COVID19 Wins the Race for the Bomb

InfoMullet is collaborating with Science Decoded to bring a series of articles on COVID19. To view more of Science Decoded’s content including live-updates, Ask Me Anything videos, and even a few COVID19 related memes check them out on Facebook.

 

TLDRUpFront: A new variant SARS-COV-2 undermines current vaccines and is better able to reinfect people previously infected. It’s probably too late to stop the global spread of this strain. We still need swift, substantial action to slow the spread while we develop vaccines that work against the new strain.

FullContextInTheBack:

We are facing a new strain of COVID-19, able to evade the effects of an immune system already trained to fight other forms of COVID-19. This was the “Strategic Risk” explained in a previous InfoMullet.

 

In late 2020, a viral isolate was found in South Africa – also known as B.1.1.351, or COVID-19s1 – that was of grave concern^[6,7]. The isolate (then thought to be a variant by my definition, and now thought to be a strain by the same) rose quickly in prevalence in South Africa, coinciding with a surge of the virus across the country^[5,6]. (To help understand the terms: mutation, isolate, strain, and variant see this post on “Playing Darts.”) This suggested increased transmissibility, but did not prove it^[6]. Later tests showed that the isolate also decreased the binding efficiency of the antibodies present in convalescent plasma from people previously infected with COVID-19^[5,8]. Other tests showed that the efficacy of the NovaVax vaccine in stopping it was substantially reduced (down to 50-60%), relative to other forms (that were 85-95% effective)^[13]. Tests on the plasma of people who has received the Pfizer or Moderna vaccine demonstrated that the binding efficiency of the antibodies in it was substantially reduced, when challenged by that isolate^[5]. Examination of SinoPharm and another Chinese-developed and licensed vaccine suggested similar^[9]. Further examination of the NovaVax trials suggest that persons previously infected with COVID-19 also have little protection against that isolate, while retaining a significant degree of protection against others^[14]. Finally, South Africa has halted its rollout of the AstraZeneca vaccine in light of substantially compromised protection against COVID-19s1^{[10,11,12,20]}. When looking at the mutations (N501Y, K417N, E484K)^[6] in this isolate, two – N501Y, K417N – are associated with increased binding efficiency to ACE2 receptors^[1,6], suggesting that they make it more transmissible than other versions of the virus. One – E484K – appears to account for its escaping the effects of neutralizing antibodies^[16], though N501Y may also perform this function^[15]. That same mutation is found in isolates of SARS-COV-2 found in Japan and Brazil, though those lack some of the other mutations^[2].

This strain has subsequently been found in more than 30 countries – several in the EU, the UK, Israel, and in South Carolina^[17], Virginia, and Maryland in the United States^[19], Kenya, South Africa (obviously), the United Arab Emirates and Japan^[16,18]. Other isolates that also have the E484K mutation that make them likely to fall under the COVID-19s1 umbrella have also been found in Brazil, Japan, and elsewhere.^[2]

How’d we lose the race for the bomb?

Well, first: viral mutations just happen^[3,21]. They are intrinsic to viral replication, so some degree of mutation is both expected and normal for a virus. However, the more times the virus replicates – that is, the more people it infects – the more proverbial darts get thrown at the equally proverbial dart board.

So, as I have said before: we beat a disease by beating the disease. We don’t give it space, we don’t compromise with it, we don’t try to do public health on the cheap… we just beat it. The more space we give it in which to operate, the more likely it will grow more dangerous to us over time.

Additionally, the development of several variants/strains seems to be driven by a specific “perfect storm” of circumstances^[4]. That is: a patient with a compromised immune system, being given the best normal medical care possible; an infection that lasts several months despite those best efforts; and imperfect infection control practices (likely helped by overwhelmed health care workers, who are themselves exhausted) that allow their disease to spread to others. Within that perfect storm, the evolutionary pressures on the virus – to survive, evade the effects of the treatments given to eradicate it, and infect now-less-susceptible cells in its host – strongly select for the exact sorts of mutations that give rise to new variants and new strains. They don’t make the underlying processes any more “smart,” but they do massively increase the rewards for getting lucky, and give the virus more time in which to throw more darts out and try to hit the bullseye.

