Some news stories suggest that if Omicron is mild it is a “blessing in disguise”. Should we let everyone get it as fast as possible? It might seem it would help - if Omicron is indeed a little milder, this may reduce pressure on the health system for a few weeks. However, large numbers of cases can still overwhelm us very rapidly - if it's half the severity, just one doubling of cases (which might take < 3 days) overcomes all that advantage for the health systems.,
Then, longer term this is not a safe strategy because mild variants can revert - or evolve to severe. We have no guarantee that Omicron will continue to become milder as it gets more transmissible - a more transmissible virus can go either way, more severe or milder. It's "much more random" as Dr Mike Ryan put it. We can make it mild with vaccines and therapeutics, we can even engineer mild variants for use as a live attenuated vaccine but we can't rely on it to go mild by itself.
Dr Tedros of the WHO warns that the virus can
"evolve in ways we cannot predict nor prevent".
Dr Mike Ryan says 40 minutes into the video.
"There is an assumption out there that as a disease becomes more transmissible it will become milder ... there's a little bit of an urban legend around that process. That doesn't necessarily happen.
... The outcome of whether a virus is more or less severe is much more random. It can happen, it can not happen and in that sense that's why we don't know and I think we have to be very, very careful in making any absolute determinations."
For longer transcript and key points see : Urban legend that viruses evolve to be mild (below)
Live vaccines are designed to stay mild but Omicron could evolve either way
Opens the door to a new landscape of mutations
Need vaccines + masks + #DOITALL to end the public health emergency
Milder variants aren't a substitute for
- well designed vaccines
- rapidly and equitably distributing the vaccines globally to everyone who needs them -
- #DOITALL as much as possible to break transmission and slow down evolution of new variants
- making the new therapeutics accessible to everyone
- and helping to counteract the infodemic with clear communication of the best available science.
In this way we can end the death and tragedy and the global health emergency.
We need to step this up and rapidly vaccinate the world and together we can end the emergency and slow down and stop the emergence of these new variants.
NOTE To read short version of this article, skip through section titles - then drill down into any that interest you - I provide "skip to next section" links to make this easy to do and the titles summarize the sections, a bit like mini abstracts for each section.
Total length = just short of 15,000 words, or about 50 minutes to read it all at 300 wpm.
IF OMICRON IS MILDER, IT COULD GET MORE SEVERE AGAIN - UNLIKE A MODERN VACCINE DESIGNED TO STAY MILD LIKE CODAGENIX
Sabin's live attenuated polio vaccine is a milder version of a serious disease but in the 1950s they didn't have the knowledge we have to day about how to prevent a mild variant reverting to severe - and 1 in 750 000 doses reverts to severe. When that happens the severe polio spreads as a new outbreak.
As with Sabin's live mild attenuated vaccine, the same could happen with COVID once nearly everyone has had Omicron - a new variant arises that evades the immunity from Omicron in the landscape opened up by these new mutations - and our science is not yet at the level where we can predict what it would be like after further evolution.
Some experts have suggested eventually COVID will evolve to become mild - but the evidence for this is weak.
In this article I look closely at two landmark papers coming to opposite conclusions. So far in the evolution from ancestral to alpha to Delta the direction has been towards more severe.
Omicron seems to reverse this, on early indications. However it may have spent a year in an animal host, perhaps rodents. That might have attenuated it and coming back to humans, might it evolve to more severe again like Sabin's vaccine, which likewise was attenuated through passage through animals?
Note - this is my own reasoning that
1. Sabin's attenuated polio was attenuated through passing through rodents and reverts sometimes
2. One of the leading hypotheses is that Omicron spent a year evolving in rodents.
3. Maybe Omicron was attenuated in rodents too and could revert?
I've not seen any of the experts make this particular argument yet. Do say if you know a source. The rest of this blog post, that we don't know how COVID could evolve, and it could evolve to be more severe is just expounding on the papers and statements by experts.
However it IS possible to have a mild variant that's engineered to STAY mild. Codagenix does that and may soon add to our impressive quiver of vaccines we have already - it's also a nasal spray to help with fear of needles and likely to be especially effective at stopping transmission. There are many others on their way.
With a good enough vaccine it's not impossible it becomes another eliminable disease, like yellow fever, which also has animal reservoirs but with an excellent vaccine, it is classified as eliminable as a public health problem for humans (Skip to: Diseases that can be eliminated in humans).
We are getting there. The vaccines are gradually reaching the world. Here for instance is a story from Gavi, the vaccine alliance, about how vaccines are helping nomads get back to normal on the Mongolian steppes
Nomads in lockdown - COVAX reaches the Mongolian steppes
Image from: Rider in Mongolia, 2012
(used a different image from the one Gavi use for copyright reasons)Nomads in lockdown: COVAX reaches the Mongolian steppes
I wrote this blog post to counter articles and tweets saying that milder COVID is a "blessing" and that we should let it spread. Many are sharing this misinformation.
Such as this one:
- Covid silver lining: ‘Extremely mild’ Omicron variant is rapidly killing off much more deadly Delta coronavirus mutation
A milder Omicron is at most a temporary respite for a few weeks and may not even be that as we don't know it is milder yet, and even if it is a little milder in some age groups such fast surges can still overwhelm health systems such as ICU beds. UK's Omicron seems to be doubling in < 3 days (see tweet) and look how fast it's rising in SA (see tweet)
We can do this, we can fight Omicron, we can end the death and tragedy with vaccines and masks and #DOITALL, but we all need to work together to break transmission. Just letting it spread is not a wise strategy as it is not a vaccine and is no substitute for vaccination.
NEW LANDSCAPE OF POSSIBILITIES TO MUTATE INTO - FOR OMICRON WE CAN'T PREDICT BUT WE CAN ENGINEER A MILD LIVE VACCINE TO BE SAFE
Omicron’s 50+ mutations gives the virus a jump pad to evolve into a new landscape of possibilities. We can't predict what this means for new variants after Omicron or direct how it evolves.
Vaccines and #DOITALL are a safe way out of this. Experts think vaccines we have already will still protect against severe disease and Pfizer, Moderna and Novavax are all working on new versions of their vaccines tweaked to Omicron that can be ready early 2021.
Dr Swaminathan: "We still need to find out if there is any loss of protection but we think vaccines will still protect against severe disease as they have against the other variants."
But Omicron is not a vaccine, and letting mild variants of COVID spread without trying to stop them is NOT a safe way to try to end the pandemic and the global public health emergency.
It is however possible to DESIGN a mild variant of COVID to be safe and use that as a vaccine to add to our already impressive list - CODAGENIX's live attenuated COVID vaccine is already in phase 2 with promising results. In the decades since Sabin made his vaccine by passing polio through numerous animal hosts we have learnt how to prevent an attenuated vaccine from evolving back to severe like his one did.
We have amazing vaccines far better than any flu vaccine has ever been. Most viruses never evade vaccines - there has been no vaccine escape for the MMR vaccine developed in 1971. Even Salk's polio vaccine developed in 1954 had no vaccine escape, and the changes were mainly to do with how to manufacture it (skip to: Why most viruses find it so hard to evade vaccines)
COVID has some vaccine evasion but it's between measles and flu, and nowhere near the level of flu. Some of our new second and third generation vaccines like Gritstone bio are engineered to be very hard to escape.
We likely need boosters every year or so - but some of the vaccines like Codagenix may last longer than that (skip to: Codagenix's COVAVAX may be a safe live attenuated COVID vaccine) - and we most likely can boost with the same vaccine over and over, especially if we can reduce transmission and get COVID numbers low again, and keep them low (Skip to: To stop more variants is quite simple - less transmission - less variants)
EVEN IF OMICRON WAS EXTREMELY MILD FOR EVERYONE - IT WOULD NOT BE SAFE TO LET IT SPREAD UNCHECKED - BUT CODAGENIX HAVE DESIGNED A SAFE MILD VARIANT CURRENTLY IN TRIALS AS A VACCINE
Even if we knew that Omicron was currently extremely mild for everyone (which it isn't), letting Omicron spread unchecked wouldn't be a safe strategy long term. Dr Tedros of the WHO put it like this in his opening remarks at the special session of the World Health Assembly on 29th November 2021
The longer vaccine inequity persists, the more opportunity this virus has to spread and evolve in ways we cannot predict nor prevent.
Take the example of Sabin’s live attenuated polio vaccine in the early days of vaccine development (from the 1950s). Sabin made polio milder by passing it through animals over and over so that it adapted better to animals than to humans. This was meant as a low cost alternative to Salk's more expensive inactivated vaccine (killed using formalin).
Sabin's milder variant of Polio was believed to be safe to use as a vaccine at the time - but researchers later found that once in every 750 000 doses it reverted to a serious disease.
In a similar way any of those 50+ code changes that lead from Ancestral to Omicron can easily change again, to a disease with the same severity of Delta, or evolve further in ways we can't predict. We don't know what all those changes have opened up for the virus by way of future evolution.
With modern science it is possible to DESIGN a safe milder variant of a deadly virus. These are called "live attenuated vaccines" and if we can do this we can add to our already impressive toolkit of vaccines to help stop COVID.
The measles vaccine is an example of a long established safe live attenuated vaccine. We also now have a safe live attenuated polio vaccine authorized for emergency use to replace Sabin's vaccine.
Codagenix have developed a promising milder version of COVID as a vaccine called COVI-VAC. Their engineered very mild variant is now in phase 2 and may move to phase 3 soon and could be a game changer if it succeeds.
So there is nothing wrong with the idea of a milder variant stopping a more deadly variant - so long as you know for sure it won't revert to deadly. The problem with a milder wild variant is that it's only accidentally mild, through random evolution. When we don't understand why or how it got milder, how can we know where it will evolve next? So far, up to Delta, COVID evolved in the direction of more virulence, if anything.
I'll go into this in more detail in this article in the sections starting:A wild milder variant is an unknown quantity- scientists argue both ways about future evolution of COVID in two landmark papers
Also Omicron is nowhere near as mild as a live attenuated vaccine. We don't even KNOW Omicron is milder yet.
