From Volume 48, Issue 3, March 2021 | Pages 235-238
All viruses, including coronaviruses, change over time. This leads to multiple progenies of viral strains, with virulence traits that are unlike those of their parents. This article provides an overview of how viral variants emerge, and the signs and symptoms of variant-related COVID-19.
‘In the struggle for survival, the fittest win out at the expense of their rivals as they succeed in adapting themselves best to their environment.’
Owing to their constant replicative cycle, all viruses, including coronaviruses, change over time. This leads to multiple progenies of viral strains, with virulence traits that are unlike those of their parents. Since the arrival of the parental strain of SARS-CoV-2 from China over a year ago, it too has followed the natural Darwinian pathway of ‘survival of the fittest,’ leading to the production of three major strains/variants, currently in global circulation. These, the UK (Kent), the South African, and the Brazilian variants, with different geographical origins and sharing some of the mutations, are highly transmissible and equally deadly. Whether the variants are vaccine resistant is yet another major concern. Here, we provide an overview of how viral variants emerge and the signs and symptoms of variant-related COVID-19. The elucidation of the similarities and differences between SARS-CoV-2 variants should be helpful in developing future strategies to combat the pandemic.
Viruses are an evolutionary miracle. Mother nature has given them the infernal gift to evolve speedily from one generation to another to survive in adverse and hostile ecosystems, using the metabolic machinery of an unsuspecting host.1 This means ‘the fittest will survive’ the immunological assault once they infect a human, and generate more virulent and resilient new progeny than their forebears. In this manner, each new generation of viruses keeps one step ahead of the T and B cell-mediated immunological chase through subtle changes to their genomic and the antigenic profiles that allow evasion of the policing army of highly equipped immune cells.
Unravelling this phenomenon of viral evolution has baffled scientists for decades. Viruses adopt mutations and assortments of viral genes using the twin phenomena of antigenic shift and antigenic drift that allow avoidance of immune surveillance within a hostile host.2 Antigenic drift refers to the accumulation of a series of minor genetic mutations in the viral genome, from one generation to another. In contrast, an antigenic shift is defined as a radical change in the virus ‘genomic composition as a result of the ‘mixing’ of genes from two or more different viral species. These antigenic shifts usually occur inside a ‘mixing vessel’ or a ‘blender’, usually an intermediate host, such as a pig or a bat.
Antigenic drift is the reason why we need to take flu vaccines every year. Mutations can cause minute changes in the neuraminidase (NA) antigens on the surface of the seasonal influenza viruses, analogous to the Spike protein projections or S antigens of SARS-CoV-2 (Figure 1).3 Antigenic drift creates an increasing variety of strains until a new strain evolves that can infect people who are immune to the pre-existing strains. The new strain then replaces the older strains as it rapidly sweeps through the human population, often causing an epidemic, as opposed to a more widespread pandemic.1 As the strains produced by antigenic drift will be fairly similar to older strains, and some of the population will still be immune to them, the disease spread is relatively well contained. In contrast, when the viral genes reassort during an antigenic shift, they produce entirely new antigens, which baffles the immune cells attuned to the ‘older’ surface antigens. For this reason, all individuals exposed to the virus will now be susceptible, and the new viral ‘species’ can spread uncontrollably, causing a pandemic, as in the case of COVID-19 or the human immunodeficiency virus (HIV) pandemic that began in the 1980s.
