Covid variants (strains) and anticipatory third wave
Asha Shah.M.D
Professor of Medicine
GCS medical college,Ahmedabad
Introduction
Now a day’s every news media is talking about third wave and Delta plus. People are naturally concerned. We have seen a very bad second wave. In this dangerous play, there are two players, virus and people. Unfortunately both were to blame in the second wave. There was disregard of Covid appropriate behavior and virus also mutated. Delta virus was detected in our country which turned out to be more transmissible. So there was rapid rise of peak and people were caught unaware. The cases started decreasing also suddenly but the wave had taken a very heavy toll and so many people succumbed to the illness. It was a horror unlike any we have ever seen. Before we talk about third wave, we should remember that second wave is still not over but it is a huge relief that cases are significantly less.
Viral Mutation
We keep on hearing the various mutations happening in the Covid virus and people are fairly aware of the various variants like Alpha, Beta, Delta etc. Medical knowledge of non medical people is also significantly more. Even general public talks about RT-PCR , DNA, RNA, Immunity, CT value and CT score etc. This pandemic has made people more aware about health system and it is a very welcome change. In the long run, it will definitely help people to be more cautious and aware of their health. Ideally we would expect that but it is not happening. As soon as the lock down is lifted, people have started behaving the same way as they did before the second wave. Can’t we learn anything from the terrible scenario we witnessed just few weeks before? It is responsibility of the whole community to continue taking all due care. We cannot afford to let our guard down. This Corona virus is unlike any that we have ever encountered in the past.
Mutation is the property of a virus to undergo changes when it multiplies. As it replicates, it may not produce exact replicas of itself, resulting in the emergence of new strains, which may be more or at times less effective. Some strains die out, while the more effective ones, which spread efficiently, survive. Viruses constantly change through mutation, and new variants of a virus are expected to occur. Multiple variants of the virus that causes COVID-19 have been documented globally during this pandemic .The first important mutation noted were D614G mutation in April 2020. It had rapidly become the dominant SARS-CoV-2 lineage in Europe and had then taken hold in the United States, Canada and Australia. D614G represented a more transmissible form of SARS-CoV-2.By the end of June it was seen worldwide.
A virus that has got a mutation in it is known as a variant
Important variants:-
B.1.1.7 (Alpha): This variant was initially detected in the United Kingdom.
B.1.351 (Beta): This variant was initially detected in South Africa in December 2020.
P.1 (Gamma): This variant P.1 was initially identified in travelers from Brazil, who were tested during routine screening at an airport in Japan
B.1.427 and B.1.429 (Epsilon): These two variants were first identified in California in February 2021.
B.1.617.2 (Delta): This variant was initially identified in India in December 2020.
Lambda
As per the World Health organization(WHO), the Lambda variant or C.37 was first found in Peru in December 2020. WHO designated the variant earlier this month. The variant is believed to be widely prevalent in Peru.
A US government inter agency group developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants:
Variant classification
These are as follows
-Variant of concern
-Variant of interest
-Variant of high consequence.
Variants of interest
A variant with specific genetic markers and is associated with changes to receptor binding.
It has reduced neutralization by antibodies generated against previous infection or vaccination and also has reduced efficacy of treatments.
It has potential diagnostic impact
There may be predicted increase in transmissibility or severity of the disease
Possible characteristics of a variant of interest:
- Specific genetic markers that are predicted to affect transmission, diagnosis, treatment, or immune escape
- Evidence that it is responsible for an increased proportion of cases or unique outbreak clusters
- Limited prevalence or expansion in other countries
A variant of interest would need appropriate public health actions, which would include enhanced surveillance, enhanced laboratory characterization and enhanced epidemiological investigations to know how easily the virus spreads to others, the severity of disease, the efficacy of available therapies and if currently authorized vaccines offer protection
B.1.525,WHO label Eta first seen in UK and Nigeria, B.1.526 named Iota seen in US, B.1.617 seen in India, B.1.617.1 named Kappa also seen in India,P2 named Zeta seen in Brazil are some of the variants seen in late 2020 or beginning of 2021.
Variant of Concern
A variant for which there is evidence of an increase in transmissibility,
More severe disease (e.g., increased hospitalizations or deaths),
Significant reduction in neutralization by antibodies generated during previous infection or vaccination,
There is supposed to be reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
Possible characteristics of a variant of concern:
In addition to attributes of a variant of concern
- Evidence of impact on diagnostics, treatments, or vaccines
- Widespread interference with diagnostic tests
- Evidence of significant decreased susceptibility to one or more class of therapies
- Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination
- Evidence of decreased vaccine-induced protection from severe disease.
- Evidence of increased transmissibility
- Evidence of increased disease severity(Increased hospitalization or death)
Variants of concern might need appropriate public health actions, such as notification to WHO under the International Health Regulations, local or regional efforts to control infection spread, increased testing and research to know the effectiveness of vaccines and treatments against the variant. It may include the need for development of new diagnostics or the modification of vaccines or modify treatments.
