By Dr Edward Nazareth
Dec 28: As we are approaching the end of the year 2020, the mutated COVID19 virus is creating havoc in the United Kingdom and in other European countries. The daily number of positive cases is steadily rising in the United States. The problem in USA doesn’t seem to be related to the mutated strain. Fresh lockdowns are imposed in many of the countries all over and most of the world is anxiously waiting for an effective vaccine to save us from this deadly virus.
But overall, numbers in India are falling — for reasons not yet fully clear. Though the authorities are warning to be cautious, people in India seem to be care free. There is a general feeling that we are out from the clutches of COVID19 virus. Many people including some experts believe that the mutated virus may not affect us.
Why did the COVID 19 virus mutate? Does this affect the tests and vaccines? Is the second wave related to mutation or human behavioural fatigue? - These are some issues which are of interest now.
Viruses mutate for existence
Mother Nature supports all living beings to safeguard their existence. Natural selection has shaped the evolution of humans, plants, and all living things on the planet; similarly natural selection shapes viruses, too. The viruses do not have life by themselves, they need a host organism to establish their existence and reproduce. There are mainly two types of viruses-DNA virus and RNA virus. Small pox, herpes, human papilloma virus are examples for DNA viruses. Common cold virus (Corona virus), influenza, HIV is some of the RNA viruses. RNA viruses are known for mutation where as the DNA viruses are more stable.
To understand the process of mutation, let us take the corona virus that produces common cold. The corona virus also depends on human beings to survive and multiply.
The corona viruses enter the nasal mucosa. They have spiked proteins sticking out from their surfaces, and these spikes hook onto the cell membranes of the host. The genetic material of the virus then enters the human cell. Once inside the host cell, it hijacks the genetic material of the host cell and multiplies-the genetic material of the host turns into the genetic material of the virus. It steals the life of the cell and uses it as its own!
But the human system does not sit quiet. It has the immune system which produces the antibodies to eliminate the viruses. Antibodies lock onto the outer surface proteins of the virus and prevent it from entering host cells. The antibodies are specific. The antibodies against corona viruses of common cold can detect only these specific viruses by their spike proteins.
The spike protein may be compared to the uniform of the enemy. The enemy is identified by the antibodies in the host (human) system based on its uniform.
The virus also has to find a way to survive. The viruses alter their spike proteins during in the process of multiplying! Large numbers of new viruses are formed with altered spike proteins. It is like same old enemy army with a new uniform. This characteristic of the viruses is known as ‘MUTATION’.
The human immune system might not be able use its antibodies against the mutated virus effectively.The antibodies produced by previous infection by the original strain or by the vaccine developed for the original strain may not fight the mutated virus with the same efficacy. As a result, the same virus with altered spike proteins can infect the host again and may result in illness.
Thus, mutation is a survival tactic that helps the ‘lifeless’ viruses to survive and multiply. This is the reason why we get frequent common cold by these viruses. There are several strains of these and they mutate to produce new ones.
The COVID19 virus also belongs to the family of corona viruses and it also needs human host for its survival. The corona viruses are not the only one which mutate. Mutation is common in most of the RNA viruses that infect humans as well as other living organisms.
COVID 19 has many mutations
As explained above, mutation means an alteration in genetic material; (The genetic material is a protein). The genetic material or genome of COVID 19 virus is a ribonucleic acid (RNA) made up of over 30,000 base pair or units (called nucleotides). These are like the bricks placed one over the other to form a structure.
Among the families of RNA viruses, the corona viruses have the largest genome. Most other RNA viruses have on average about 10,000 units. When genomes replicate (or multiply) mutations take place. An alteration in these base pairs (like the bricks of a structure) can effectively change the shape and behavior of the virus. In simple words, mutation is like changing one or more bricks from a structure. By mutation, the virus can become more powerful or can lose its potency.
The mutation of COVID19 in the United Kingdom has made the virus more capable to bind with human cells which mean they are more infectious. The mutated strain is called N501Y.In simple words, the amino acid represented by the letter N, and present at position 501 in the genetic structure of COVID19 virus, has been replaced by another amino acid, represented by Y. This alteration has taken place in the spike protein that binds with the human cells. (To make it simple a brick at position 501 is replaced by another, and the virus behaves differently). The mutated virus reportedly accounts for 60% of recent infections in London. The mutated strain first spotted in the UK is spreading to more parts of the world. This strain has been identified in Germany, Switzerland and Japan. Earlier, Denmark, Netherlands, Australia and Belgium had found the UK-linked variant.
