Covid Variants
RAMA PRASAD T.
Dr. T. Rama Prasad,
Formerly: Medical Superintendent (Special) of RTS & IRT Perundurai Medical College and Research Centre,
Perundurai, Tamil Nadu. Presently: Director of ‘PAY WHAT YOU CAN’ Clinic, Perundurai, Erode District, TN – 638052.
Specially Contributed to “The Antiseptic” Vol. 118, No. 5
-------------------------------------------------------------------------------------------------------------------------------------------------------------------
Pyrrhic Victory: Winning the battle, losing the war.
“Grand strategy is the art of looking beyond the present battle.”
--. Robert Greene
Abstract
For some months after the ‘first wave’ of Covid, we seemed to have won the battle and been looking forward to win the Covid war with the ‘vaccine missiles’. Alas, things seem to be different in mid-April 2021. India’s daily case count on April 6, 2021 was the highest in the world. Despite beating down the first wave, panicky reactions to the ‘second wave’ have set in. ‘Dark-Covid-cloud’ looms large over India with the projection that the second wave could be more disastrous. Globally, coronavirus-related deaths crossed three million – two million in the first one year and one million in just three months later. International health officials blame the ‘Covid variants’ for the stomping surge. The variants seem to have spread fast and wide – the ‘Indian double mutant’ had reached San Francisco already ! The variants may ‘escape’ the protection supposed to be given by the vaccines that are currently being used. Restructuring strategies in the war against the virus, based on the behaviour of the variants, is called for. It's a humongous task to deal with, especially when the landscape of this pandemic is littered with knowns, unknowns and unknown unknowns. Some ‘known and unknown’ information about the Covid variants is documented in this article.
Key words: Covid variants, Viral mutations, Double Mutants, Vaccines for variants
Introduction
By nature, viruses mutate into various types leading to hundreds and thousands of variants or strains. However, only a few differ a lot to cause immense harm. The new coronavirus, SARS-CoV-2, is no exception. The words ‘Mutants’, ‘variants’ and ‘strains’ are often used interchangeably. Adverse circumstances force the viruses to change a little to adapt and thrive through mutations (changes during the process of duplication). And, the viruses carrying the mutations are called variants which may spread faster, be more lethal or render vaccines less effective. If this changed virus has distinctly different properties like increased transmissibility or virulence, it is called a ‘new strain’. A virus may differ by one or more mutations. There are three most common SARS-CoV-2 variants at present – the UK variant (B.1.1.7), the South African variant (B.1.351) and the Brazilian variant (P.1 / B.1.1.248). Crumbled countries are scrambling to contain the variants. Paradoxically, even America (where de la crème de status of healthcare prevails) went the way the cookie crumbled. Strategy to contain the variants is kaput.
History
SARS-CoV-2 is a new virus which started its journey in China (Wuhan) in December 2019, and spread fast and wide to 210 countries / territories across the world within a short period of less than five months. The coronavirus keeps on changing through mutations. The SARS-CoV-2 that is present in various countries now in 2021 may not be the same as the one that caused the first case in China and raced around the globe in 2020. Many varieties of the virus are in circulation across the world, apart from the emerging variants. The strains present in the US were similar to those in Europe, perhaps due to the travel factor.
The original Wuhan L strain was the first in India, which eventually mutated into the S and G strains and spread all over the country. Due to closing of the borders between States during the lockdown period in 2020, different types of mutations might have occurred in different States, according to the National Centre for Cell Sciences in Pune. There is a report that a Malaysia hotel owner returned to Malaysia from Sivaganga in Tamil Nadu, India on July 13, 2020 and infected 45 people in Malaysia out of which 3 had the D614G mutation. He breached his 14-day home quarantine, and was sentenced to five months in prison and a fine.
Nomenclature
Though the variants are usually referred to as 'strains' or 'mutants', they should more appropriately be called as 'lineages' or 'clades' or ‘subtypes'. Around ten lineages had evolved from the ‘ancestral’ Wuhan type. According to the ‘revised time-stamped nomenclature’, there were, as in August 2020, five lineages -- 19A, 19B, 20A, 20B and 20C. The lineages 20A, 20B and 20C have the D614G mutation. They go on mutating. Some die out as the mutations may not be advantageous to themselves. Some may become more virulent. While the G strain was the most common (which dominated the earlier D strain after March 2020), some have vanished. As in August 2020, a swap (transition) between amino acids, identified as D and G, at position 614 in the code of the virus's spike protein, produced a variant mutant called D614G which was the dominant strain worldwide. The D614G lineages also became dominant in India -- 20A in northern and Eastern; 20B in southern and western. The D614G mutant viruses are rapid spreaders, but not very lethal. They were very dominant in Europe and North America but not so much in East Asia.