For such reassortment of genes to occur a living and breathing, intermediate host is required as a ‘mixing vessel’ or a natural ‘viral blender.’ A good example is the viral gene reassortment in domesticated pigs, which leads to the generation of novel influenza viruses where the pigs serve as intermediate hosts for blending human, swine and avian influenza viruses.4 This phenomenon periodically occurs in China where pigs and chickens can be reared intensively at close quarters. Moreover, exotic animals, including civets, bats, and pangolins (ie the mixing vessels) may also be reared as food. Due to this combination of events, the newly reassorted virus may jump through species (eg bats, pigs) to another, humans, traversing the so-called species barrier.5
In the case of SARS-CoV-2, the ‘gene blending’ is thought to have occurred as an unfortunate accident where a fragment of genetic information from another unknown virus was mixed with the coronavirus carried by Chinese horseshoe bats (Rhinolophus sinicus), so called for their horseshoe-shaped nose, during a co-infective episode. This new genome possibly carried instructions that modified the spike protein (S) on the virus surface spikes that conferred a survival advantage when infecting not only bats but also humans (Figure 1). The spikes with this new S protein can effortlessly bind to cell surface ACE2 binding sites present in all human cells and cause COVID-19.6
Researchers have studied why SARS-CoV-2 is a ‘super’ infectious relative to its ancestral counterparts such as SARS-CoV-1, and MERS (Middle East respiratory syndrome) coronavirus, which caused epidemic rather than pandemic infections. They noted that the mutation in COVID-19 spike protein led to a curious effect. The spike protein could now hijack furin, an enzyme found in all human cells, which serves as a molecular scissors that, under normal circumstances, split hormones to activate them. However, when furin snips part of the SARS-CoV-2 surface spike protein, normally folded in a series of loops (Figure 1) on the viral surface, it opens like a hinge.7 The S protein's molecular hinge activity confers an incredible survival advantage because, once opened, the protein can latch onto a critical molecule, neuropilin 1, on the surface of human respiratory tract epithelial cells. Neuropilin 1 assists entry of the virus into cells where the virus replicates, leading to the highly transmissible infectious disease.8
A successful coronavirus life cycle in the host relies on critical molecular interactions with host proteins, which are either repurposed or hijacked to support the parasitic virus requirements. Additionally, viral survival depends upon an incessant intracellular replicative process to defend against the host immunological onslaught, leading to the systemic release of a successive progeny of multiple viral generations. During this process, genetic mutations occur due to mistranslation of their genetic code (resulting in ‘typos’ of the genetic sequence, as it were). This is the so-called genetic drift, mentioned above.
RNA viruses, such as coronaviruses, typically have higher mutation rates than DNA viruses.9 In most instances, the fate of a new mutation is determined by natural selection. Some mutants succumb, while others survive – ‘survival of the fittest’, giving the new progeny a competitive advantage in viral replication, transmission, and/or escape from immunity.10 These mutants are the so-called virus ‘variants.’ (Note: the terms mutant, variant and strain are often used interchangeably, although they do have precise scientific definitions, which are beyond the remit of this article).
Most of these variants have little impact, but occasionally a mutation occurs that produces a progeny with stronger infectivity, for example, in its transmissibility, as in the case of the British B117 variant of SARS-CoV-2. Currently, there are a number of variants causing infections globally, including the British, the South African, and the Brazilian variants, and other unknown emerging variants. Understanding the reasons for the emergence and the behaviour of such variants could prove essential for pandemic combat, and to evaluate vaccine efficacy.
Given below is an account of the currently known symptoms of the COVID-19 ‘variant’ infections, followed by a brief account of each of the three distinctive, significant variants – the British, South African and Brazilian variants – as well as the new variant B1.525, which is ill-defined at the time of writing.
Up to 40% of those who contract COVID-19 are asymptomatic.11 The remainder exhibit classic signs and symptoms of the disease, including a high temperature, continuous cough, and the loss of sense of taste or smell. As for the symptoms due to the new variants, early research indicates that the UK (B117) variant causes very similar symptoms to those of the parental strains. According to one report, 35% who were positive for the UK variant reported having a cough, compared to 27% who were positive for the original strain. One-third of patients (32%) who acquired the B117 variant reported fatigue, one-quarter (25%) had muscle aches, and one-fifth exhibited fever (21%) and/or sore throat (21%).12 Dysgeusia and anosmia were marginally low for those infected with the UK strain than those with the original strain (15% vs 18%) (Figure 2). These preliminary figures are likely to vary once data on viral variant-associated COVID-19 infections are analysed.
Given below are the significant features of distinctive COVID-19 variants circulating in the UK and the other regions of the globe.