 

From Nuclear Weapon Prevention to Nuclear Weapon Containment: Living with a new COVID19 Variant

This ultimately happened because we did not adequately protect the immunocompromised among us, and we overwhelmed our health care system both in the short term (through the December surge) and the long term (by not adequately controlling the pandemic from the start). Developing a solution from that starting point is relatively straightforward, though the task itself is rather massive and rather complex. Here are the pieces.

First, we desperately need to reduce the total number of COVID-19 infections – whether COVID-19s0 or COVID-19s1 – happening globally. Numbers are coming down in many places, but when I say we need to reduce the total number I do not mean relative to what we are seeing now but in absolute terms. Better is better than worse, but we are still a long way from anything that could fairly be called “good.” When the world’s per capita daily case numbers start to look less like Sweden and more like New Zealand, then we will be getting somewhere… but until then, we are still adding too much heat to the crucible that forges these new strains.

Aside: You might be surprised that the strain seen thus far rose to prominence outside of the United States, but simple math shows why that was likely always going to be the case. While the United States bears the burden for ~20-25% of global cases of COVID-19, that means the rest of the world bears the burden for the remaining ~75-80% of global cases. Thus, if a development like this was going to happen, it is much more likely that it would happen outside of the United States rather than inside of it, despite how badly we are handling the pandemic.

Next, we need to engage in some form of “load balancing” or other forms of health care optimization, in addition to expanding health care capacity in impacted areas (which right now is nearly everywhere). Yes, that will mean spending money on the task and it will take time, but the pandemic doesn’t seem to be going anywhere and there is plenty of incentive to act.  Borders ought not to be a barrier to this, because these “perfect storm” conditions are of global concern, so even if the hardest hit areas are in the middle of “enemy territory” we need to engage with them and give them the help they need to cool the crucible lest we wind up paying the price.

 

Next, we need to iterate our tools for everyone and in particular better protect the immunocompromised among us. That means developing and updating vaccines to protect against new strains, as well as swiftly and widely adopting vaccines so that we reach a level such that the immunocompromised are protected via known “herd immunity” pathways. We cannot afford to allow irrational levels of vaccine skepticism to compromise that protection; where we have reliable information that vaccines work, we must deploy them and not be afraid of invoking our most powerful – and most disruptive – tools to do so. We cannot afford to wait for the free market to settle this; we must act now.

 

Next, we need to update our treatment protocols to remove the final element of the “perfect storm” – transmission of new variants/strains from long-term patients to caregivers, and then to the community. We cannot and must not compromise the standard of care given to immunocompromised people when they contract COVID-19, but we have an obligation to the community to add new layers of protection around those patients, in order to protect everyone around them from the potential danger of the viral mutants circulating inside and around them.

 

Next, we desperately need to improve testing, contact tracing and isolation practices around COVID-19. This needs to be done for many more reasons than just fighting variants/strains of COVID-19, but the more readily we are able to identify and isolate exposed and infected individuals the less we will need to worry about them spreading. Given that many of these new variants – from South Africa, from California, from the United Kingdom, from Brazil – are substantially more contagious, this is of special and grave concern. As they take greater and greater hold, we will be required to do more to control them, lest they start growing at exponential rates in a curve of exploding oscillation that we have seen over and over again throughout the course of the epidemic.

 

Next, quite predictably, we need to restructure and improve our systems of public health interventions. That includes but is not limited to mask mandates, capacity limits, venue closures, public school closures and others. There are costs and tradeoffs to each of these, of course, and those costs need to be considered carefully when implementing those interventions in a local area… but the cost of doing nothing also needs to be kept in mind, since it is often quite significant. It is challenging and complicated to find the lowest cost way to implement sufficient, needed protections in a local area… but local leaders need to be engaged in that question, and consider updates and changes to reflect the new threat environment. Also, unlike with many other situations, this needs to be seen not as a compromise but as a necessity – you are not negotiating with the virus, you are trying to stop it in its tracks. Half measures will not accomplish that end.