The UK variant
Genomic sequencing of samples from patients with covid-19 in the south east of England in early October 2020 revealed the presence of a new lineage of the SARS-CoV-2, named ‘the UK variant’ (B.1.1.7 variant).1 In December 2020, ‘Public Health England’ identified this virus as a ‘variant of concern’ (VOC-202012/1). The first incidence of this new virus variant possessing 501.Y.V1 mutation was detected in the UK in September 2020, and within three months it had widely spread as a dominant variant in the UK and in many European countries, and later on it spread to 125 countries. It is present extensively in India and may be partially responsible for the second wave. In Canada, one care-home-worker got infected with the UK variant on January 8, 2021 followed within the next two weeks by 127 of the 129 care-home-residents reporting sick. And 32 of them died. That’s the speed of this variant which may become a dominant mutant (501.Y.V1) in 2021. And, it is 64% deadlier than the pre-existing strains (BMJ, March 10, 2021) and has 23 mutations in its genetic code – a relatively high number – and some of them made it more transmissible and deadly.2
The South African and Brazilian variants
The South African variant, known as 501.V2 / 501.Y.V.2 or B.1.351, was first detected in October 2020 in Nelson Mandela Bay in South Africa. It carries the mutations N501Y and E484K (known to evade antibodies produced by vaccines). In a very short period, it spread to more than 44 countries. More of younger people and women were affected. More cases of reinfection and more resistance to antibody therapies were noted.
The Brazilian variant, known as P1 variant (501.Y.V.3), was first identified in the Amazonian city of Manaus in Brazil in December 2020 and spread to over 20 countries. Cases surged exponentially (4,000 deaths a day) in Brazil, thanks to its “virus-sceptical far-right” president Bolsonaro.3 He said that Covid vaccines could turn people into crocodiles ! The P1 variant has been caused by three mutations -- E484K (also identified in the South African variant); N501Y (also present in the UK variant); and K417T. The variants made Brazil entangle itself in a terrible and horrific second wave.
Deadly trio
In the last three months of 2020, there had been the emergence and rapid rise in prevalence of the three independent “SARS-CoV-2 ‘501 Y’ lineages”: B.1.1.7, B.1.351 and P.1. It is reported in February 2021 that the UK variant mutated further into E484K and had been spreading fast like the South African strain B.1.135. On February 12, 2021, the UK variant which leaked from a quarantine hotel forced a snap lockdown in Melbourne in Australia making six million people to stay indoors for five days.
The two variants called ‘501.Y.V.2’ and ‘501.Y.V.3’ which have emerged in South Africa and Brazil, respectively, are fast-spreading and may dodge antibodies gained through previous infection or vaccination. Hence, people who developed immunity to the ‘regular’ virus may be susceptible to the variants. It is curious to know that as ‘herd immunity’ goes on increasing, the ‘regular’ virus runs out of the susceptible population and hence mutates into variants to have a vast susceptible population once again.
The Indian double mutant
For the first time in the world, the existence of a newly discovered “Double Mutation” variant was detected on December 7, 2020 and was announced by the National Centre for Disease Control (NCDC) on March 25, 2021, in India. B.1.617 is the name given to this variant. A ‘could-be-variant of concern (VOC)’, this variant has two important mutations -- E484Q (similar to the E484K mutation of the Brazilian, South African and the UK variants), and L452R (as the one found in California and Denmark). It is worrying because these mutations are linked to ‘antibody escape’ and increased infectivity. The significance of a third mutation called P614R is being studied. It may lead to the graduation of the ‘double mutant’ into ‘treble mutant’ through its sartorial excellence of wearing a third coat ! The B.1.617 is currently linked to 15% to 20% of the cases in Maharashtra, in India.4 At ‘jet-speed’, it entered America. That’s the ‘viral speed’! The Clinical Virology Lab at Stanford Health Care had confirmed one case of the India’s new ‘double mutation’ COVID variant in April, 2021. And, seven suspected cases are under investigation at Stanford Hospital’s various clinics around the San Francisco Bay Area. Eight other countries reported the presence of this variant.
Dangerous variants in India
The Indian SARS-CoV-2 Consortium on Genomics (INSACOG), which is a grouping of 10 national laboratories established by the Ministry of Health, analysed 10,787 samples through genomic sequencing and found 771 ‘variants of concern’ as on March 24, 2021. At least, 34 cases of the South African variant (present in 44 countries) and one case of Brazil variant (present in 20 countries) have been detected in India, in addition to the 736 of the UK variant (present in 125 countries). As the genome screening increases, the numbers would go up. The mutations E484Q / E484K (similar to the South African and Brazilian variants) and N440K (the first detected in Andhra Pradesh) were found in Maharashtra in the first quarter of 2021. These are more transmissible and may cause more pneumonia deaths. A very recent addition is the ‘Double Mutation’ variant of India. Maharashtra, Madhya Pradesh, Punjab, J&K, Gujarat and Haryana began to show early signs of an ominous and furious ‘second wave’ in 2021. India can’t afford another ‘lockdown’.