Preliminary data suggests it might be milder for some age groups - anecdotally they see less need of oxygen, fewer in ICU, shorter stays in hospital, but it's early days yet, and they say it is FAR too soon to analyse data properly. See:
Also even if it is milder, the ICU cases can overwhelm the health system especially with how fast it is increasing in South Africa
This, along with the now >24% test positivity in South Africa and nearly 5-fold rise in cases in a week certainly (>16,000 cases today) are all concerning https://t.co/EwTOC6nHgW— Eric Topol (@EricTopol) December 3, 2021
Different versions of this graph showing 7-day rolling avg #COVID19 cases in Gauteng floating around. For those interested, here's the latest update tonight:— Ridhwaan Suliman (@rid1tweets) December 5, 2021
Will share an analysis, including a look at hospitals and deaths, as soon as I get a chance..#Omicron #Gauteng #4thWave pic.twitter.com/w2VWcsmLkl
Before I get to the details just to reassure you that we are not back to square 1. All the same public health measures still work and vaccines are sure to still be very effective though some of the changes may let it evade part of the immune response (both natural and vaccine induced)
What you need to do
- Get the vaccine when offered it
- #DOITALL - there are many things you can do short of a lockdown to protect yourself and others around you from COVID
We need to continue to do that no matter how mild or otherwise Omicron might turn out to be when they are able to analyse the data in a few days time.
EARLY REPORTS OF “EXTREMELY MILD” CASES - FLAGGED BY THE DOCTOR WHO REPORTED THE VARIANT AS UNUSUALLY MILD COMPARED TO DELTA
Skip to: Many Delta cases are mild too
We are getting early reports that Omicron may be very mild. It is far too early to say that it is indeed a milder variant. Many Delta cases are also very mild, especially in younger people.
Even with the very elderly most people get Delta very mild or it may be asymptomatic. With perhaps 80% of cases very mild, depending on the age group, It’s easy to get a cluster of mild cases of any COVID variant.
A milder wild COVID variant may give short term relief to health systems but can REVERT like Sabin's attenuated polio vaccine or evolve in ways we can't predict
The safe way out is to use vaccines & #DOITALL
However we CAN DESIGN mild variants to be safe to use as a vaccine like Codagenix's COVI-VAC
The doctor who alerted the world to the first Omicron cases noticed it because she saw cases that were unusually mild for Delta. So that’s encouraging.
It’s extremely mild
What we are seeing clinically in South Africa - and remember I'm at the epicenter, that's where I'm practicing - is extremely mild. We haven't admitted anyone. I spoke to other colleagues of mine. The same picture.
One doctor’s experience - note Delta also has many mild cases - detailed analysis takes days to weeks
Her observations are suggestive not conclusive.
I go into this some more with a complete transcript of her interview and paraphrase to help mildly autistic readers here:
. Omicron is very transmissible - but many cases are mild - hopeful it’s no more serious than Delta - and vaccines expected to remain very effective - WHO say to continue to #DOITALL as much as you can
HOWEVER MANY DELTA CASES ARE MILD TOO AND THERE ARE ALSO MANY HOSPITALIZATIONS THAT MAY BE OMICRON - AND WHO WARN THAT ALL VARIANTS CAN CAUSE SEVERE DISEASE OR DEATH - PREVENTION IS KEY
Also though many Omicron cases are mild, there are hospitalizations too including a surge in hospitalization of infants age 0–2 (as also happened with Delta in South Africa). This doesn't mean it is worse than Delta but shows it is not as mild as a cold,
The WHO warn:
There is currently no information to suggest that symptoms associated with Omicron are different from those from other variants. Initial reported infections were among university students—younger individuals who tend to have more mild disease—but understanding the level of severity of the Omicron variant will take days to several weeks.
All variants of COVID-19, including the Delta variant that is dominant worldwide, can cause severe disease or death, in particular for the most vulnerable people, and thus prevention is always key. [Emphasis mine] . Update on Omicron
“BLESSING IN DISGUISE” IS ABOUT SHORT TERM IMPACT OVER THE NEXT FEW WEEEKS, “EVOLVE IN WAYS WE CAN’T PREDICT” IS ABOUT LONGER TERM EVOLUTION TO MORE VARIANTS
The “blessing in disguise”.quote is from a video by the virologist Chris Smith in a TV interview but it is being taken to mean much more than he actually says.
If this new variant turns out to displace delta it causes delta to shuffle off and it gets replaced by this new variant but this new variant is much more mild in clinical presentation actually it could be a blessing in disguise some are saying because you end up with something circulating that pushes out the nasty stuff but is much more trivial to catch
If Omicron is milder it may help in the short term, and that’s all he is saying there.
Experts in the UK are concerned about the pressure on the NHS over winter and on those timescales a milder variant may help. Also he didn’t give it as his professional opinion he just said a blessing in disguise some are saying
Whether or not it helps a little relieve pressure on the NHS and other health systems in the very short term of the next few weeks, we can’t predict how it will evolve next.
Dr Tedros of the WHO takes a longer term and global perspective in his opening remarks at the special session of the World Health Assembly on 29th November 2021
The emergence of the highly-mutated Omicron variant underlines just how perilous and precarious our situation is. …
The longer vaccine inequity persists, the more opportunity this virus has to spread and evolve in ways we cannot predict nor prevent.
I’d like to elaborate here on his
“evolve in ways we cannot predict or prevent”.
From the news stories about that “blessing in disguise” remark and from things people say on social media - it’s clear that many people don’t know the background, why it is that we can’t predict or prevent the evolution of the virus.
Dr Mike talks about this at 40 minutes into the video.
Maria's point is exceptionally, exceptionally important in terms of the overburdening of the health system and that severity profile. If we allow a mild disease to transmit unchecked it will generate huge pressure in the health system which will decrease the positive outcomes for people and that's what we've seen with many before.
There is an assumption out there that as a disease becomes more transmissible it will become milder. I would hope that most viruses would become less transmissible and milder, that would be the ideal outcome.
There is an assumption here that as a disease becomes more transmissible it will become milder
But I think there's a little bit of an urban legend around that process. That doesn't necessarily happen.
Allowing a mild disease to transmit unchecked will generate huge pressure on the health system.
That decreases positive outcomes for everyone
It's also something, I think, we need to caution everyone on. There is an assumption out there that as a disease becomes more transmissible it will become milder. I would hope that most viruses would become less transmissible and milder, that would be the ideal outcome.
There is an assumption here that as a disease becomes more transmissible it will become milder
But I think there's a little bit of an urban legend around that process. That doesn't necessarily happen. There is pressure on the virus to adapt and become more transmissible because that's an evolutionary pressure.
This is a bit of an urban legend. It doesn't necessarily happen.
There is evolutionary pressure on a virus to adapt and become more transmissible
The outcome of whether a virus is more or less severe is much more random. It can happen, it can not happen and in that sense that's why we don't know and I think we have to be very, very careful in making any absolute determinations.
Whether a virus is more or less severe is much more random - can happen and can not happen. That's why we don't know [what COVID will do]
Remember in this that much of the severe outcomes, much of the hospitalisation, much of the death is not mediated by the virus, it's mediated by our own immune systems and our response to the presence of the virus.
So in a sense some of the most negative outcomes here are more to do with underlying conditions - diabetes, hypertension - and other factors that make the course of the illness more severe for a certain group of individuals.
Much of the severe outcomes, hospitalization and death is not mediated by the virus [not directly involved, the virus is gone from the body by then].
Severe outcomes are mediated by our immune systems and our response
Therefore they're locked into the system in a sense so therefore I don't expect in general viruses to become milder. It can happen randomly but it's not a direction that as a disease becomes more transmissible it becomes milder. I think we should have hope and everyone should have hope and we should hope for the best outcome but in this particular case hope is not a strategy and we need to be very, very careful on making any final determinations on severity.
So I don't expect in general viruses to become milder. It can happen randomly. But it's not a direction that as a disease becomes more transmissible it becomes milder.
We should hope for the best but hope is not a strategy. We need to be very very careful about making a final determination about severity
EXAMPLE OF SABIN’S VACCINE WHICH REVERTED TO SEVERE IN ONE DOSE PER 750,000 FOR FIRST DOSES AND ONE DOSE IN 6.9 MILLION FOR REPEAT DOSES
A milder wild variant of COVID is NOT SAFE.
Sabin developed a mild version of polio by repeatedly passing it through animals and cell cultures. It can spread from person to person and did indeed wipe out the more serious wild polio - but it can sometimes revert to the severe disease. This is very rare, estimated at between one case per 750 000 doses and one case per 6.9 million subsequent doses.
But that was enough to be a serious problem once millions were vaccinated. It is the main reason that polio has not yet been eliminated from the world. The stronger economies were able to transition to the inactivated whole vaccine as cases went down and polio is now eliminated from the Americas. But other countries, especially Africa, were not able to afford the inactivated Salk’s vaccine, so they vaccinate with Sabin’s vaccine and then get small outbreaks from time to time when the vaccine reverts to the severe disease.
IF OMICRON IS MILDER IT MIGHT HAVE HAPPENED IN THE SAME WAY AS FOR SABIN'S VACCINE - OUT OF SEVERAL POSSIBILITIES - SOME EXPERTS THINK IT MAY HAVE SPENT THE LAST YEAR IN AN ANIMAL HOST
Stat Times put it like this:
The theory goes that some type of animal, potentially rodents, was infected with the SARS-CoV-2 virus sometime in mid-2020. In this new species, the virus evolved, accumulating roughly 50 mutations on the spike protein before spilling back over into people.
Kristian Anderson,, immunologist at SCRIPPS institute is one of those who slightly favour this hypothesis
“I know that most people think that these [come from] immunocompromised individuals, and I do think that that’s plausible, but to be perfectly honest, I actually think this reverse zoonosis followed by new zoonosis seems more likely to me given just the available evidence of the really deep branch, and then the mutations themselves, because some of them are quite unusual,” Andersen told STAT.
“I don’t think we should dismiss that possibility, because I think it’s definitely on the table.”
I slightly favor reverse zoonosis for a few reasons:
1. The lineage is old and undetected circulation in immunocompromised patient(s) for this long seems unlikely
2. SARS-CoV-2 is a generalist virus and we have seen human>animal>human transmission happen in e.g., mink
3. Several of the mutations in Omicron have been observed in animals, including rodents:
Other possibilities include that it spent the last year in a single immunocompromised patient - and that it evolved in some isolated human population with limited connection to the rest of the world and low levels of sequencing.
We now have a solution for Polio, there is a new more stable live attenuated vaccine. nOPV2 which recently got emergency approval from the WHO which is much less likely to revert to the severe form.
It got emergency use listing in November 2020
WE COULD GET EXTREMELY MILD VARIANTS OF COVID ALONGSIDE SEVERE VARIANTS - EXAMPLE OF THE MUCH MILDER ALASTRIM STRAIN OF SMALLPOX
A mild and a severe variant of COVID could co-exist. There were two strains of smallpox before it was eradicated. Variola major is the one everyone knows about, with a 30% fatality rate. But with a PCR test it was possible to distinguish Variola minor, also known as Alastrim which had a case fatality rate of only 1%. It was the dominant form of the disease in the United States, South Africa and Great Britain.