 

Finally, we need to improve our systems of disease surveillance, to watch for these mutations to happen so that we know how to respond appropriately when they arise. The United States, despite its size, does advanced sequencing on relatively few viral samples – we need to fix that. At the same time as we increase the number of tests being given by a factor of 2-5, we need to increase the rate of sequencing being done ON those samples – sequencing being the advanced testing to identify a given viral isolate, rather than simply say a person is infected with some version of SARS-COV-2 – by a factor of 10-50. That will give us far more granular, and far more useful, information about the spread of various forms of the virus throughout the country, and better inform policy and public health decisions about how to handle those situations as they develop.

 

There is no world in which that does not cost money, and whether I like it or not there will be political challenges to implementing those policies. However, the other option – not doing them – is even more costly both in terms of dollars and lives. So, if for no other reason than simple self-preservation, we must pursue these objectives. Lives depend on it.

 

 

Sources:

1) https://www.biorxiv.org/content/10.1101/2020.12.23.424283v2 (two mutations that alter SARS-COV-2 affinity to ACE2)

2) https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2 (List of variants of COVID-19)

3) https://www.nature.com/articles/s41598-020-78703-6 (Recombination in SARS-COV-2)

4) https://www.npr.org/sections/goatsandsoda/2021/02/05/964447070/where-did-the-coronavirus-variants-come-from (Where did the COVID-19 variants come from?)

5) https://www.nature.com/articles/d41586-021-00121-z (Fast-spreading COVID variant cane elude immune responses)

6) https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1 (Rapid spread of COVID-19s1)

7) https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/ (WHO page on SARS-COV-2 Variants)

8) https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1 (COVID-19s1 escapes neutralization by donor plasma)

9) https://www.biorxiv.org/content/10.1101/2021.02.01.429069v1 (Neutralization of COVID-19s1 by post-vaccine plasma)

10) https://www.aljazeera.com/news/2021/2/7/astrazeneca-covid-jab-less-effective-against-s-africa-variant (AstraZeneca vaccine less effective against COVID-19s1)

11) https://www.aljazeera.com/news/2021/2/7/south-africa-suspends-astrazeneca-vaccine-rollout (South Africa halts vaccine rollout due to compromise efficacy)

12) https://www.reuters.com/article/us-health-coronavirus-safrica/south-africa-puts-astrazeneca-vaccinations-on-hold-over-variant-data-idUSKBN2A70PY (South Africa halts vaccine rollout)

13) https://www.nytimes.com/2021/01/28/health/covid-vaccine-novavax-south-africa.html (NovaVax trial data)

14) https://www.washingtonpost.com/health/2021/02/05/virus-variant-reinfection-south-africa/ (NovaVax and Reinfection)

15) https://www.biorxiv.org/content/10.1101/2021.01.22.427749v1 (Variants that reduce neutralization sensitivity to monoclonal and seral antibodies)

16) https://www.bbc.com/news/health-55534727 (What is the risk from COVID-19s1?)

17) https://www.washingtonpost.com/health/2021/01/28/south-africa-variant-south-carolina/ (COVID-19s1 seen in South Carolina)

18) https://www.theguardian.com/world/2021/feb/01/what-we-know-about-the-south-african-variant-of-covid (What we know aboutCOVID-19s1)

19) https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html (CDC Case map for variants of COVID-19 in the United States)

20) https://www.nytimes.com/live/2021/02/07/world/covid-19-coronavirus (AstraZeneca does not work well against COVID-19s1)

21) https://www.newscientist.com/article/2266429-uk-coronavirus-variant-gets-nastier-as-south-african-variant-spreads/ (B.1.1.7 mutates as COVID-19s1 spreads)