SARS-CoV-2 mutations and implications

The police stop commuters at a checkpoint as the government enforced a strict restrictions to combat the spread of the COVID-19 in Dhaka on April 14. — Agence France-Presse/Munir uz Zaman

MUTATION in pathogens — germs which cause illness in humans, animals, birds or plants — is a natural process like evolution in animals and birds. Like evolution, mutation imparts pathogens evolutionary advantage to survive against threats to their existence. Among viruses, which can live only in live cells of a host, mutation is frequent. When a virus multiplies or rather replicates in a host cell, its replicated forms are edited to ensure that these are similar to the original virus. The editing function is, however, weak in an RNA virus and, hence, mutation is more frequent in them. The longer the viral genome is, the more would be the chance of difference between the original and the replicated virus, ending in mutation.

Human coronaviruses and cross immunity

OF THE 30 coronavirus strains, some of which had been in existence for millions of years, so far seven have been found to infect humans. One, the SARS (severe acute respiratory syndrome) or SARS-1 of these seven strains, remained untraced since 2004. Four strains — HKU1, OC43, NL63 and 229E — have been incriminated to cause 30 per cent of the common cold in the winter season globally and, perhaps, also in Bangladesh. This is said to be a strong reason as to why the poor living in urban slums in squalid conditions, with greater possibility of exposure to these four cold-causing coronaviruses, do not come down with severe form of COVID-19, when infected with the SARS-CoV-2 strain. The possible immunological explanation is that because of frequent exposure, in the light of more exposure potential to the four human coronaviruses, people in slums may develop some degree of immunity to other forms of human coronaviruses, however weak it might be, including that against COVID-19.

This virological phenomenon is called homologous immunity — immunity to phylogenetically similar viruses. Another phenomenon is known as viral interference. If a virus gains entry into a host, a closely similar/homologous strain of the same virus family is barred by the virus which already got a foothold in the same host. This viral interference phenomenon might yet be another cause as to why those who are thought to be infected frequently with a virus are not infected easily or seriously by another homologous virus. This may happen also when a mutated virus infects a person, infected earlier with an earlier version of the same strain or when vaccinated against a previously existent mutant.

Current SARS-CoV-2 mutations and implications

THE Indian variant (B.1.617), like that of the recent South African (B.1.351) and Brazilian (P.1 variant which originated from B.1.1.28 lineage) variants, also has a mutation at 484 codon position. A codon is a complex of three nucleotides/nucleosides — the building blocks of an amino acid — which in turn is the building block of proteins. This mutation, for example, changes the code for amino acid glutamate (E) to that for lysine (K) in the South African and Brazilian variants and glutamine (Q) in the Indian variant. The South African, Brazilian and the UK variants (B.1.1.7) also carry a mutation, called N501Y — amino acid asparagine changing to tyrosine. The Indian variant has another mutation at codon position 452, changing to L452R (amino acid leucine changing to arginine). The E484K/Q mutation helps the virus to evade a host’s immune system and it, thus, may pave the way for reinfection and make an infected person’s life precarious.

The N501Y and the L452R mutations make the viruses stickier to hold tight to the host cell, replicate faster and, thus, make it more transmissible and overburden hospitals. Mutations can result in 20 per cent more deaths among the patients sent to hospital, as observed in South Africa. Because of the fast growth and higher rate of transmission, these variants also infect younger people and children relatively easily, even though these young ones possess a fewer docking sites for the virus (ACE-2) in their body system. The South African variant also contains another important mutation — K417N. Earlier studies indicate that the K417N mutation occurs within the area considered the main target of host’s neutralising antibodies which is, therefore, thought to empower the virus to escape the host’s immune system.

A new variant has been detected recently in Manhattan of New York and in areas close by. Two mutations in two isolates were found in Manhattan but named so far the same — B.1.526. One is similar to the variant first seen in South Africa that allows the virus to dodge vaccines to some extent and the host’s immune system because of the E484K mutation. The other mutation,  S477N, may help the virus like the L452R and N501Y mutations to tightly bind the virus to human cells. The Manhattan variant can also replicate fast. The variant was first seen in the city in November. By the middle of February, it accounted for roughly one in four infections, according to the New York Times. The patients carrying the mutation were found to be about six years older on average with more likelihood of ending up in hospital.

Recent research suggests that B.1.526 should be closely watched for its ability to escape both monoclonal antibody and, to some extent, the vaccine-induced antibody. It is guessed that the variant may have arisen in November in immune-compromised people who were sick despite treatment over a long period of time. The same is assumed for the advent of the UK variant.