Alastrim did help to reduce the fatality of smallpox in the countries where it spread.
According to a tweet thread by Trevor Bedord, we could also have a wave of Omicron followed by a delta wave then both co-existing with either dominant in the long term - this is one possibility.
Assuming Delta R0 is 6, with lower intrinsic transmissibility and higher immune escape (Omicron R0 = 4, immune escape = 66%), Omicron has initial Rt of 2 and undergoes a large wave. However, this wave has relatively little impact on Delta. 7/15 pic.twitter.com/mTTjswXDkU— Trevor Bedford (@trvrb) December 13, 2021
Or we could have a big wave of Omicron which then is made extinct by Delta.
In fact, we can plot out parameter combinations that result in scenario 1 (extinction of Delta, yellow), scenario 2 (co-circulation of Delta and Omicron, light gray) and scenario 3 (extinction of Omicron after epidemic wave, dark gray). 10/15 pic.twitter.com/r64gNufqQf— Trevor Bedford (@trvrb) December 13, 2021
So there are many possible future trajectories.
Even if Omicron, or some future variant, was much milder than Delta (not known) we have no idea where evolution takes it next,
Yes it could be like Alastrim and stay mild, but it could be like Sabin's attenuated polio vaccine, and indeed like the way COVID has evolved so far through ancestral, alpha and delta and evolve to be more serious if anything.
We need to slow down evolution of the virus by vaccination and public health, not encourage it.
A NEW VARIANT COULD ALSO GET MILDER FOR SOME CONDITIONS OR AGE GROUPS AND YET BE MORE SEVERE FOR OTHERS
Skip to: Everyone agrees - get vaccinated
Also it doesn’t need to be milder for all age groups even if it is milder for some people
E.g. Omicron could be milder than Delta for some age groups and more serious for others, milder for young adults, say, but more serious for elderly or kids or infants.
This is something that may be happening in South Africa.
The omicron variant is sending more children to hospital in South Africa. Infants, who largely only had a mild course of illness with previous variants are now experiencing moderate to severe symptoms.— Dr Zoë Hyde (@DrZoeHyde) December 5, 2021
H/T: @KatePri35772611 & @NjbBari3.pic.twitter.com/DmdM47dGts
Full video here
ONE THING EVERYONE AGREES ON - GET VACCINATED - THIS IS BOUND TO REDUCE THE RISK OF SEVERE DISEASE AND DEATH
Before I continue first reminder - do get vaccinated. The one thing the experts are sure of is that the vaccines are bound to reduce your risk of severe disease and death.
The WHO say that because of multiple spike mutations - there is a high likelihood of :immune escape from antibodies - but the cell-mediated immunity is harder to predict (killer T cells and anything else not involving the antibodies). They expect data in the next few weeks. They continue:
Despite uncertainties, it is reasonable to assume that currently available vaccines offer some
protection against severe disease and death.
The sooner you get your vaccine the better. If you haven’t had your first shot, now is the time to get it (if available).
Especially after two doses your risk is greatly reduced and then if you are offered a booster be sure to get that too as they have been very effective against Delta, far more than expected.
Most #COVID19 vaccines elicit broad enough immune responses to have some protection against severe disease by different #variants. Let’s wait for the data rather than speculating about the efficacy of existing vaccines @WHO @GaviSeth @CEPIvaccines @UNICEF @AfricaCDC @Chikwe_I https://t.co/ra9rVKOQSe— Soumya Swaminathan (@doctorsoumya) November 30, 2021
Codagenix is a live attenuated version with hundreds of changes that are almost impossible to revert. It has passed phase 1 which was done in a secure quarantine facility in London to prevent it from escaping into the wild on the remote chance it turned up any problems.
Phase 1 was a success. It seems to block viral replication in the nose before the virus can get to the lungs which is very promising.
"Our vaccine candidate appears able to block surrogate SARS-CoV-2 replication in the nose before it reaches the lower airways or lungs. This is likely achieved by stimulating both a systemic and mucosal immune response, highlighting the value of an intranasal, live-attenuated vaccine model.”
COVI-VAC is now in a larger scale phase II trial with 6000 healthy volunteers - and if all works well then it can proceed to larger phase III trials.
It’s a nasal spay, can be stored at room temperature and doesn’t need medical professionals to administer it. Dr Rob Coleman says they find it is efficacious against newly emerging variants and has potential for a longer lasting immune response.
“In addition, we have generated data recently in preclinical models showing the vaccine is efficacious against newly emerging variants. We’re hoping it can provide a much broader immune response.”
They did the phase 1 trial through hVIVO who are gearing up to do human challenge trials.
Eventually hVIVO will be challenging healthy volunteers with COVID virus after vaccinating them with some of the best candidates for COVID vaccines - a very fast way of approving the vaccines.
They are paid £3,500 (€3,900) for their time, a rate set by a UK ethics panel. “Quite a few are journalists writing books or people finishing theses. Anything that needs two weeks’ peace and quiet.”
But for this trial then hVIVO just tested the lave attenuated COVI-VAC in a phase 1 trial - their volunteers received the live attenuated virus, not the COVID virus - but their facilities was what’s needed for such a test.
TECHY DETAILS - COVI-VAC WORKS BY SLOWING DOWN THE REPLICATION OF THE VIRUS TO A METAPHORICAL SNAIL’S PACE
The way it works is that they introduced 283 carefully designed mutations into the virus. These mutations produce the same proteins as the wild virus, so the mutated virus looks the same to the immune system, all the same antigens to latch ont.
However the mutated code is designed to be harder for the virus to replicate and to produces less of the proteins the virus needs.
They also remove a site called the furin cleavage site. This is a section of the spike protein that gets snipped just before the virus leaves the cell - which then reshapes the spike to be more infectious, better able to infect other cells. Removing this short section of the virus makes it less able to infect other cells.
Their plan is to slow down the virus so it does everything at a snail’s pace (metaphorically) so that it easier for the body to overcome.
Techy details here
More precisely - this is possible because each amino acid in a protein is coded for by a “codon” of three letters in the gene sequence. But each amino acid can be be coded for by more than one gene sequence. So you can substitute one three letter gene sequence (codon) for another without changing the protein that it makes.
What they do is to make these substitutions in a way that increases the number of times that G follows C in the RNA code (CpG) and the number of times A follows U (UpA).
Why this works is unknown. But RNA viruses avoid those two-letter combinations in the code. Researchers have found that if they artificially increase the number of times these two letter combinations occur in the code, RNA viruses replicate much more slowly.
Then on the safety - they can’t test it with millions of people but they have designed it with so many mutations, 283 of them, it’s too many for the virus to be able to revert to the severe disease. In tests they find that each of these mutations are very stable.
COVI-VACA inhalable and immunity might last longer, for 5 years from this interview from 2020.
UNLIKE COVI-VAC - A WILD EVOLVED MILD VARIANT IS AN UNKNOWN QUANTITY - SCIENTISTS ARGUE BOTH WAYS ABOUT WHICH WAY COVID WILL EVOLVE - IN TWO LANDMARK PAPERS
The design for COVI-VAC shows that if we have a well designed live attenuated virus - then yes - that can protect us. We may have such a vaccine if Codagenix is approved.
However it’s not safe to rely on a wild evolved weak variant to remain mild.
There are two main papers on this topic. One that says COVID could eventually evolve to be mild like a common cold:
Another criticizes that theory, says that so far it has evolved in the direction of more virulence if anything, and says it could go either way.
In both cases we see from Delta that it’s certainly possible for variants to become more serious at least temporarily whatever the end state of the evolution is. Delta causes more hospitalization though not more deaths.
A report this summer, published in The Lancet Infectious Diseases, found that people in England with Delta had double the hospitalization risk of those with Alpha, which was previously the dominant mutation in that country.
WHY COVID COULD POTENTIALLY BECOME MORE DEADLY AS IT GETS MORE TRANSMISSIBLE - THE DEATHS HAPPEN LONG AFTER A COVID PATIENT INFECTS OTHERS
Skip to: Smallpox never got milder
Evolutionary pressure is to become more infectious. But deaths happen long after infectiousness is over.
Adapted fom Figure 2 from Avirulence theory, immunity and trade‐offs
So there isn't any downside to the virus if increases in infectiousness kills the patient long after the patient can pass the infection on to anyone.
There is no advantage to the virus to kill the patient. It is rather that it might be an accidental side effect of whatever changes make the virus more transmissible that the patient eventually dies.
This depends on the virus. For some viruses it might be a downside but for COVID it’s infectious so early on long before the patient is really sick.
The patients become sick and may eventually die not because of the virus but because of the damage it caused and other long term effects such as the immune system responding to the damage the virus caused. By then in most patients, the virus is long gone.
This delayed effect insulates the virus from the effects of what it does to the patient.
The paper critical of the avirulence theory gives the example of HIV - the most virulent strains are also most transmissible.
Since the early 1980s, an explanation for the maintenance of virulence is that the latter can be correlated with traits that are adaptive for the parasite. For instance, as shown in the case of HIV, strains that cause the most virulent infections tend to be the more transmissible, and the correlation between the two traits could be mediated by the virus load
There is some signs that the same is true of SARS-CoV2.
In the case of SARS- CoV- 2, some (limited) evidence suggests that increased virulence can be associated with variations in other life-history traits that are adaptive for the virus. For instance, a contact-tracing study showed that individuals with higher viral loads tend to infect a larger proportion of their contacts.
Individuals with higher viral loads tend to infect more contacts
Furthermore, longitudinal follow- ups show that patients who develop more severe infections tend to have higher virus loads (estimated via the cycle threshold values of RT- qPCR tests) for a longer time. Therefore, it could be envisaged that an increased virus load could lead to both increased virulence and contagiousness. Finally, there are data suggesting that the variant is causing longer infections
Patients who develop more severe infections tend to have higher viral loads - and for a longer time. The alpha variant may be causing longer infections
This next section is by way of background information, not in the paper.
There are many examples of deadly diseases that never got milder.
Smallpox killed 30% of those infected.
There are four main clinical forms of smallpox, each with different characteristics. During the smallpox era, the case-fatality rate differed for the different clinical forms, but it was approximately 30% overall in unvaccinated individuals.
Though as we've seen, Smallpox co-existed with a milder variant, variola minor, or Alastrim which took over in some countries the original Variola major never got milder. That's a disease that co-evolved with humans for thousands of years, without becoming significantly less severe. Egyptian mummies had smallpox-like rashes on them, so it's probably been in humans at least since then
The origin of smallpox is unknown. The finding of smallpox-like rashes on Egyptian mummies suggests that smallpox has existed for at least 3,000 years. The earliest written description of a disease like smallpox appeared in China in the 4th century CE (Common Era). Early written descriptions also appeared in India in the 7th century and in Asia Minor in the 10th century.