The mutation in Nigeria is known as P681H. This mutation has occurred in the amino acid present at position 681 in the spike proteins. Here the amino acid P has been replaced with H.
There is one more variant known as HV 69/70. In this mutation the amino acids at positions 69 and 70 have disappeared (known as deletion). These positions are again in the spike protein of the virus. (The bricks are removed, not replaced) This mutation has been observed in France and South Africa as well. This double deletion has occurred many times and likely to change the shape of the spike protein.
Several mutated strains are also found in India. Most common one is D614G, again a mutation in the spike protein of the virus. The name D614G encodes the names of the amino acids at the 614th position. This particular mutation changes Aspartic acid (D) at the 614th position to Glycine (G).
There can be many similar mutations in the coming days world over. The European Centers of Disease Control (E-CDC) has said that as per “molecular clock estimates”, the COVID 19 virus has been mutating at a rate of two changes per month.
Mutations-effects on tests
As explained above, mutations are blessings for the viruses to survive. Because of vaccinations and growing immunity in human populations, the viruses mutate so that they spread more easily, or they escape detection by the immune system of the host.
Though the existing RT-PCR test could detect variant strains, it is possible that new strains may go undetected by some of the other tests. The tests based on the spike proteins may be affected because of the deletion at positions 69/70 of the spike proteins. However as most of the RT-PCR assays worldwide use multiple targets, the impact of the variant on diagnostics may not be significant. This opinion is expressed by CDC as well as WHO (World Health Organization).
Mutation and existing vaccines
Though the RNA viruses cause many animal, human, and zoonotic diseases, so far vaccines are not used extensively against these including HIV infection. Although efficient vaccines are available for some RNA viruses, in many instances and for different reasons (technologic restrictions, cost, etc.), they are not widely used in the field, and, even more, for many of them, no licensed vaccines are available. Measles, mumps and rubella are three RNA viruses for which effective vaccines are available. These vaccines are prepared by attenuated (weakened) viruses. These three viruses are not as contagious as COVID19 and have no significant mutation. Moreover, the traditional technique of weakening the potency of the virus is used to prepare the vaccine. It is not prepared by modern methods used to manufacture COVID 19 vaccines.
The vaccines against COVID19 virus is probably the first vaccine which is manufactured using modern technology, trials were done rapidly and the vaccines are now used in beneficiaries at many places.
The experts have expressed some concern that the virus might evolve to become resistant to the existing vaccines. The worries are focused on a pair of alterations in the viral genetic code that may make it less vulnerable to certain antibodies.
Professor Ravindra Gupta, a virologist at the University of Cambridge, has found that the mutated virus was less susceptible to convalescent plasma from several donors than the original virus. That suggests it can evade antibodies targeting the earlier virus. This can seriously affect the several pharmaceutical firms which have spent a lot of resources on vaccine development.
The CDC has said vaccines approved by the US Food and Drug Administration (FDA) are ‘polyclonal’, producing antibodies that target several parts of the spike protein. It means that the vaccine will be effective even against the mutated virus. Theoretically it makes sense. ‘The virus may have multiple mutations in the spike protein to evade immunity induced by vaccines or by natural infection’ the CDC has said.
And the WHO has said that the laboratory studies were ongoing to determine whether these variant viruses had different biological properties or alter vaccine efficacy. The WHO has not found sufficient information to determine if this variant is associated with any change in severity of clinical disease, antibody response or vaccine efficacy. At present, the WHO is sitting on the fence.
‘COVID-19 vaccine is likely to fight off any mutation because they take place at one or two or at the most ten locations but the vaccine or the antibodies that are generated are against the entire virus. So, in principle, the vaccine will be as effective even with the mutated virus stream’ assured Dr. Shekhar Mande, Director-General of Council of Scientific and Industrial Research (CSIR), New Delhi recently.
This is a new virus, the vaccines have been developed using a new technology, these vaccines against COVID 19 virus has been tested for the first time and therefore it may be premature to come to any conclusion about their efficacy against mutated virus.
In principle, the viruses mutate to evade the antibodies. Will the COVID19 mutation succeed in this? -Only time will answer this question.
