the vaccine, the easiest route would be the oral route (like the polio vaccine).
• However, for other vaccines that need to be administered intravenously or intramuscularly (enabling wider field-based administration), the intramuscular route is chosen from a public health perspective over the intravenous route.

Which vaccines are administered through other routes?

• One of the oldest vaccines that for smallpox, was given by scarification of the skin.
• However, with time, doctors realised there are better ways to vaccinate beneficiaries.
• These included the intradermal route, the subcutaneous route, the intramuscular route, oral, and nasal routes.
• There are only two exceptions that continue to be administered through the intradermal route.
• These are the vaccines for BCG (Bacillus Calmette–Guérin) and for tuberculosis because these two vaccines continue to work empirically well when administered through the intradermal route.

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The World Health Organization (WHO) has flagged the emergence of a new variant of the SARS-CoV-2 virus — the XE recombinant.

How are variants created?

• SARS-CoV-2, the virus that causes COVID-19, is an RNA virus which evolves by accumulating genetic errors in its genome.
• These errors are produced when the virus infects a person and makes copies of itself inside the host’s cells.
• These errors (otherwise called mutations) are therefore a by-product of replication of SARS-CoV-2 inside the cell and may be carried forward as the virus continues to infect people.
• When viruses having a specific set of errors or mutations infect a number of people, this forms a cluster of infections descending from a common parental virus genome and is known as a lineage or a variant of the virus.

Who name these variants?

• The PANGO network, an open global consortium of researchers from across the world, provides a system for naming different lineages of SARS-CoV-2.
• Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature.
• These variants or lineages are widely followed by epidemiologists for tracking the evolution of SARS-CoV-2.

What is a recombinant variant?

• Apart from the errors in the virus genome, another process through which a virus increases its genetic diversity is recombination.
• Recombination occurs when, in extremely rare situations, two different lineages of the virus co-infect the same cell in the host and exchange fragments of their individual genomes.
• This generates a descendent variant having mutations that occurred in both the original lineages of the virus.
• Recombination of lineages happens in a variety of other viruses, including those that cause influenza, as well as other coronaviruses.
• Such recombination events occur typically in situations where two or more lineages of SARS-CoV-2 may be co-circulating in a certain region during the same time period.
• This co-circulation of lineages provides an opportunity for recombination to occur between these two lineages of SARS-CoV-2.

How many recombinant viruses have been detected?

• While recombination events are not frequently observed for the SARS-CoV-2 virus, multiple recombinant lineages have been designated during the pandemic.
• The recombinant lineages are annotated by PANGO with an ‘X’ followed by an alphabet which indicates the order of discovery.
• Some previously detected and designated lineages include XA, a recombinant of B.1.1.7 (Alpha) and B.1.177 detected in the U.K., lineage XB detected in the U.S., and lineage XC detected in Japan, which is a recombinant of B.1.1.7 (Alpha) and AY.29 sublineage of Delta.
• Three new recombinant lineages of SARS-CoV-2 have been recently designated by the PANGO network and are being monitored — XD, XE, and XF.
• Although currently present in a very low proportion of genomes in the U.K., early data from the country show evidence of community transmission of XF.

Are recombinant variants more deadly?

• Although recombination has been detected in SARS-CoV-2, it has not yet impacted public health in a unique way.
• There is little evidence to suggest that recombinant lineages have a varied clinical outcome compared to the currently dominant Omicron variant.
• It is certain at this point in time that more data will be needed to ascertain the impact of these lineages on the epidemiology of COVID-19.

What are the methods through which recombinants are identified?

• Identifying and tracking recombinant lineages for SARS-CoV-2 is a challenging task.
• This would require specialised tools and the availability of primary (or raw) data for genome sequences as similar variant combinations could also arise from inadvertent errors in sequencing or analysis as well as contamination of sequencing experiments.
• A cluster of recombinant genomes can be designated a lineage name by the PANGO network if it can be confirmed that samples in the cluster have a common origin and descend from two individual lineages of SARS-CoV-2.
• Additionally, there should be at least 5 genomes in the public domain belonging to the cluster, indicating an ongoing transmission of the lineage.
• Furthermore, screening the sequencing data of these samples should show no signs of contamination and meet the definition of a recombinant.

Way ahead

• Since recombinations are extremely rare occurrences, it is unclear how and why the viruses recombine.
• It is, therefore, important to track the recombination of SARS-CoV-2 lineages because it may lead to the generation of a viral lineage that is better at infecting people or transmitting from host to host.
• Monitoring circulating SARS-CoV-2 genomes for evidence of recombination will help gain a better understanding of the ongoing evolution of SARS-CoV-2.
• It will also provide information if a more “concerning” variant of the virus were to emerge.

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