LOW CONFIDENCE EVIDENCE THAT COVID MAY GET MILDER - FOUR MILD CORONAVIRUS COLDS - BUT ONE WAS PROBABLY ALWAYS MILD, ONE UNCERTAIN, AND TWO MORE FROM A COMMON ANCESTOR AROUND 1100 OF UNKNOWN SEVERITY
The main reasoning for the idea that COVID will get milder is based on our four coronavirus colds being mild and the new ones SARS, MERS and COVID all severe.
At first sight that may seem impressive statistics. But it’s less compelling when you get into the details.
- HKU1 was probably always mild - it crossed over to human in the 1950s. But there was no severe pandemic at that time and our medical records in the 1950s were already good enough so we couldn’t have missed even a minor pandemic.
- NL63 and 229E probably derive from common ancestor of unknown severity around 1100, so that doesn't tell us much. That leaves
- OC43 is the only remaining virus that may have got mild quickly - so it really depends on whether you think the 1889 pandemic was OC43 - evidence of flu antibodies in old survivors suggest it was flu.
These details are from
It could be OC43 is very weak. So the case for coronavirus colds evolving rapidly from more severe variants is very weak.
Meanwhile there is nothing we know about evolutionary pressures to suggest it will go mild. We can’t really predict what will happen from first principles if I understand right.
So, basically the case hangs on OC43. And then if they are right about OC43 then a generalization that whatever factors lead to OC43 getting mild in a few years will also work for COVID.
It is impossible to say if the 1889 pandemic was OC43 because there are no samples of the virus. The only evidence is based on
1. symptoms slightly unusual for flu could be OC43
2. antibodies for flu found however.
Scientists argue both ways.
If OC43 which originated in pigs in the late 1880s was always mild then that leaves zero evidence to suggest COVID will evolve to be mild.
So the best strategy remains to keep transmission low, solve problems with vaccine inequity and the infodemic and if it is a mild variant, great but it doesn't mean we should make it easier for the virus to continue to evolve as we don't know where it goes next.
SO IS IT LIKELY TO GET MILDER AS IT EVOLVES? EXPERT OPINION VARIES - DEPENDING ON THEIR INTERPRETATION OF A PANDEMIC IN 1889
OCO43 which is a common cold just possibly might have been a severe disease in the late 1880s - that's when it jumped to humans from pigs and there was a big outbreak of what they thought was flu but just possibly might be OC43,if so it evolved to be mild in just a few years. This is my graphic summary of the evidence:
That's the optimistic view on coronavirus evolution. Others are skeptical about that argument and says it proves nothing.
They say that HKU1 seems to have always been mild - it jumped to humans around the 1950s and there is no sign of a serious pandemic when it was supposed to jump over to humans from rodents. See figure 1 from Molecular Evolution of Human Coronavirus Genomes
The critics in that second paper say that we would have noticed a pandemic of a severe coronavirus like COVID back in the 1950s. There were fewer old people back then, but even so, a pandemic similar to COVID in the USA and France would have killed 3 in 1000. We’d have noticed a case fatality rate like that as a novel pandemic even with our science of the early 1950s.
This is their back projection of the case fatality rate for COVID, based on the age pyramid at the time back to the 1950s:
Figure 2 from Avirulence theory, immunity and trade‐offs
So - HKU1 likely was never as serious as COVID.
WAS THE 1889 PANDEMIC OC43? SURVIVORS HAD ANTIBODIES TO H2N2 FLU BUT NOT TESTED FOR OC43 - AND SYMPTOMS ARE INCONCLUSIVE
Some think the pandemic of the Russian Flu in 1889 was OC43 but the evidence is weak.
It could be just another of our many flu pandemics. Elderly people who were alive at the time were found to have H2N2 antibodies in their blood in an analysis done using samples collected before the 1957 H2N2 epidemic in the Netherlands.
However, postepidemic analysis in 1957 of the influenza antibody pattern in sera of people who were 50 to 100 years old indicated that H2N2 influenza antibodies might have originated from the 1889-1890 pandemic
The paper they refer to is here: Pre- Epidemic Antibody against 1957, Strain of Asiatic Influenza in Serum of Older People living in the Netherlands.
“However, it is tempting to speculate about an alternative hypothesis, that the 1889-1890 pandemic may have been the result of interspecies transmission of bovine coronaviruses to humans, resulting in the subsequent emergence of HCoV-OC43.
Another argument is the fact that central nervous system symptoms were more pronounced during the 1889-1890 epidemic than in other influenza outbreaks. It has been shown that HCoV-OC43 has neurotropism and can be neuroinvasive
However influenza outbreaks do often cause central nervous system symptoms too, especially in pandemics when they have first jumped to humans before the virus adapts.
Influenza viruses can be divided in seasonal and pandemic. The seasonal influenza A viruses (H3N2 and H1N1) cause yearly epidemics, while pandemics of influenza are the consequence of cross-species transmission, followed by adaption to humans . The CNS [Central Nervous System] is the most common site of extra-respiratory complication of influenza infections
They go on to give a long list of central nervous system complications for influenza pandemics
- Febrile seizures and encephalopathy (mainly kids)
- increased frequency of ischaemic stroke
- late post viral syndromes involving the nervous system such as GBS, cerebellitis, Kleine-Levin syndrome, myositis and transverse myelitis
So, this seems quite a weak argument, especially given the number of influenza pandemics we have.
FLU TYPICALLY BECOMES LESS VIRULENT EVERY TIME IT JUMPS TO HUMANS - BUT COVID IS NOT A STRAIN OF FLU - GAVI REMARKS THAT UNLIKE THE ENCOURAGING FLU EXAMPLES - COVID EVOLVED TO BE MORE SEVERE FROM ANCESTRAL TO DELTA
OC43 is the only example anyone has suggested that MAY be a case of a coronavirus rapidly becoming less serious.
Flu indeed does lose virulence when it jumps to humans. But polio, smallpox, measles, don't change virulence after decades of evolution.
It could go any way
Gavi, the international alliance for distributing vaccines globally, summarizes it like this:
There are historic examples of viruses which gradually became less dangerous over time, such as the H1N1 influenza viruses responsible for the 1918 “Spanish flu” and 2009 “swine flu” pandemics, and the myxoma virus that causes myxomatosis in rabbits.
They also talk about the OC43 virus
OC43, a human coronavirus that causes the common cold, is also believed to have started out as a more deadly coronavirus; it may have been responsible for a pandemic that began in 1890, which killed more than a million people worldwide.
However they say the evidence so far for COVID is the opposite, alpha seems to have got more deadly than ancestral, perhaps as much as 64% more deadly and delta seems to be more likely to result in hospitalization
If we’re lucky, SARS-CoV-2 may go the same way. However, the evidence to date is somewhat dispiriting. One study estimated that the death rate associated with the highly transmissible Alpha variant, which was first detected in Kent, England, in December, was up to 64% higher, compared to previous variants. And, although it’s still too early to say whether the Delta variant is more deadly, it appears to be both more transmissible and more likely to result in hospitalisation if you’re infected with it, compared to the Alpha variant.
Then they explain how a respiratory virus doesn’t necessarily need people to be sick to spread.
The trouble is that how easily a virus transmits from one host to another doesn’t necessarily correlate with how sick it makes its host. Take the bacterium that causes cholera for example, which needs people to get sick – often deadly sick – before it can spread, principally through diarrhea. Respiratory viruses need people to be close enough to be breathing the same air, to be transmitted to a new host, but don’t necessarily need them to be sick. SARS-CoV-2 is thought to be most infectious shortly before and during the first few days after people develop symptoms.
As I explained, then by the time the most severe symptoms develop, the virus is typically long gone
The most severe COVID-19 symptoms don’t tend to develop until the second week of the infection, by which time most of the active virus has been neutralized by the body’s immune response. Indeed, the catastrophic organ failure and breathing difficulties experienced by people with severe COVID-19, are largely driven by an overactive immune response to the virus, rather than by the virus attempting to transmit itself to a new host.
It’s only if the virus causes people to self-isolate before they transmit the virus to others that there is a downside of the severity for the virus
So, unless SARS-CoV-2 becomes so virulent that it causes people to become severely ill and self-isolate before they transmit the virus to other people, there is no pressure on it to become less deadly.
SUMMARY OF KNOWN CORONAVIRUSES IN HUMANS - 3 NEW SERIOUS CORONAVIRUSES, 1 PREEXISTING LIKELY ALWAYS MILD, AND 2 NOW MILD OF UNKNOWN ORIGINAL SEVERITY
- SARS, MERS, COVID, all new and serious
- HKU1 likely originally mild, crossed over 1950s
- OC43 may have got mild in a few years in 1889, may be always mild
- NL63 and 229E - single ancestor in 1100 unknown severity
When you break it up like that the evidence isn't compelling. It’s striking that all the newest variants are severe.
But it’s not impossible that OC43 was also initially mild given that HKU1 was. As for the common ancestor of NL63 and 229E it really makes little difference on the timescale of a century whether the common ancestor was severe or mild. We need to know what happens on timescales of years not centuries.
COVID IS MUTATING TO INFECT THE UPPER RESPIRATORY TRACT BETTER LIKE COLDS - BUT SO FAR CONTINUES TO INFECT THE LOWER RESPIRATORY TRACT TOO
One way COVID could get milder is by infecting the upper respiratory track. That has advantages for the virus as the immune system is weaker there, with a stronger immune response in the lungs.
If the virus specializes in the upper respiratory tract, it would also lead to a milder disease.
However the paper critical of the avirulence theory gives the example of the D614G variant of COVID. It got better at reproducing in the upper respiratory tract, but this didn’t reduce its ability to infect the lower respiratory tract as well.
So far with COVID there
- does seem to be some evolutionary pressure to infect the upper respiratory tract but
- no sign yet of pressure to stop infecting the lower respiratory tract.
Also there are signs of
- some pressure to evade the upper respiratory tract to avoid detection.
One variant of interest seemed to be avoiding the upper respiratory tract - it may be favoured because this lets it evade detection in nasal swabs.
COVID could get milder by specializing in infecting upper respiratory tract - more transmissible & immune response weaker However D614G increases load in URT without reducing loads in LRT. One VOI infects lower respiratory tracts, perhaps to evade nasal swabs.
WOULD IT BE LESS DEADLY IF KIDS GET IT WHEN YOUNG? MIGHT NOT BE BECAUSE OF SHORT DURATION OF IMMUNITY
Another idea is that if we all get it when young, then it may be less serious by the time we are elderly.