Super-variants
Added to the confusion is the potential emergence of “Convergent Mutants” through “convergence” (naturally combining qualities) of the variants. This is the evolutionary capacity of the SARS-CoV-2 to adapt to changing ‘herd immunity’ and the public health interventions such as vaccinations and other preventive measures. Adaptation is the key point as mentioned by Charles Darwin long ago. For example, the three independent SARS-CoV-2 “501Y lineages” -- B.1.1.7, B1.351 and P1 -- which were under intense stress of natural selection, independently acquired multiple, unique and convergent mutations. This may be the cause for the emergence and rapid rise in prevalence of COVID-19 during the last three months of 2020 in the western countries.5
Impact on vaccination
Great worry is looming large about the impact of variants on the efficacy of the currently available Covid vaccines. As most of the vaccines target different regions of the coronavirus spike protein, they won’t all be equally affected by the same mutation. It is found that D614G is impacted by antibodies developed by COVID-19 disease or vaccination. The D614G mutation alters the spike protein, but not the critical ‘receptor binding domain (RBD)’ of the immunogenic part at the tip of the spike which binds to the ACE2 receptors on human cells. Cross-protection by the currently available vaccines may be expected against the variants to some extent, especially protection against serious forms of COVID-19 or death. But we are not sure at present, as some variants are known to “escape” (evade neutralising antibodies). It is reported that ‘Johnson & Johnson vaccine’, said to be effective against the 501Y.V2 mutation, would be used instead of the AstraZeneca vaccine in South Africa. Perhaps, Novavax vaccine may also play a similar role. In general, protection may be good against D614G, the ‘original variant’. But newer ones like Y453F and L452R can escape from the restricted cellular immunity.
If need be, ‘new’ vaccines can easily be made now by the technique called ‘tweaking’ (adjustment). Within six weeks, it can be made in the case of mRNA vaccines like ‘Pfizer’ and ‘Moderna’. For others, it may take up to six months. The complex possibilities and implications are being studied.
Sad situation
The virus is still thriving well in different ‘dresses’ of variants (it was one year ago, on March 11, 2020, that the WHO declared it as a pandemic). During this one year, globally, the numbers had surged nearly 1,000 fold – 0.118 to 118 million cases, and 4,291 to 2.6 million deaths ! A very sad commentary, indeed. In India, the surge is much more than 1,000 fold – 500 to 13.2 million cases, and 10 to 1,68,436 deaths. The ‘medical world’ shrugged its metaphoric shoulders ! Despite India’s pre-emptive and proactive approach, there seems to be a galloping surge of a “second wave.” The spectre unfolding across India is stark and scary – 100 cases every minute and a death every two minutes, in mid-April 2021. Maharashtra and some other States declared ‘night curfews’ and ‘partial lockdowns’. ‘Double mutation’ variants – E484Q and L452R -- have emerged in Maharashtra. India is gripped by the fast and furious ‘second wave’ which is predicted by the ‘super mathematical modelling’ to ‘peak’ in the third week of April 2021. But, predictions may go wrong, and nothing seems to be certain with ‘Corona’. It would be disastrous if ‘variants’ are the main cause for the tragedy.
Variants conundrum
One year on, sensational news like “highest spike”, “alarming deaths”, “Astra blood clots”, “doctors tested RT-PCR positive even after being vaccinated”, “another vicious variant”, etc. has been hitting the headlines, though we feel ourselves increasingly numb to the shock factor that the headlines are supposed to trigger. Brazil had more than 4,000 deaths in 24 hours (April 7, 2021), as a more contagious variant fuels a surge in the cases. “If Brazil is not under control, then the planet is not going to be safe, because we are brewing new variants every week … and then are going to cross borders,” said Dr. Miguel Nicolelis, who has been closely tracking cases in Brazil. Many experts feel that the variants are playing an important role in the current speedy surge in the cases in India.6 However, based on the findings of the Centre for Cellular and Molecular Biology of the CSIR, Indian authorities didn’t find much evidence to incriminate the variants in the bourgeoning second wave in India. But, official figures, sometimes, hide more than they reveal. Let’s hope for a fortunate stroke of serendipity.
REFERENCES
2. https://www.bmj.com/content/372/bmj.n579
3. https://www.bbc.com/news/world-latin-america-56657818
5. https://www.medrxiv.org/content/10.1101/2021.02.23.21252268v1
I started on COPD Herbal treatment from Ultimate Health Home, the treatment worked incredibly for my lungs condition. I used the herbal treatment for almost 4 months, it reversed my COPD. My severe shortness of breath, dry cough, chest tightness gradually disappeared. Reach Ultimate Health Home via their email at ultimatehealthhome@gmail.com . I can breath much better and It feels comfortable!
ReplyDelete