The Rapid Evolution of COVID-19: Cause for Concern, Reasons for Hope.
- The Story So Far
- Why We Should be Worried: Rapid SARS-CoV-2 Evolution
- What’s Causing the Evolution of More Dangerous SARS-CoV-2 Virus Strains?
- Three Key Selection Pressures Driving SARS-CoV-2 Evolution
- The Real-World Consequences of Rapid SARS-CoV-2 Evolution
- Some Reasons for Hope!
- Universal Coronavirus Vaccines
- Take-Home Message
- References and Further Reading
The Story So Far
We’ve been enduring the COVID-19 pandemic with lockdowns, social isolation, and economic uncertainty for a long time.
Now it may be hard to believe, but up until recently, we’ve been lucky on four fronts.
First, COVID-19 is (currently) far less lethal than either SARS or MERS (1).
Second, the early virus variants were not hyper-infectious. Because of this, we could control the spread of the virus using social distancing, mask-wearing, track and trace, and social isolation (2).
Third, effective vaccines were developed and deployed far faster than anyone thought possible (3).
Finally, children and young adults were largely unaffected by the early strains of the virus (4).
Why We Should be Worried: Rapid SARS-CoV-2 Evolution
Alas, things have recently taken a turn for the worse.
Like many, I hoped that the SARS-CoV-2 would become less virulent and evolve into another ‘common cold’ virus. Unfortunately, there’s no guarantee that a novel virus will attenuate. For example, smallpox remained a scourge to our species until we eradicated it through a global vaccination program.
Depressingly, SARS-CoV-2 now seems to be evolving into a more severe disease (5, 6).
What’s Causing the Evolution of More Dangerous SARS-CoV-2 Virus Strains?
Evolution is the result of three forces: replication, mutation, and selective pressure.
Replication is necessary for evolution because if an organism can’t replicate, it can’t survive. Therefore, the ability for an organism to replicate despite facing obstacles is the hallmark of successful evolution.
Viruses replicate at a fantastic rate. As a result, viruses ‘are the most abundant organism in the biosphere’ (7).
Every time a virus replicates, there’s a probability that an error will occur while copying its genomic material. These errors result in the creation of a mutant virus.
Because humans had no immune protection from SARS-CoV-2, the virus has replicated billions of times across the globe. Unfortunately, this vast replication has created many new viral mutants.
Further, the genome of the SARS-CoV-2 virus is made of RNA. Because RNA replication is more error-prone than DNA replication, RNA viruses mutate rapidly, enhancing their ability to generate more dangerous virus mutants (8).
The critical point is that mutation creates new strains of the virus with improved biological properties compared to the original virus.
Think of Wolverine and his super-healing ability as an example of how mutation can lead to a new and beneficial biological property.
In the world of viruses, new SARS-CoV-2 ‘superpowers’ include becoming more infectious, causing more severe disease, and evading your immune response.
Finally, there’s selection pressure.
Selection pressures are those natural obstacles that prevent an organism from replicating.
Organisms overcome selection pressures by acquiring new properties via mutation. In the context of SARS-CoV-2 evolution, mutant virus strains such as the delta variant have developed biological properties that allow them to overcome selection pressure and continue to replicate.
Three Key Selection Pressures Driving SARS-CoV-2 Evolution
1. Competition between virus strains
All things being equal, more infectious mutants of a virus will spread faster than mutants with lower infectivity.
Because the different mutant SARS-CoV-2 strains are in direct competition, both within your body and within the population, the most infective mutant will usually win out and become the dominant virus strain. This is what’s happening with the current delta strain outbreak.
To better understand how self-competition drives rapid evolution, consider the case of Alpha Go. Alpha Go became the best Go player in history by using self-play.
In other words, different versions of the Alpha Go played each other, with the winner surviving to play a new variant. This self-play resulted in the incredibly rapid improvement in gameplay that allowed Alpha Go to dominate all human and computer opponents.
The phenomenon of self-competition helps explain why we are currently witnessing the emergence of more infectious SARS-CoV-2 mutants.
2. Distribution and prevalence of the host species
The evolutionary drive for increased infectivity raises the question: why don’t all viruses don’t mutate to become hyper-infectious and deadly?
One reason is that for most of our evolutionary history, humans existed in small, geographically isolated bands. Such geographical isolation imposed a strong negative selection pressure on the evolution of viral virulence.