However the paper critical of the avirulence theory says that the evidence for that isn’t that strong either. Our immune response to it fades rather quickly because of the way it hides from the immune system. Also variants might evade the immune system.
COVID could become less virulent by infecting kids when it's less severe so adults are already immune. However immunity from COVID is short lived. When variants evolve to escape immunity, this may not reduce virulence
This is where they cover that point in the paper
I go through these papers here,this article is a reworking of the presentation - I also have a couple of videos there going through the papers
IF COVID EVOLVES TO BE MILD, ONE GROUP OF SCIENTISTS WILL SAY “TOLD YOU SO” AND IF IT STAYS SEVERE ANOTHER GROUP WILL SAY THE SAME THING
So, if Omicron is a milder version then the virologists won't be shocked and a few of them will say "look at my paper I told you so :)"
So it is possible it is milder but too soon to say for sure. It is still causing hospital cases in unvaccinated people, so it's certainly not as mild as a cold yet but many cases are mild.
HOW DO WE STOP MORE VARIANTS IN THE MEANTIME? - IT’S QUITE SIMPLE - LESS TRANSMISSION - LESS VARIANTS
Skip to: Yes vaccines work
We can end the pandemic - at least reduce to very low transmission - much faster if we keep transmission low, which stops variants as we vaccinate everyone.
Variants won't escape vaccines instantly.
But high levels of transmission + high levels of vaccination favour gradual vaccine escape.
Dr Tedros put it like this:
"It's quite simple. More transmission, more variants. Less transmission, less variants".
I go into all this in some detail with cites etc and link to his video here.
More on that here
In the same talk where Dr Tedros talks about how variants can evolve in ways we can't predict, he goes on to say that the bright light of the vaccines have blinded countries to the need to continue with the other tools to stop this virus spreading and overwhelming our health systems.
But in too many countries and communities, the bright light of vaccines has also become a blinding light to the continued need for other tools to stop this virus spreading, to stop it overwhelming our health systems, and to stop it killing.
Vaccines save lives, but they do not fully prevent infection or transmission.
Suppressing transmission is essential until we have high levels of vaccination in every country.
Until we reach high levels of vaccination in every country, suppressing transmission remains essential.
This doesn’t mean lockdowns which are a last resort in the most extreme circumstances.
Instead it needs to be a response tailored to the circumstances - Vaccines AND not Vaccines OR
We don’t mean lockdowns, which are a last resort in the most extreme circumstances.
We mean a tailored and comprehensive package of measures that strike a balance between protecting the rights, freedoms and livelihoods of individuals, while protecting the health and safety of the most vulnerable members of communities.
Ending this pandemic is not about vaccines OR, it’s about vaccines AND.
WHO say to continue to do the same things as before
What's really important as an individual is to lower your exposure - these proven public health measures have never been more important
- wearing of a mask
= making sure that it's over your
nose and mouth
- with clean hands
- making sure you avoid crowded spaces
- be in rooms where there's good ventilation
- and when it's your turn get vaccinated
See also my article about the Swiss Cheese model - the many layers of protection:.
Although I mention Delta on the graphic, it’s the same for all the variants.
With delta especially - need vaccines + #DOITALL
Delta has extra holes in vaccine layer - so we need to use the other layers better
It's just a disease. It’s not a comic book mutant!
Recommended actions for people
The most effective steps individuals can take to reduce the spread of the COVID-19 virus is to keep a physical distance of at least 1 metre from others; wear a well-fitting mask; open windows to improve ventilation; avoid poorly ventilated or crowded spaces; keep hands clean; cough or sneeze into a bent elbow or tissue; and get vaccinated when it’s their turn.
WILL WE END UP IN LOCKDOWN AGAIN? CAN’T SAY - BUT THE ANSWER IS TO #DOITALL AND GET VACCINATED - THE MORE YOU DO THAT THE LESS NEED FOR EXTREME MEASURES LIKE LOCKDOWN
Skip to: Wear a mask and #DOITALL
Short summary - #DOITALL, break possibilities for chains of transmission wherever you can. The more you do that, the less the risk of lockdown. Vaccination, masks, physical distancing, testing, isolation, quarantine, ventilation, everything. People don't see the connection but they only end up in lockdown over and over because they don't do those other things thoroughly enough.
Omicron is already in the UK. As of writing this, there are 22 confirmed cases in the UK and 200 probable cases. There are likely at least as many in the USA but UK has far better genomic surveillance than the USA.https://bnonews.com/index.php/2021/11/omicron-tracker/
The main thing is to step up on vaccination to be prepared for it - and to reduce cases per day as much as you can. The fewer cases of Delta you have, the easier it will be to stop Omicron.
The UK at last is introducing masks and the masks are being worn. This will help, also some mask wearing in schools.
Also people will start to take it a bit more seriously as they do with every new variant.
The R number in the UK is just a bit above 1 at present, 1 to 1.1. This means if you can stop 1 in 10 of the chains of transmission cases per day will start to go down instead of up.
If Omicron is indeed significantly more transmissible then it will help to get the cases per day way down before Omicron spreads
What is more important? For others in a shop or public transport to be able to see your smile - or to protect them from a potentially deadly disease?
This is a graphic I did to promote mask wearing:
: let others see your smile
: save others from
Eyes can smile too
Image credits: File:Coronavirus COVID-19 pandemic.jpg - Wikimedia Commons
This is a scientific study which shows that mask wearing leads to people smiling with their eyes more than they did before mask wearing.
Smiling for a photo.
With mask - more use of Orbicularis oculi which raises cheeks and creases skin at corner of eyes.
In South Africa it was spreading with almost no competition from Delta, because South Africa had brought Delta right down, then Omicron started to spread.
The WHO say it infects people who already had Delta - so that much we know, natural immunity to Delta doesn't stop it spreading as much as it stops Delta.
Preliminary evidence suggests there may be an increased risk of reinfection with Omicron (ie, people who have previously had COVID-19 could become reinfected more easily with Omicron), as compared to other variants of concern, but information is limited.
So that suggests it will reinfect populations previously exposed to Delta faster than Delta can do (Delta can also reinfect). We have lots of people in the UK previously exposed to Delta.
This is not the R0. It’s the Re, the effective reproduction number taking into account the measures being taken in South Africa to stop the spread,
The Re (effective reproduction number) has increased from 1.47 to 1.93 - that’s a 32% increase.
I.e. each person on average infects 1.93, where before for the same region it was 1.47. As you can see the R0 keeps wiggling up and down, so - it’s not very conclusive but it’s quite a steep rise and combined with the other evidence may show an advantage of transmissibility
Slide from this point in the press briefing
It was a very sudden spike. In a few days it went from very controlled up to levels similar to previous peaks for COVID in South Africa.
From the WHO dashboard for South Africa
This is why it is sure to be classified as a variant of concern by the WHO.
If it spreads as fast as in South Africa - their Re increased 32% with Omicron with preliminary estimates.
This means to get it steady in the UK we need to block about a quarter of all current transmission.
That is certainly possible but whether we can do that without a lockdown I don't know. Scientifically we can if people do the right things. The big question is whether the general public and the governments do the right things to avoid a lockdown - and I don't know the answer - nobody knows the answer to that. But on an individual level we can all do what we can to help.
SUPPOSE IT INCREASES TEN-FOLD EVERY 10 DAYS - IT COULD SURGE FROM 100 A DAY TO 100,000 A DAY IN 30 DAYS - IF THAT HAPPENS RESTRICTIONS OF SOME SORT SEEM LIKELY - MASKING UP AND #DOITALL COULD PREVENT IT
Also we don't know how serious it is. Currently UK is running at 40,000 cases per day.
In South Africa it increased 10-fold in 10 days.
Suppose for instance that 100 of those 40,000 cases today are in fact Omicron. Then in 10 days that would be 1000, then 10,000, then by this time next month, 100,000 Omicron cases a day.
So that gives an idea of how fast it could increase in a worst case scenario. Then unless it is far milder than Delta such a big surge would once more overwhelm our hospitals.
In a situation like that, I expect the UK to go into lockdown because we don't have the discipline to stop it without a lockdown. But we do lockdowns very well in the UK.
But our lockdowns can be far more targeted this time around, as they know better what causes it to spread and what doesn't.
For instance closing or restricting hotels / restaurants, and closing or restricting night clubs, and restrictions on large gatherings - and basically moving back through the restrictions that were lifted before.
One technique the UK knows works is surge testing - rapidly test many people with PCR tests and isolate everyone who tests positive. After the success with Bolton several trials were done - it was promising but this was just before the Delta surge - with Delta already rising. Eventually it got overwhelmed with all the Delta cases.
However it could perhaps be scaled up much more. This can help fill the gaps in contact tracing and reach people you might not reach otherwise.
This is a technique the UK could take off the shelves and use again:
What would make a huge difference would be to be more careful about preventing transmission within households, quick quarantine of contacts and very fast isolation of a case away from the rest of the household as soon as you have symptoms, keeping physically distanced and with the case to wear masks at home as well as others in the household when they are in contact, as soon as anyone gets symptoms.
Whatever the government does - if anyone in your household gets it, you can do these things, do your best to prevent it spreading to anyone else in your own household. Same if anyone becomes a contact in your household.
There is a far higher risk of getting COVID from someone else in your household than from any other setting. This table shows the result of one meta-review
So if enough people protect their households in this way, it could block a significant % of all transmission.
This is what the WHO recommend if you get any cases in your household.
Not just for vulnerable cases, for everyone.
In more detail then you can also take many other precautions to protect others in your household.
Isolate in their rooms and only a designated carer sees the case, and especially if the UK gov was to support isolation away from home in quarantine / isolation hotels like NY does - for those who want it - and supported isolation.
And - to protect them most of all, isolate as soon as you develop symptoms while waiting for the test result.
Infographics from here:
Anecdotally many people don't even seem to know the importance of preventing transmission in households. Who wouldn't want to protect others in their own household if they knew of a way to do it? But through a false analogy with flu, many don't realize how much potential there is to block COVID in your own house.
If we all did this it would make a huge difference.
SUPPORTED ISOLATION AWAY FROM YOUR HOME IS THE SAFEST WAY OF ALL TO PROTECT THE REST OF YOUR HOUSEHOLD, IF FEASIBLE
By far the best way to protect your household is to isolate away from them completely in a COVID hotel or quarantine facility.
There’s a bit of a history here that may explain the low uptake of action to stop transmission in households.
Through most of 2020 the WHO emphasized over and over that we need to provide the capability to isolate people away from their own household - to provide that capability.
This was misrepresented by some journalists as the WHO wanting to take people out of their homes.
After that it was very difficult to get the message out about how you can prevent household transmission. Because it got associated with this idea that the government or the WHO want to take people out of their homes.
