COVID-19 fight in 2021: Fast and Furious and ahead of variants

Our current fight against COVID-19 has been led by scientists and biopharma companies who developed the first-ever mRNA anti-COVID-19 vaccines, in record time, and by regulators who approved them for emergency use in large regions of the world, also swiftly.  Many countries are now rolling out vaccination plans, for these and other vaccines, and as this text takes shape, over 63 million doses of anti-covid-19 vaccine shots in arms were performed in 56 countries.

Manufacturers continue to speed the development of new vaccine solutions and treatments for a growing number of individuals infected while all of us, around the world, have been living with more or less stringent social distance measures for several months and will have to continue to do so.

Still, SARS-CoV-2 already infected near 100 million human beings and caused over 2 million casualties.

What can we do differently to avoid such continuing catastrophe? Is new vaccine development stalled? Is production of already approved vaccines too slow for the world’s short-term needs? Are vaccination plans decelerated? Are lockdown measures taken too late and reactively?

Speed and urgency are our most precious assets.

Indeed, as we take time organizing our defenses, SARS-CoV-2 is spreading widely and at high speed, accumulating mutations and giving rise to new variants with the potential of bypassing some of our defense mechanisms (mutations are genetic changes; a variant is a virus with a specific new set of mutations).

In late 2020, new variants of concern of SARS-CoV-2 were identified.

Three different versions of the virus seem to have independently developed in three different regions of the world: the United Kingdom, South Africa, and Brazil.

These three variants have an array of mutations that are unique to each variant, but all three have in common a particular mutation in the spike protein, called N501Y. The spike protein is the protein the coronavirus uses to enter cells and the N501Y mutation seems to make the spike protein more adherent, allowing it to bind to and enter cells more promptly.

This is one reason why all three variants are more transmissible, why they have a clear advantage versus the original virus and why they are gaining more space at high speed, across the globe.

The UK variant (B.1.1.7, 20I/501Y.V1 or VOC 202012/01) has 16 other mutations that might benefit the virus in other ways. It is 50 to 70 percent more transmissible than the original virus and it is already present in over 60 countries. Currently, there is no consensus whether or not this variant causes more severe illness or increased risk of death, but there is some evidence that shows an increase in disease rates in individuals under age 20, although the reason for this is yet to be unraveled.

The South Africa (B.1.351 or 501Y.V2) variant was found to be 50% more infectious than the original strain and it has been detected in 20 countries since December. This variant has some mutations in the spike protein that are also present in the Brazil variant (also called P.1 or 20J/501Y.V3 or B.1.1.28 variant). One of these shared mutations, E484K, putatively confers both these variants the possibility to evade antibodies. This has been confirmed in recent studies with the South African variant. Indeed, this variant seems to escape substantially or even completely from neutralizing antibodies in plasma from COVID-19 infected people. Also, recent studies performed by Moderna seem to indicate that their vaccine is less efficacious in fighting the South Africa variant. What are the consequences of this? The development of new vaccines? More shots to reach immunity? What is the actual effectiveness of vaccines in this situation?

Currently, there is no consensual evidence if any of the three variants cause more severe illness or an increased risk of death, although recent preliminary results seem to indicate more severe disease and higher mortality associated with the UK strain. One thing seems to be clear, higher transmissibility means an increased number of covid-19 cases and a higher pressure on health care resources, leading to more hospitalizations, and potentially more deaths. Also, increased transmissibility rates might require a higher vaccination coverage to achieve the same level of population disease control, which means more people than anticipated would need to be vaccinated for herd immunity to be reached.

As time goes by, the risk of development of new, and maybe more aggressive, forms of the virus increase. These new variants might spread even faster, might cause more severe disease, might evade vaccine-induced antibodies and detection by diagnostic tests, or decrease response to treating monoclonal antibodies. All of these variants would be quite concerning, as vaccines could no longer be effective and reinfection could be possible, creating a higher risk for all, vaccinated or not, previously infected or not.

To win the fight against current and future variants, a single measure does not seem enough, and speed is key to stay ahead of the virus.

We need continuous, rigorous, and increased compliance with physical distancing, use of masks, hand hygiene, isolation, and quarantine.

We need a robust and global vaccination plan. No location should be left behind and unprotected as these could be ecosystems for continuous virus mutations that could spread aggressive variants worldwide again.

We also need across the globe and interconnected genetic vigilance of the coronavirus to early identify dangerous variants and act fast in case vaccine adaptation is necessary.

Time is of the essence.