This is because if a virus became too deadly, it wiped out its isolated human hosts, and then went extinct.
In this scenario, when novel viruses made the jump from animals into humans, they did so under conditions that strongly selected against the emergence of deadly strains.
However, this is no longer the case. There are now billions of humans living indoors, often in crowded conditions. Thus, our vast and tightly connected global population has created the perfect environment for creating highly infectious and virulent virus strains.
3. Our immune response
The third critical selection pressure is our anti-viral immune response.
We’ve all heard of herd immunity. Herd immunity occurs when most people within the population have mounted a protective immune response. When this happens, the virus can no longer infect enough new hosts to maintain its population.
Now, if herd immunity were perfect, then every virus would eventually go extinct.
Yet many viruses continue to persist within our population despite herd immunity. Why?
Because they mutate, creating new viral strains that our immune systems no longer recognize. These new strains can then re-infect the herd, and the cycle continues.
We are seeing this happen right now with the emergence of SARS-CoV-2 variants of concern (5).
The Real-World Consequences of Rapid SARS-CoV-2 Evolution
The threat now facing humanity is that the rapid evolution of the SARS-CoV-2 virus has produced variants of concern (VOC), such as the new delta variant (8). These VOCs contain new properties that make SARS-CoV-2 much more dangerous to our species. These include.
- Increased rates of infection in children, with possibly more severe disease (9-12)
- Increased rates of infection in adults (13)
- Increased viral load (14)
- Increased severity of illness and probability of death (15-18)
- The ability to avoid the immune response and cause disease in vaccinated people (i.e., escape variants) (17, 19-22)
Some Reasons for Hope!
The rapid evolution of hyper-infectious escape variants of SARS-CoV-2 has prompted politicians and advisory groups to accept the grim reality that COVID-19 is here to stay. For example, one health expert warns that ‘COVID will circulate among the population for decades to come’.
Is such pessimism warranted? I don’t believe that it is, and here’s why.
Universal Coronavirus Vaccines
The ideal SARS-CoV-2 vaccine would provide long-term protection against breakout SARS-CoV-2 strains, as well as protecting us from future coronavirus pandemics caused by new coronaviruses crossing over from animals to humans.
Vaccines that offer broad protection from different virus strains are called pan or universal vaccines (24). These are the holy grail of vaccines because the development of universal vaccines would protect us from past, present, and future coronavirus outbreaks (24).
Good news! There is now strong evidence supporting the possibility of creating universal coronavirus vaccines, as well as a clear path for making them a reality. Below, I highlight three recent breakthroughs in this exciting field.
1. The identification of broadly neutralizing coronavirus antibodies
Several groups have identified antibodies that neutralize SARS-CoV-2, escape variants of SARS-CoV-2, SARS-CoV-1 (the virus responsible for the first SARS outbreak in 2002), and a variety of bat and human coronaviruses (e.g. (25, 26)).
Why is this important? Because the existence of these broadly neutralizing antibodies shows that developing universal coronavirus vaccines is indeed possible.
2. The development of a pan-coronavirus vaccine in monkeys
Researchers have developed a nanoparticle vaccine that generates a broadly protective immune response against bat coronaviruses, SARS-CoV-1, and SARS-CoV-2 (including escape variants) (27).
Importantly for future vaccine development, the nanoparticle vaccine produced high amounts of neutralizing antibodies that completely protected the monkeys against infection from SARS-CoV-2 (27).
These findings show that a nanoparticle vaccine approach can generate long-lasting, universal protection against coronaviruses (27).
3. Pan-coronavirus immune protection in humans
Even more promising was the recent demonstration in Singapore of the generation of pan-coronavirus vaccine response in humans (28).
Survivors of the first SARS-CoV-1 coronavirus (i.e., SARS) received the current Pfizer mRNA SARS-CoV-1 vaccine. These patients developed high levels of antibodies that potently neutralized all the SARS-CoV-2 variants of concern.
Moreover, their serum also neutralized coronaviruses isolated from bats and pangolins that may cause pandemics in the future (28).
Thus, vaccinating people with the spike proteins from two or more coronaviruses may generate a universal immune response (28)! If true, this represents the fastest path for the development and deployment of universal coronavirus vaccines.
Alarmingly, SARS-CoV-2 is rapidly evolving into more dangerous variants with higher infection rates, more severe disease, the ability to avoid our immune response, and the capacity to infect children and young adults.