That’s not it at all! This is something governments can offer as a service to their people for those who are unable to isolate properly at home, or who want the extra protection for the rest of their household you get by isolating in a separate building from them. Still in contact via zoom chat of course.
New York provides this as a service for those who need it for free. New Zealand does for its residents too and China does amongst others. The more we can do this the better.
, Mike Ryan for WHO - if given one golden wish to control COVID19 - it's for each case that tests positive to isolate properly and all contacts to quarantine properly - isolated from anyone else - not to imprison but to break chains of contact
EARLY STUDY FROM CHINA SUGGESTED WEARING MASKS HABITUALLY AT HOME BEFORE THE FIRST CASE IN YOUR HOUSEHOLD PREVENTS 79% OF HOUSEHOLD TRANSMISSION
In China some people habitually wore masks at home, all the time when there was community spread in the area. Households that were wearing masks already before the index case got infected had a fifth of the risk of transmission to other members of the household than ones that don't. That was in the first wave early on and as far as I know there haven't been any follow up studies since then to test this. That study is mentioned here:
In a study of 124 Beijing households with > 1 laboratory-confirmed case of SARS-CoV-2 infection, mask use by the index patient and family contacts before the index patient developed symptoms reduced secondary transmission within the households by 79%.
AFAIK that is still the only study of habitual mask wearing in households before anyone gets infected as a way to control COVID. If anyone reading this knows of any other such study please let me know, thanks!
Some of the people I talk to do this, if they have vulnerable members. I haven’t seen it recommended by the CDC or WHO but it may help.
This would work by reducing transmission in the presymptomatic and mild symptoms stage of infection before you know you have COVID.
Best if everyone wears masks, masks work best as a source control so you are also protecting the others if you have COVID unknown to you. But some protection the other way too.
Why would masks stop transmission in shops and not at home? Surely worth a try.
Likely it also will help with other respiratory diseases too. I wish someone would look into this and advise us properly - not seen it mentioned anywhere as a possible mitigation measure except when someone in the house already is a case or contact.
IF HABITUAL MASK WEARING AT HOME DOES WORK - IT COULD MAKE A VERY SIGNIFICANT DIFFERENCE TO THE R NUMBER
If this is indeed true, habitual mask wearing at home for a few weeks during times of high community spread could potentially make a dramatic difference. Point of clarity. I'm talking about a voluntary measure here. It's not practical and surely not desirable for a government to mandate masks at home.
If the data did show that habitual mask wearing reduced the risk of passing on Omicron 5-fold (say) - it might be only a few families decide to do it - maybe only with highly vulnerable members. Still worth it for those families, to give them an option to reduce the risk.
But it's possible that many might decide it is worth wearing masks for 2 weeks to get a fifth of the risk of infecting household members during the surge and as a collective thing to help control the surge, working together as a society.
Let’s try some figures. Please note this is hypothetical - the details would depend on whether that study is replicated and whether masks have the same advantage for Delta and Omicron as for ancestral COVID.
Suppose that Omicron increases transmission 32%.
Now suppose that habitual mask wearing at home reduces transmission 79%.
Several studies suggest the majority of transmission is in households, Suppose that just 50% of transmission is in households.
If we can block all except 21% of transmission in households, transmission is reduced from 100% to 50 + 50*21/100 = 60.5%
The Re in the UK is currently 0. 9 to 1.2 in the worst affected regions. An increase of 32% would take that to a maximum of nearly 1.6. But (if a reduction similar to the Chinese data from 2020 applies today) habitual mask wearing at home in the most risky regions during high community spread would take even 1.6 down to below 1 even if only half the transmission is in households.
This makes sense especially if anyone in the household is very vulnerable, For everyone to just wear masks all the time at home for as long as community spread is high. That way if any get COVID there is likely to be a very low chance of passing it on to the vulnerable person.
This could be especially useful for people who have high risk of passing it on, such as those living in crowded houses with lots of interpersonal contact. Latinos have nearly a 1 in 2 chance of getting COVID from a contact in their household (45.8%) by one study compared to only 32% for the average in America.
I've not seen anyone suggest this advice. It just makes logical sense and is worth a try, especially if one has a vulnerable person in the house.
NOT FOUND RECENT STUDIES ON HABITUAL HOUSEHOLD MASK WEARING - SUGGESTION - RANDOMIZED CONTROL TRIAL OF - SAY - 1000 HOUSEHOLDS THAT AGREE TO COMPLY IF RANDOMLY SELECTED TO ALL HABITUALLY WEAR MASKS
Perhaps we could use a Randomized Control Trial to test if this works. Interested in any comments on whether you think this is feasible and how to do it.
We could select, say, a 1000 families of four that are willing to mask up at home for three weeks when community spread in their area is above 1 person in 1000 infected per day.
Of course many won’t be interested, but some will be
- Asian communities because of cultural acclimatization with mask wearing
- Households with immunosuppressed people
We just need 1000 households to agree. Then from that list, select half of them at random to wear masks for three weeks, and the other half don’t. This then is a randomized control trial since the two samples are equivalent, selected only by randomization
AFAIK nobody has tried a Randomized Control Trial where households in areas with intense community spread are randomly selected to wear masks habitually at home to test for reduced transmission.— Robert Walker BSc, science blogger & fact checker (@DoomsdayDebunks) August 2, 2021
The observational study for ancestral suggests an easily detectable 79% reduction! https://t.co/tb9LoegW3I
As I explain there we could have answers in a few weeks, if the difference is as striking as those early Beijing results suggest. We could also use the same methods to test different types of mask. E.g. does an n95 mask provide significantly more protection? This could be useful data for mask wearing generally in other situations.
Has anyone done such a trial, or is anyone proposing one, anyone know?
TOTAL OF ALL COVID DEATHS PER MILLION SO FAR IN USA COMPARABLE TO 106 DAYS NON PANDEMIC DEATHS FROM INFECTIOUS DISEASES IN 1900 - COVID DEATHS IN LAST YEAR COMPARABLE TO 60 DAYS NON PANDEMIC DEATHS IN 1900
Also though COVID is definitely a serious disease - the total deaths so far from COVID in the USA are equal to a little over 100 days of deaths from infectious disease in 1900 back before modern medicine when there were many deadly diseases like smallpox which is now eliminated, also polio, measles and flu also was much more serious than today with the medicine of 1900.
Back in 1900 there were many deadly disease now we just have flu. All the deaths so far in the USA from COVID are equivalent in deaths per million to 70 days of deaths from infectious diseases in 1900
It's not as bad as spanish flu in terms of numbers of deaths
All the deaths in the USA in the last year from COVID are equivalent in deaths per million to 60 days of the Spanish flu at its peak
Deaths in 2020-1 from COVID compared to yearly deaths from all infectious diseases in USA from 1900 to 2000
US deaths in last year from COVID in deaths per 100,000 = 60 days of spanish flu and 70 days of deaths in 1900 from all infectious diseases
70 = 365*1.54/8
60 = 365*1.54/9.5
Positioning of lines calculated in pixels as
200+53*(2-1.36)/2 = 217
200+53*(4-1.54)/2 = 265
200+53*(4-1.3)/2 = 272
In 1900, 194 of every 100,000 U.S. residents died from TB; . Achievements in Public Health, 1900-1999: Control of Infectious Diseases We also had deaths from diarrhea, intestinal disease, etc all preventable today.
Here for comparison are the deaths in the last year in the UK, USA and Peru:
Figures calculated as
From this page
There is no way we could be wiped out by a deadly disease. Even if a disease was to spread as deadly as smallpox with a case fatality rate of 30%, and with no vaccine or cure we wouldn't all die. Smallpox
Back then also many died of TB.
The COVID vaccines especially with boosters are working against all variants especially for stooping severe diseases.
Remember this is a booster that was developed for ancestral COVID, not any of the variants. Yet it is giving very high levels of immune response to Delta.
I go into more details herehttps://debunkingdoomsday.quora.com/Pfizer-booster-seems-to-give-very-high-levels-of-COVID-protection-if-so-it-will-make-a-big-difference-once-everyone-ca
Flu is the ONLY virus to evade vaccination every year - except now, of course, COVID. But so far COVID has nothing like the level of vaccine evasion of flu.
HOW FLU IS SO UNUSUAL - EIGHT SEGMENTS THAT CAN BE SWAPPED EASILY WITH THE SAME SEGMENT IN ANY OTHER FLU VARIANT
SARS-CoV2 can mix / match different variants with recombination but this is very rare. Only one confirmed example so far.
Recombination is a natural process. It happens when two different strains infect the same cell. Both start replicating and since there are bits of both in the cell sometimes you get a new virus that is part one strain and half the other strain.
The actual new variant is not a variant of concern - Delta seems to win against it but it spread widely in early to mid 2021. The main interest is just that it is the first reasonably certain identification of a recombination event.
One concern was that there might be a recombination of Delta with, say, Beta (which is far more evasive for both vaccine and natural immunity against ancestral). But that hasn't happened, or if it has, then it's not been viable enough to spread.
This new variant doesn’t seem to be a recombinant of existing variants.
But flu has a very unusual design which makes a form of recombination very easy.
Virus for COVID - one strand of positive sense RNA
Flu virus - 8 segments of negative sense RNA
Images: Flu from File:Flu virus.jpg - Wikimedia Commons
- positive sense RNA means it can be translated directly into proteins
- negative sense RNA is used to make mRNA which then makes proteins. Negative sense RNA can’t be used directly to make proteins. It works more like DNA which makes messenger RNA.
So they are very different, you couldn’t take a bit of a flu virus and stick it into a COVID virus and expect it to work.
Flu and COVID are both respiratory diseases - that's like saying cows and hedgehogs are both mammals. This doesn't mean they will behave the same way.
Expecting flu to behave like COVID is like expecting … a cow to behave like a hedgehog because both are mammals
There are differences in the
- Treatment (drugs that work for COVID are not suitable for flu)
- R0 (5–8 for delta, up to 1.5 for flu)
- superspreading (flu doesn’t do superspreading)
- evolution rate (faster for flu, it’s able to exchange any of its 8 segments with any other flu virus)
- vaccine efficacy (much higher for COVID)
For instance the WHO see no sign that COVID is seasonal. It surged in the UK in summer, flu never would do that. COVID can't evade vaccines as well as for flu and the vaccines are already far more effective than ever achieved after many years of research for flu.