Scientists in California found a more transmissible (24 perc ent higher transmissibility) variant, which they think may be more resistant to current vaccines. The variant, B.1.427/B.1.429, was not seen in September 2020, but by January 2021, it had become the predominant variant in California, with cases doubling every 18 days, as the New York Times reported. Laboratory studies found that the variant was 40 per cent better at infecting human cells compared with earlier strains. In addition, people who tested positive for the California variant had twice the viral load in the nose and the throat than people infected with other previous USA versions of the virus.

This may mean that people infected with the California variant can also spread it more easily than people infected with other previous variants, according to the Los Angeles Times. Laboratory experiments also found that antibodies in people who had been infected with other variants of the novel coronavirus or who had been vaccinated against COVID-19 were two times less effective at neutralising or disabling the California variant. This variant, nevertheless, does not seem to be as dangerous as those of the South African, UK or Brazilian variants. In a recent study, scientists show that the new Indian variant has already been spreading in the Bay area of California in the United States.

David Ho of the Columbia University and his team reported in January 2021 that the monoclonal antibodies made by Eli Lilly, and one of the monoclonal antibodies in a cocktail made by Regeneron, are powerless against the variant identified in South Africa.

It needs to be clear to readers that the mutations mentioned above are not the only mutations in a variant referred to. For example, the Brazilian variant, in fact, has 17 point mutations in its genome and the UK variant 23, of which 17 are non-synonymous (new mutations) while six are synonymous (no new amino acids despite mutation). The notable point is that majority of these mutations occurred in the spike protein which helps the virus to enter a host.

In a study in South Africa on the people who were previously infected with the earlier variants of SARS-CoV-2, more than 90 per cent showed reduced immunity against the new variant and nearly a half had no protection against it, according to the USA Today. Studies on the P1 lineage of Brazil, however, found that previous infection with the variant prevents reinfection with it.

Although in the beginning it was presumed that the UK variant of concern is more transmissible but not deadlier, in January 2021, the British authority stated that the strain is up to 40 per cent more deadly while another paper in the British Medical Journal in March 2021 revealed that the variant was 64 per cent more deadly than the pre-existing strains. On the other hand, WHO estimates that the South African variant ‘increases the risk of death in hospital by 20 per cent.’

A new study, by Public Health England and Birmingham University, may have discovered why the new coronavirus strain spreads more quickly — it replicates faster in the throat compared with the original virus. Samples taken from the nose and the throat of patients diagnosed with the new variant of COVID-19 were found to have a ‘high viral load’ compared with those who had the original virus.

Preliminary data suggest that the growth rate and the effective reproductive number were elevated in areas of the United Kingdom with community circulation of the novel variant VOC-202012/01 (B.1.1.7). In South Africa, genomic data highlighted that the 501Y.V2 (B.1.351) variant rapidly displaced other lineages circulating, and preliminary studies suggest the variant is associated with a higher viral load, which may suggest potential for increased transmissibility; however, this as well as other factors that influence transmissibility is subject of further investigation. While an initial assessment suggests that 202012/01 (UK) and 501Y.V2 (S Africa) do not cause changes in clinical presentation or severity, a higher case incidence would lead to an increase in COVID-19 hospitalisation and death.

As has been revealed from the genomic sequencing since January 2021, the South African variant now seems sprawling fast in Bangladesh, surpassing that of the UK variant. New RT-PCR test profiles give rise to the doubt of expansion of the Indian variant in Bangladesh also.

Effects of vaccines against new mutants

MOST of the currently approved vaccines around the world might evoke an immune response to some extent against multiple variants although only Johnson & Johnson’s Janssen vaccine has been found to be 57 per cent effective in South Africa amidst the new variant and AstraZeneca 10 per cent. A recent study on the people vaccinated with Moderna’s COVID-19 vaccine found that the levels of antibodies produced in response to the South African variant were six-fold lower than levels produced in response to other variants, according to the Scientist. On the other hand, no trial has yet been undertaken on the effectiveness of vaccines against the new Indian mutations.

Apparently the transmission loop has not been affected by the current vaccines in India and cases are surging by leaps and bounds in the country, so is the number of death. Under the prevailing conditions, the expected herd immunity will be difficult to attain. It is, however, suggested that although the vaccines may prove to be weak in breaking the transmission chain, they nevertheless would reduce the rate of hospitalisation and death. It is thought that wider and faster vaccine coverage across the world might reduce resistance to vaccines by the new and future mutants.