The following are the variant of concern
B 1.1.7 or WHO labeled it Alpha, first identified in U.K
Characteristics
- There was~50% increased transmission
- Potential increased severity based on hospitalizations and CFR(case fatality rates )
- No impact on susceptibility to EUA(Emergency use authorization) monoclonal antibody treatments
- Minimal impact on neutralization by convalescent and post-vaccination sera.
B.1.351 or WHO named it Beta, first identified in south Africa
Characteristics
· ~50% increased in transmission rates
· Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment, but other EUA monoclonal antibody treatments are available
· Reduced neutralization by convalescent and post-vaccination sera
B.1.427 or WHO label Epsilon originated in USA California
Characteristics
- ~20% increased transmission
- Modest decrease in susceptibility to the combination of bamlanivimab and etesevimab; however, the clinical implications of this decrease are not known. Alternative monoclonal antibody treatments are available.
- Reduced neutralization by convalescent and post-vaccination sera.
B.1.617.2 or WHO labeled it Delta first identified in India.
Characteristics
- Increased transmissibility
- Potential reduction in neutralization by some EUA monoclonal antibody treatments
- Potential reduction in neutralization by post-vaccination sera.
The head of the World Health Organization said the COVID-19 delta variant, first seen in India, is “the most transmissible of the variants identified so far,” and warned it is now spreading in at least 85 countries
Delta plus B.1.617.2.1/(AY.1) new K417N mutation in spike protein ,first detected in Europe
Since it’s a new variant, its severity is still unknown. It is likely to be more transmissible.It has stronger binding to receptors of lung cells and potential reduction in monoclonal antibody response or antibody cocktail treatment.
Health officials say that this sub strain is unlikely to cause much havoc in India as data from other 9 countries where the wave is ongoing are insignificant.
P.1 or WHO label Gamma originated in Brazil.
Characteristics :
- Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment,but other EUA monoclonal antibody treatments are available
- Reduced neutralization by convalescent and post-vaccination sera
Variant of High Consequence
A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.
Possible characteristics of a variant of high consequence:
In addition to the possible characteristics of a variety of concern
- Impact on Medical Countermeasures (MCM)or measures to control the spread
- Demonstrated failure of diagnostics
- Evidence suggesting significantly reduction in vaccine effectiveness, a disproportionately high number of vaccine breakthrough cases(having disease in spite of full vaccination ), or very low vaccine-induced protection against severe disease
- Significantly reduced susceptibility to multiple Emergency Use Authorization (EUA) or approved therapeutics
- More severe clinical disease and increased hospitalizations
A variant of high consequence would require notification to WHO under the International Health Regulations, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines.
Thankfully currently there are no SARS-CoV-2 variants that rise to the level of high consequence and let us hope that it remains like that. If the entire world was and probably still is in such a chaos with all the variants of concern, it is unimaginable what would have happened if there was a variant of high consequence. That is why it is imperative to take all the measures to control the cases and to take all the preventive measures by all the concerned parties because we don’t want to be caught unaware again.
Possible third wave
Regarding the third wave and all the speculations surrounding it, It may come or if we are very optimistic, may not come. The possibility of third wave is likely as it is happening in countries like U.K where already more than 10000 cases are recorded per day. The speculation that children will be more affected in third wave also remains controversial. Data collected by AIIMS between March 15 and June 10, 2021, from over 4,500 participants across four states, found sero-prevalence in 55.7 percent samples collected from individuals aged between 2 and 17 years, and in 63.5 percent among adults.“There was no statistically significant difference in prevalence between adults and children,” the AIIMS study noted.
Till now the severity in children was very less and we have currently no large scale data on the prevailing antibodies in the community and in different age groups though ICMR was going to start sero survey in June. The last sero survey (Third) done in February 2021 showed that 21.5% of adult population was exposed to Covid 19, but this was before the infamous second wave and now we also have large number of people being vaccinated. The chief of the Covid-19 working group of our country said that the next wave of Covid 19 may be delayed until December this year as per ICMR .In a study published in another journal it was also predicted that third wave will not be as severe as the second wave. While a study done by IIT Kanpur has predicted three scenarios and the timing predicted is peak in September and also predicted the peak will be larger than second wave. All of these studies have many variables though and whatever the predictions and presumptions, corona virus has proved them all wrong mostly. Our government has announced that Delta plus, is a “variant of concern”. but we are not sure to say that it could cause a third wave as we need more data.
The factors which will decide about the possible third wave are
Behavior of Delta plus variant or any other possible mutation
Covid appropriate behavior of people
Rate and speed of Covid vaccination in India
Prevailing antibody level in community
Possible vaccination of children by the vaccine if approved
Any possible unknown variable
One thing we have learnt in this pandemic is the certainty of uncertainty. There are so many things we are still learning. The way corona virus is mutating and there is still ample scope to keep mutating, prediction can’t be certain. We will have to wait ,watch ,hope and pray
References :-
CDC website
WHO website
BBC news