WHY MOST VIRUSES FIND IT SO HARD TO EVADE VACCINES - ANTIBODIES BLOCK MANY DIFFERENT TARGETS ON THE VIRUS AND THEY BLOCK THE VIRUS EARLY ON WHEN NUMBERS ARE LOW
Most vaccines never need to be altered and there is essentially no vaccine evasion. To take a couple of examples, the MMR vaccine hasn't had to be updated since 1971. Salk's inactivated polio vaccine (IPV) has had only minor updates since 1954 and the changes weren't due to vaccine evasion. History of polio vaccination
This is probably because vaccines present the immune system with multiple targets to recognize. The more targets, the harder it is for a virus to evade them all in one go, and evading one of the antigen targets is not enough to give it an evolutionary advantage.
By contrast antibiotics target specific cell processes that a microbe can adapt to avoid the antibiotic.
Another difference is when they act. Vaccines act early on when there are few pathogens. Antibiotics are used only later when there are millions of microbes in the body.
I expect the boosters to still be very effective against omicron, and if not next generation vaccines will be even more effective.
As I write this November 2021, there are 107 vaccines in clinical trials, 15 approved for emergency use and 8 fully approved by various countries.
‘By this time next year we should have
- 100 new vaccines
- Including Hexapro tweak made low cost using hen’s eggs with higher antibody levels even than Pfizer
- Gritstone bio which targets innards for T-cell response as well as spike
- May have a pancoronavirus vaccine that targets innards of the virus common to all or most coronaviruses for T cell responses - works not just with all COVID variants but also SARS and MERS
- vaccines tweaked to variants
- Probably a dozen or more new therapeutics for COVID
- Vaccine hubs mean Africa and other low income countries are developing their own new mRNA vaccines, protein subunit vaccines like Novavax and viral vector vaccines like AstraZeneca
Vaccine efficacy at stopping transmission may well be in the high 90s by then.
All this capacity will also put us well on our way to eliminating several other viruses
Also much more vaccine equity.
This might even lead to a pancoronavirus vaccine that works with all coronaviruses. Or with closely related ones e.g. for MERS, SARS and COVID in one vaccine and all variants of them all
It's early research so far but the results are promising for a vaccine that might at least protect against closely related viruses, E.g. an experimental COVID vaccine in pigs unexpectedly protected pigs from symptoms of PEDV, a different coronavirus that kills 1 in 10 pigs.
It's currently in animal trials. He estimates it would cost less than $1 per dose for weaker economies.
Gritstone Bio's vaccine candidate already in clinical trials may protect against all variants of COVID including future ones not yet evolved.
2nd generation vaccines like Gritstone may be even more effective than Pfizer and work against all variants
Trains B cells to make antibodies that stick to the spikes stopping virus entering cells
Trains killer T-cells to recognize virus innards. Prevents virus making copies inside cells.
Virus innards change slowly, common to all variants.
Gritstone should be more effective and suitable for immunocompromised with suppressed B cells.
It recently got support of CEPI:, the Coalition for Epidemic Preparedness Innovations, They provided US$20.6 million for a phase 1 clinical trial.
This is part of CEPI’s program for “next-generation” COVID-19 vaccines that can be used against COVID-19 variants.
CEPI’s portfolio of “next-generation” vaccines currently includes SK bioscience’s nanoparticle vaccine candidate (GBP510), the University of Hong Kong’s intranasal vaccine candidate, VBI Vaccines’ virus-like particle candidate, and ZerunBio’s recombinant vaccine candidate.
They will make it available globally through COVAX as part of the CEPI funding deal.
As part of the latest CEPI funding deal, Gritstone has agreed that if it is successful in developing a universal COVID-19 vaccine, it will be made available globally through the COVAX facility, which is sponsored by CEPI, the vaccine funding body Gavi, and the World Health Organization, meaning that developing countries ought to be able to gain access to the vaccine.
I cover this and several other advances here:
OTHER NEW VACCINES DESIGNED TO BE EASIER TO MAKE, STORED AT HIGH TEMPERATURES (FRIDGES), LICENSED FOR FREE TO WEAKER ECONOMIES AND EXPECTED TO GIVE A STRONGER IMMUNE RESPONSE EVEN THAN PFIZER
ButanVac, in clinical trials is grown in hens eggs, 5 or 10 to an egg instead of 1 to 2 to an egg. License free to weaker economies. Spike proteins stuck in the shape just before virus invades a cell which should trigger a far more effective response than natural immunity.
Pfizer / Moderana used a similar technique (the 2P tweak) but this new Hexapro tweak is even better.
Spike proteins more stable
Immune response stronger
Stored at high temperatures
In phase 1 trials
Free license for weaker economies
Grows in hen's eggs
Similar new vaccines in Brazil, Mexico, Thailand & Vietnam.
5 times more vaccine per egg than for flu vaccines
This is one of several vaccines all based on the same idea, developed by the University of Texas. The vaccine is called NDV-HXP-S. The scientists own the patent but they license it for free to the weaker economies.
For more on this
. New vaccine technology for COVID entering phase 1 - can grow in hens eggs - low cost and licensed for free to weaker economies - end run around vaccine intellectual property restrictions of wealthy countries
So the science is continuing with astonishing speed.
I cover this and several other advances here:
WE CAN VACCINATE VERY FAST (AN ENTIRE COUNTRY IN DAYS) IF WE MOBILIZE TO DO IT - BHUTAN TOOK ONLY 11 DAYS TO VACCINATE 90% OF ADULTS - AND IN 1980 BRAZIL VACCINATED ALL ITS SCHOOL KIDS AGAINST POLIO IN ONE DAY - BOTH ARE COUNTRIES WITH MAJOR LOGISTICAL CHALLENGES AND REMOTE INACCESSIBLE COMMUNITIES
Also you may think from the US, UK etc that it has to take months to vaccinate a population. We congratulate ourselves for our very fast vaccination.
It’s far faster than anything we’ve done, at least in recent times.
But with the right preparation, actually it can be done FAR faster. Bhutan vaccinated its entire population in 11 days.
That’s a lot faster even than Israel. And Bhutan is not an easy place to vaccinate, its mountainous much of it is rural.
What Bhutan had in its favour is that they were lead by medical practitioners - the prime minister, health minister and foreign minister of Bhutan are all medical practitioners.
Bhutan had the same problems of the infodemic and vaccine hesitancy of other countries.
They used 3,000 health workers to vaccinate their 800,000 people and 22,000 volunteers helped to prepare for it, raising awareness, dispelling misinformation, helping to carry the vaccines to remote locations.
It needs an “all of government all of society” approach. Bhutan shows it doesn’t need high GDP per capita, $3,316.18 compared to $65,297.52 for the US and $2,229.86 for Nigeria. (using google for the GDP per capita for those countries, if it got it right).
This is a graphic I did to summarize it:
You might think - well Bhutan can do it - but what about the UK or the US? Is this something only small countries can do? Well - what about Brazil?
Brazil has a reputation for fast vaccination - but hasn’t had the chance to show how fast it can vaccinate in this pandemic so far, because of the limitations of supply. But on June 14, 1980 Brazil achieved a far faster vaccination rate than even Bhutan did.
“On June 14, 1980, Brazilian public health officials launched the largest mass immunization campaign to combat polio in public health history. Over 300,000 people, primarily volunteers, manned 90,000 vaccination posts and health facilities, and succeeded in vaccinating 17.5 million Brazilian children in a single day.”
Dissertation on https://audra.american.edu/islandora/object/thesesdissertations:118/data...)">Polio and the politics of policy diffusion in Latin America.
17.5 million children out of a population of 120.7 million vaccinated in one day. That would reach 60% in four days if they could keep it up to the rest of the population.
Brazil like Bhutan has many remote hard to reach places in the rainforest and so on.
Weaker economies CAN vaccinate fast. That’s not the hold-up at present. The hold-up is just the supply.
Once we have the vaccine supply, we can end it very fast if we choose to.
WHO'S FIRST TECHNOLOGY TRANSFER HUB IN AFRICA WILL MAKE LOW COST VACCINES BASED ON MRNA (LIKE MODERNA), SUBUNIT PROTEINS (LIKE NOVAVAX) AND VIRAL VECTORS (LIKE ASTRAZENECA)
This will be the first facility to make vaccines in AFrica. The WHO technology transfer hub in Africa is hopefully first of many.
It’s an mRNA hub so far, the aim is to be able to make mRNA vaccines in Africa where most of the subsidiary patents don’t apply - so South Africa will be able to make mRNA vaccines for the rest of Africa.
They want to copy the Moderna vaccine as they provide their patent for free to weaker economies but Moderna wouldn't share information on how to make the vaccine. There are many tweaks and steps to the process and without this information the vaccine will be much harder to make and to get approved.
So WHO + Biovac + Afrigen biologicals are trying to make a new mRNA vaccine based on the patent, but without Moderna's help so they have a lot more work to do from scratch.
This is Afrigen's tentative timetable for their mRNA vaccine.
They have two candidates, the Moderna clone and one from India.
They believe that even without Moderna’s help, they can have the first “Good Manufacturing Processes batches ready by the end of September 2022.
That will be a very major thing for future pandemics and other diseases too - and for COVID too if there are still vaccine shortages by then.
The long-term plan is self-sufficiency, for a future where Africa makes enough vaccines for its own people, but right now Africa imports around 90% of its vaccines.
The technology transfer hub will help to change this, helping African manufacturers to move to more advanced levels of production where they can make mRNA vaccines from start to finish without any outside support.
Many other vaccines use the same mRNA technology that we’ll be transferring, such as vaccines against Ebola, Lassa Fever and Marburg, and eventually this mRNA technology could even be used to produce vaccines against HIV or tuberculosis.
WHO plan to use the same method for
- subunit proteins (like Novavax) and
- viral vectors (like AstraZeneca) etc.
and to set up many other vaccine hubs in weaker economies and training in vaccine manufacturing, so we never get this vaccine inequity again.
For more on this:
Skip to: We don't have to live with the virus
One of the keys to the success of the Pfizer vaccine is the so called “2P tweak” which helps stabilize the spike protein in the shape it gets into just before it enters the cell.
The virus is a shape shifter, constantly changing the shape of the spike to confuse the immune system and sometimes with a sugar molecule (glycan) also covering it to hide it.
The 2P tweak stabilizes it in the shape the immune system needs to recognize for the best immune response.
The Hexapro tweak does the same thing but a much higher % of the spikes get stabilized with the Hexapro tweak, which means you get
- stronger antibody response
- less vaccine needed
- the vaccine is stable at a higher temperature
Texas has licensed this even better Hexapro tweak for free to weaker economies.
Brazil is using it for Butanvac which will be grown in hen's eggs based on the Newcastle virus.
This is the same one Vietnam is using. The 2P tweak - Why Pfizer and Moderna are so effective as vaccines - this tweak could be used by other vaccines like Astra Zeneca - and 2nd generation vaccines may use the even more effective Hexapro tweak published July 2020
The positive thing here is many academics in stronger economies are fully behind technology transfer.