The UK variant of coronavirus, B117, was first discovered in Kent in September 2020, and was linked to a dramatic increase in the number of COVID-19 cases in the UK. This variant is now a dominant strain in the UK and has spread to over 70 countries. It arose mainly due to H69/V70 deletion in the spike protein (Figure 1), a deletion now found in many other newer variants. However, the B117 variant has another sub-mutation (called N501Y) in its binding site with the cells, which appears to confer the advantage of tighter binding to ACE2 receptor sites on cell membranes, thereby increasing its infectivity and transmissibility. Additionally, it has been estimated that B117 replicates twice as fast as the original Wuhan strain.13 Hence, in terms of its spread, many believe that B117 will become the dominant form of COVID-19 in many countries, unless, of course, it is replaced by other newer variants or so-called ‘escape mutants’ in due course. A recent study has shown that B117 is linked to a higher likelihood of hospitalization and is up to 30% deadlier than the earlier versions of the virus.14
It is comforting to note that both the Pfizer/BioNTech and Oxford/AstraZeneca vaccines offer an adequate level of protection against mutations in the UK variant (B117). Up to 75% protection is offered by these vaccines to B117, which is very satisfactory because it is well above the 50% minimum level of protection recommended by the World Health Organization (WHO). For example, current annual seasonal influenza vaccines confer just above 50% protection.
Additionally, results from the Novavax vaccine clinical trial suggest it is almost as effective against the B117 as it was against the original strain.15 Although not currently available in UK, Novavax vaccine (a subunit vaccine), manufactured in England, is likely to be available in the autumn of 2021.
The South African variant, B1351, was the second variant that was detected after the UK strain. This strain, which is again highly transmissible, was seen first in South Africa and then in Zambia in December 2020, and currently, it has spread to over 20 other countries. At the time of writing, only a small number of cases of the South African variant has been detected in the UK, and the current lockdown and other government measures appear to have minimized its community spread. One reason for its high transmissibility is thought to be due to eight distinctive mutations in the spike protein.16 There is currently no indication it causes more serious disease.17
Early data on vaccine efficacy against this variant from a very small cohort indicate that the Pfizer/BioNTech vaccine offers adequate protection.16 However, another small study that included 2000 participants showed that the Oxford/AstraZeneca vaccine offers minimal protection against mild cases of the South African variant, and protection may be as low as 10%. As the study group was young and hence at low risk of serious illness, the researchers could not determine whether it protects against serious illness or hospitalization.18
A new strain of coronavirus, the P1 variant, first identified in travellers from Brazil, is now circulating in the UK, but it is not widespread. Although the Brazilian strain is not believed to be more deadly than the original Wuhan strain, it is much more transmissible, similar to the other variants described above. This variant has raised concerns that the virus may be developing an increased propensity for re-infecting individuals, according to the US Centers for Disease Control and Prevention.18
There is no good evidence to show the effectiveness of the Oxford/AstraZeneca vaccine against the Brazilian variant, and the results are awaited at the time of writing.18
This variant of coronavirus was discovered by researchers at the University of Edinburgh, UK, when they were examining coronavirus samples received from different parts of the world. Hence, this strain's geographical origin is unclear, although it is present in many countries, including the UK. The B1.525 variant has similarities to the B117 variant, having the identical E484K mutation, which is why it is more transmissible and more resistant to antibodies.
Additionally, it is unclear whether the B1.525 variant is more deadly or spreads more easily than other coronavirus strains or whether the Pfizer or Oxford/AstraZeneca vaccines will confer protection for those infected with the variant.18,19
There is already a bewildering array of coronavirus variants, and more are certain to be discovered and described in the immediate future. This high frequency of viral mutation and new variant arrival is likely to last as long as the pandemic lasts. The only way to prevent the emergence of the variants is to stop the pandemic in all regions of the world, no matter how remote they may be.
Thus far, one saving grace is that the currently circulating virus variants appear only to be more transmissible, but not deadlier, than the original Wuhan strain. The current COVID-19 vaccines and a number of others awaiting imminent arrival, together with critical public health measures, such as mask-wearing, personal hygiene, social distancing, and the resultant degree of herd immunity, should suppress the disease and the concomitant emergence of newer coronavirus variants. Dental care workers can play a crucial role here by rigorous adherence to all infection control policies, and informing their patients of the critical importance of vaccination, which is essential for returning to pre-COVID normality.
Unfortunately, a few ‘vaccine’ underserved population subgroups in any jurisdiction that are either neglected or negligent in vaccine acceptance may lead to a fierce resurgence of virulent, vaccine-resistant escape mutants that are likely to rekindle a secondary pandemic, leading to a recurrence of mass morbidity and mortality. Charles Darwin's prescient prophecy of the ‘survival of the fittest’ will then be borne true not only for the lowly viruses, but also for the whole of humankind.