Side effects of vaccines

SOME people have been reported with side effects after vaccination against COVID-19. AstraZeneca jabs were found to produce antibodies that activated platelets (a blood component involved in blood clotting) of the vaccinated people. However, researchers did not know yet why blood clots occurred in the vaccinated. Based on the findings, they concluded that the AstraZeneca vaccine (ChAdOx1 nCov-19) can result in the rare development of thrombocytopenia (reduction of thrombocytes in blood) through an autoimmune mechanism which produces antibodies against platelet factor 4, mimicking a heparin-induced thrombocytopenia (the New England Journal of Medicine).

This is the phenomenon observed in dengue haemorrhagic fever/ dengue shock syndrome also. This also indicates that heparin, the blood thinner for treating clots, would rather be more dangerous to treat these clots with. In the past week, Johnson & Johnson’s Janssen vaccine was also found to create blood clots in the vaccinated, which prompted the suspension of the vaccine in United States. Reports on post-mRNA vaccination related deaths and facial paralyses are noticeable. These occurrences might soar the vaccine hesitancy mentality among people.

Covax saga

COVAX was established in 2020 to promote the supply of vaccines to countries that might face problem in obtaining them. One hundred and ninety-two nations joined it. Each was promised enough jabs to inoculate 20 per cent of its people. Oxford-AstraZeneca had an understanding with the Serum Institute of India to sell the vaccine produced under a licensing system by the former, at $4/5 per dose, and to sell to Covax as a priority. But on March 24, 2021, India put a temporary halt on vaccine exports after some initial supply had been made to some African countries directly and through Covax and to Bangladesh. As it was supposed to provide 86 per cent of supplies for Covax, this has thrown the Covax promise into a whirlwind. For an undisclosed reason, the Organisation of African Unity of 54 countries has taken back its advance to the Serum Institute. A recent communiqué has, on the other hand, revealed that United States and the United Kingdom have stopped delivering raw materials to Serum Instittute.

How to reduce surging number of death

BANGLADESH has recorded a high number of death in recent times, the cause of which has been explained above. Questions are raised on how the number of death may be reduced. First of all, the more the infection, the more will be the death among those who are at higher risk of dying. It is warranted that those who are at greater risk of dying — frail and elderly people and people with comorbid conditions including obesity and smoking habits — are accosted repeatedly to encourage them to keep their conditions under control.

It is also necessary that the people at greater risk are cut off under the prevailing condition from the in-family members who have to go out of home almost daily. The people at higher risk, with the first sign or suspected of COVID-19, should be tested immediately and if they are positive, they should be sent to hospital before even respiratory distress develops in them. Vaccines in older age group theoretically do not bolster immunity much, but still it is not a bad option. People at risk should also work towards improving their immunity by, for example, bathing in the sun (not between 11:00am and 3:00pm though) for boosting their body store of Vitamin D and also eat adequate amount of Vitamin C and Zinc and protein (protein is necessary for our immune system to function effectively) and undertake some exercise, which also strengthens immunity.

Govt notifications may be more well researched

PUBLIC notifications issued by the government may be formulated involving all concerned, after sufficient thoughts and visualised for their various implications and implementability. Changes in them after issuing, diminishes public faith and respect for them, with unpleasant fallout. The recently issues lockdown notification had to be modified first to accommodate the need for foreign exchange and then the realisation came that to facilitate this, banks will also have to remain open. Then there came the optimality of issuing movement pass.

We cannot appreciate why food shops will remain open from 12 noon to 7:00pm? Is it necessary to keep food shops open for lunch when people are not supposed to foray out and when even government offices would remain closed? Should collecting lunch, when nobody is expected to stay out of their homes, under any pretext be a pretext for people to venture out? Already registering for a movement pass has hit a snag as the servers are clogged. Besides, how many people will collect lunch from food outlets under the stringent conditions? Will it be efficient on part of the management of these outlets to keep their outlets open for a few?

We believe only raw food items should be allowed to be purchased and for which people may be allowed to go out but as close as possible to their homes for which, a window period of 9:00am to 3:00pm has been provisioned — too long a period to be allowed. The procurement of essential items is always an urgent issue and people should not really need more than two hours for this. Emergency situations cannot be defined in terms of time and hours. Food shops may remain open from 4:00pm to 7:00pm for buying iftar and other food that time, with an advice to the people to stay at home as much as possible even within these hours.

Abu Muhammad Zakir Hussain is a former director, Primary Health Care and Disease Control, former director of the IEDCR, DGHS, former regional adviser of SEARO, WHO and former staff consultant, Asian Development Bank, Bangladesh.