Second wave and mutated strain
The wave pattern in viral pandemic is not new. A pandemic wave is a rising number of sick individuals, a defined peak, and then a decline. The word “wave” implies a natural pattern of peaks and valleys; it warns that even during a lull, future outbreaks of disease are possible. Previous pandemics were characterized by waves of activity spread over months. This is seen in influenza out-breaks earlier. During the peak period, with adequate surveillance the diseases will drop below peak observed levels. After a certain period of ease, the additional waves will occur.
The horrific 1918 influenza pandemic, the ‘Spanish flu’ cannot be ignored when wave patterns of the pandemics are to be remembered. The current COVID-19 pandemic is often compared to this. The virus infected 500 million people worldwide and killed an estimated 20 million to 50 million victims—more than all the soldiers and civilians killed during world warscombined. The cases of Spanish flu dropped off over the summer of 1918, and there was hope at the beginning of August that the virus had completed its course. It was only the calm before the storm. Somewhere in Europe, a mutated strain of the Spanish flu virus had emerged, and it killed healthy young men or women within 24 hours of onset of illness. In the fall of 1918, the pandemic peaked during the second wave, which was highly fatal.
Insight from the past suggests that discrete waves result as a disease spreads into and out of a population. Different waves can have different features; regarding disease severity or which populations are most affected.
The mutated strain of COVID-19 in UK is said to be 70 per cent more infectious than the original strain. The mutation in the spike protein that clings to human cells is the likely cause of its increased transmissibility.It is not yet known whether it is more lethal than the previous strain.Similar to the situation in the UK, the appearance of the new variant led to a spike in infections across South Africa as well.
What causes the wave pattern is not clear. Some experts believe the theory, that the infected population develops some degree of herd immunity to the existing virus, which then undergoes a minor genetic change that allows it to recirculate and reinfect the population. This seems to be a logical explanation. There are study reports that the antibodies last from three months to eight months after infection. Disappearance of the antibodies after an infection (symptomatic or asymptomatic) can make the individual susceptible for reinfection.
One of the important issues of the pandemic is whether Covid-19 patients who have recovered once are still susceptible to the virus. While there were several reports of reinfections, the nature of the tests used to identify infections made it hard for scientists to confirm these events. The RT-PCR test, which is the current gold-standard for confirming whether a patient is infected with Covid-19, has a number of limitations. It is not always accurate, even if a person had recovered from Covid-19, many of them tested positive again, since the genetic material of the dead virus was still present in the blood. However, genetic sequencing tests confirmed the cases of reinfections. Two healthcare workers from Mumbai were infected by COVID 19 virus twice over a span of three months. Cases of reinfections are also found in the US, Hong Kong and Netherlands.
There could be a variety of reasons for the second wave in Europe and the US; the experts point to two important factors-a general lowering of guard after the numbers began to dip in the summer, and the drop in temperature that would be pushing most activities indoors. The cold, dry weather could also be helping the virus survive longer and remain potent, though the evidence on that is not conclusive.
At present there is no conclusive evidence to blame any factor for the second wave. It is not yet clear whether mutated strain is the cause for second wave. More studies may be needed to find out why we get wave patterns of infection in viral pandemics.
Let us be careful
At present we are witnessing a decline in the active COVID 19 cases in India. The mutated and more aggressive strain of COVID 19 strain of UK is not been found in India so far. We have to be extra cautious to see that this new strain does not enter the country, which may be impossible. Though the new strain is not more lethal than the original one, it spreads fast. That means, many people are infected, those infected produce and shed large quantity of viruses which leads to more person-to-person transmission. This can be really a big challenge, if the mutated strain of UK enters India.
Mutation in COVID19 virus can happen in India also. In India there are over 10 million confirmed infections and it is estimated that 150 to 200 million people are already infected. A fast spreader variant called 501.V2 emerged independently in South Africa. Similarly India too has a mutated strain termed P681H, which emerged in July and presently 14% COVID 19 cases are from this strain. Fortunately this is not a fast spreading strain.
As we step into 2021, we have to be cautious. The health authorities are warning of a second wave in the coming weeks. At the individual level, it is our personal responsibility to reduce virus transmission — less transmission means less opportunity for the virus to mutate.
And SMS is the only tool available with us now - Social distancing, Masks and Sanitization.