However, we are not doomed to live with coronavirus forever.
On the contrary, multiple research groups are now developing universal coronavirus vaccines. Universal coronavirus vaccines offer the hope of ending the current pandemic and stopping future coronavirus pandemics from ever occurring.
Please click on the link below to download your free PDF.
References and Further Reading
- E. Berber, D. Sumbria, N. Çanakoğlu, Meta-analysis and comprehensive study of coronavirus outbreaks: SARS, MERS and COVID-19. J Infect Public Health 14, 1051-1064 (2021).
- Y. Liu, C. Morgenstern, J. Kelly, R. Lowe, M. Jit, The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories. BMC Med 19, 40 (2021).
- H. Ledford, US authorization of first COVID vaccine marks new phase in safety monitoring. Nature, (2020).
- N. Rajapakse, D. Dixit, Human and novel coronavirus infections in children: a review. Paediatr Int Child Health 41, 36-55 (2021).
- Y. Liu et al., Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. bioRxiv, (2021).
- M. Ribes, C. Chaccour, G. Moncunill, Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain. Signal Transduct Target Ther 6, 164 (2021).
- M. R. Clokie, A. D. Millard, A. V. Letarov, S. Heaphy, Phages in nature. Bacteriophage 1, 31-45 (2011).
- A. M. Moustafa, P. J. Planet, Jumping a Moving Train: SARS-CoV-2 Evolution in Real-Time. J Pediatric Infect Dis Soc, (2021).
- A. Loenenbach et al., SARS-CoV-2 variant B. 1.1. 7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021. Eurosurveillance 26, 2100433 (2021).
- K. Dougherty, M. Mannell, O. Naqvi, D. Matson, J. Stone, SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility – Oklahoma, April-May 2021. MMWR Morb Mortal Wkly Rep 70, 1004-1007 (2021).
- Herlihy, R et al., Rapid Increase in Circulation of the SARS-CoV-2 B. 1.617. 2 (Delta) Variant—Mesa County, Colorado, April–June 2021 MMWR Morb Mortal Wkly Rep. 2021 Aug 13; 70(32): 1084–1087.Morbidity and Mortality Weekly Report 70, 1004 (2021).
- N. Erol, A. Alpinar, C. Erol, E. Sari, K. Alkan, Intriguing New Faces Of COVID-19: Persisting Clinical Symptoms And Cardiac Effects in Children. Cardiology in the Young, 1-27 (2021).
- J. Curran et al., Transmission characteristics of SARS-CoV-2 variants of concern Rapid Scoping Review. medRxiv, (2021).
- E. Teyssou et al., The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19. Journal of Infection, (2021).
- T. Nyberg et al., Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis. BMJ 373, n1412 (2021).
- N. G. Davies et al., Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature 593, 270-274 (2021).
- R. Herlihy et al., Rapid Increase in Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant – Mesa County, Colorado, April-June 2021. MMWR Morb Mortal Wkly Rep 70, 1084-1087 (2021).
- S. W. X. Ong et al., Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). Clin Infect Dis, (2021).
- K. D. McCormick, J. L. Jacobs, J. W. Mellors, The emerging plasticity of SARS-CoV-2. Science 371, 1306-1308 (2021).
- S. Mallapaty, Delta threatens rural regions that dodged earlier COVID waves. Nature 596, 325-326 (2021).
- K. R. McCarthy et al., Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 371, 1139-1142 (2021).
- Y. Cai et al., Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science 373, 642-648 (2021).
- E. P. Koen B. et.al., Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Open Access, (2021).
- S. Prakash et al., Genome-Wide B Cell, CD4(+), and CD8(+) T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines. J Immunol 206, 2566-2582 (2021).
- M. A. Tortorici et al., Broad sarbecovirus neutralization by a human monoclonal antibody. Nature, 1-9 (2021).
- T. N. Starr et al., SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature, 1-9 (2021).
- K. O. Saunders et al., Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature, 1-7 (2021).
- C.-W. Tan et al., Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors. The New England Journal of Medicine, (2021).
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Frailty is preventable, and often reversible, if you are willing to put in the work and follow the three golden rules of resistance training.
Frailty is preventable, and often reversible, if you are willing to put in the work and follow the three golden rules of resistance training.