Including Ugur Sahin, CEO of Biontech, basically inventor of Pfizer, fully supports mRNA hub in Africa.
Then 2 vaccine makers, Novavax & AstraZeneca support technology transfer.
This is Dr Maria van Kerkhove, technical lead for the WHO’s COVID response
Transcript and my short summary to help autistic readers.
I have to say I don't like the phrase "living with the virus". To me it almost feels like we've given up.
But at the same time what we're thinking through are these different scenarios what what will COVID19 look like in the next three, six, nine months?
What are the possible scenarios that we we can look through.
I don’t like the phrase “Living with the virus”, it feels like we’ve given up.
What are the possible scenarios?
We have the tools right now that we could drive transmission down so low and we can minimize the severity, we can minimize the deaths because we have enough vaccines to be able to do that and those who are most at risk around the world, we just haven't used them properly.
We already have the tools to drive transmission down so low, and we can minimize deaths if we get the vaccines to the right people. We just haven’t used them properly.
It may become endemic but that doesn't mean that the virus is everywhere all the time at this level.
It means that it is in specific geographic areas, and I can envision many different types of futures.
I hope that we can drive transmission down as quickly as possible so that we have minimal levels of transmission around.
It may become endemic - but that means in specific geographical areas. Not everywhere all the time. I can envision many different futures.
I hope we can drive transmission down as quickly as possible - and have minimal levels of transmission.
Listen to the rest of the Q/A here
ENDEMIC DOESN’T NEED TO MEAN HIGH NUMBERS OF DEATHS - POLIO, MEASLES, TUBERCULOSIS, ALL USED TO LEAD TO THOUSANDS OF DEATHS PER YEAR IN EVEN THE MOST ADVANCED ECONOMIES - NOW ONLY FLU DOES THAT
If COVID does become endemic then there's a big difference between endemic like measles with just a few deaths a year per country and with some countries measles free - and hyperendemic like flu with thousands of deaths per year per country. We used to have many hyperendemic deadly diseases - polio, smallpox, measles, tuberculosis and flu.
Also I get some people worry that COVID will make us extinct. No there is no risk of this. It’s not enough to even significantly dent our population.
Our COVID deaths are high for our times, they have been the leading cause of death in many countries - but transport someone from 1900 to today and they'd be astonished at how few people die of disease in our world even in the middle of the pandemic.
Child mortality back then was very high. Getting on for half of all children died before they reached adulthood in Victorian times.
Back then this was normal, they didn’t know it could be different.
WE HAVE ELIMINATED MANY OF THOSE DISEASES THAT TROUBLED HUMANITY IN 1900 - SOME ALMOST COMPLETELY - FLU IS THE ONLY HYPERENDEMIC DEADLY DISEASE LEFT
Smallpox has been eradicated from the world. Many countries are now polio free
Many countries are measles free (only imported cases and transmission locally lasts for less than a year). The UK recently lost its measles free status but the US still has it.
But cases of measles per year in the UK are very small. UK lost measles elimination status at 991 confirmed cases in 2018 (later updated to 998)
Globally deaths due to measles continue to fall.
Tuberculosis is just about gone as a result of modern antibiotics.
We have more than halved mortality from all causes since 1900 and most of that change is due to eliminating most of the most deadly infectious diseases and greatly reducing the deaths from flu.
Reduction in infectious diseases 1900 to 2010. Only influenza is left of the hyperendemic diseases, greatly reduced
Now the only hyperendemic disease left is flu.
As we saw, COVID can't evade our vaccines every year like flu. The slow evasion of delta and Beta is nothing like the very fast efficient evasion of flu.
Because of the way vaccines work, experts think there's an excellent chance of developing a vaccine that will stop all variants so it can't evade it ever again.
HYPOTHETICAL WHAT IF - IF COVID WAS ENDEMIC AT TEN TIMES HIGHER LEVELS THAN MEASLES IN THE UK - THAT WOULD BE 100 DEATHS A YEAR
To take an example, just a for instance, if we can reduce cases per year to, say, 10,000 or less with a more effective vaccine, say, with perhaps 100 deaths per year, we’d declare the pandemic well over, even though COVID would remain endemic. But at that rate, with so few deaths it, would no longer be a hyperendemic deadly disease like flu.
Even those 100 deaths would likely go down with more therapeutics - and this is based on the reductions of deaths for the original vaccines against delta. The 2nd and 3rd generation vaccines may well be far more effective. It might be that 10,000 cases aa year lead to only 10 deaths per year by the end of 2022 :).
This is of course not a prediction. It’s just a hypothetical what if to give you an idea what “low level endemic” can mean.
This is extrapolating a bit beyond what Dr Maria Van Kerkhove said.
It may become endemic but that doesn't mean that the virus is everywhere all the time at this level.
It means that it is in specific geographic areas, and I can envision many different types of futures.
I hope that we can drive transmission down as quickly as possible so that we have minimal levels of transmission around.
It may become endemic - but that means in specific geographical areas. Not everywhere all the time. I can envision many different futures.
I hope we can drive transmission down as quickly as possible - and have minimal levels of transmission.
Listen to the rest of the Q/A here
She didn’t specify what she meant by specific geographical areas and not everywhere all the time.
However, Taiwan, Tonga and Bhutan show no sign of opening up yet and China is going to be very cautious and only open up once it has such good vaccine coverage that outbreaks remain easy to control.
With policies like that, and if we get a good enough 2nd or 3rd generation vaccine, could these countries not remain COVID free in the sense of having no sustained local transmission?
Could these countries remain COVID free in the same way that many countries are measles free?
But we don’t need to achieve countries with COVID free status to end the acute stage of the pandemic and end the global health emergency.
THERE ARE MANY DISEASES WE ARE ALREADY ELIMINATING LOCALLY AND SOME ARE CLOSE TO BEING ELIMINATED GLOBALLY
Skip to: Diseases that could be eradicated
Longer term with the vastly increased vaccine capacity in weaker economies, we may be able to eliminate other diseases too.
We are well on the way to eliminate polio, it is likely to be the next human disease to be completely eradicated. Malaria is already eliminated in many countries.
There are many more we can target. The advances in vaccine research in the last year have been extraordinary.
Where will we be a decade from now in the early 2030s?
Perhaps on the way we can eliminate COVID and flu too - apart from the animal reservoirs
Most of these can be eradicated using vaccines
- Dracunculiasis (Guinea worm disease) Eradication of Guinea Worm Disease--Case Statement now free from a total of 199 countries, territories and areas Dracunculiasis eradication: intensifying surveillance amid continued zero human cases in Ethiopia and Mali
- Lymphatic filariasis Global Programme to Eliminate Lymphatic Filariasis
- Measles (already eliminated from the Americas as an indigenous disease Measles
- Mumps Mumps
- Hepatitis B
- Polio (already eliminated from the Americas as an indigenous disease 10 facts on polio eradication
- . Taeniasis/Cysticercosis (pork tapeworm) - this could be eliminated by vaccinating pigs
- . Yaws and other endemic treponematoses
- Malaria Overview of malaria elimination Has been eliminated from many countries worldwide now. Countries and territories certified malaria-free by WHO
- Onchocerciasis or river blindness Onchocerciasis (river blindness) Has been eliminated from Colombia, Ecuador , Mexico and Guatemala
. Sources - I made these lists using:
They don’t mention hookworm which has been eradicated from some parts of the world and could be eradicated worldwide. It is in the list of the nine diseases that could be eliminated here:
The International Task Force for Disease Eradication looked at several others, some could be eradicated locally. This is from 2008, if you know a later update do say:
- Disease considered as candidates for global eradication by the International Task Force for Disease Eradication
If I've left any out do say, thanks!
DISEASES THAT CAN BE ELIMINATED AS A PUBLIC HEALTH PROBLEM IN HUMANS INCLUDE MENINGITIS, HIB, YELLOW FEVER, DENGUE FEVER, SLEEPING SICKNESS AND HIV
There are also many diseases that can't be eliminated because they have reservoirs in the wild but can be eliminated as a public health problem in humans, e.g.
- Neonatal tetanus - thousands of children still die of this every year in countries with weaker health care systems and it is easily prevented with a safe and effective vaccine. Neonatal Tetanus
- Meningitis: Defeating Meningitis by 2030
- Hib: Haemophilus influenzae type B
- Yellow fever WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases - Yellow fever this has a reservoir in monkeys but can be eliminated as a public health problem in humans by eradicating the mosquito Aedes aegypti which is the urban vector - and also eradicates Dengue fever which is spread in the same way by the same mosquito.
- Dengue fever Better environmental management for control of dengue in this case there is a vaccine but it has severe limitations, it is most effective with people who have already been exposed to the virus, for those who haven't it can lead to a risk of a more severe version of the disease and sometimes death. Questions and Answers on Dengue Vaccines This is not too surprising since Dengue is a complicated disease with the unusual property that natural immunity to one strain can lead to a more severe reaction to any of the other three strains circulating. Because of the risk of false positives then it's been approved but with major limitations and the risk needs to be communicated to those vaccinated FDA approves the first vaccine for dengue fever, but with major restrictions
- Sleeping sickness. The elimination is well ahead of schedule for the milestones roadmap. Dr Tedros announced on 27th August that sleeping sickness is now eliminated in Togo. 7 other African countries are planning to submit dossiers to show they have eliminated it too. Benin,Cameroon Ghana, Mahli, Rwanda, Uganda,and Equatorial Guinea. A further three have announced their intention to do so, Burkina Faso, Kenya and Chad..
Other diseases we can eradicate as a public health problem include HIV, which kills hundreds of thousands in sub-saharan Africa because of the high cost of the therapeutics which in countries with stronger health care systems can control it for the entire lifetime of the patient, and Hepatitis C.
It’s so far been impossible to develop a good vaccine against HIV because it is so evasive, covered in glycans (sugars) and next to impossible for the immune system to see it.
In 2020 globally, about 680,000 people died of AIDS related illness - many of those preventable with good medicine. Global HIV & AIDS statistics — Fact sheet
However even the big three HIV, Tuberculosis and Malaria, the toughest diseases to vaccinate against ,may eventually fall to the advances in science.
Moderna is starting a trial for an mRNA vaccine against HIV
And the WHO with Biontech are starting an MRNA hub in Africa to make mRNA vaccines for Africa. These are not covered by mRNA patents. They have their eye on a malaria vaccine as well as COVID vaccines.
By 2030 it’s not impossible that many more viruses join smallpox and (soon) polio as extinct diseases that only exist in laboratory samples - or ones that have animal hosts but are stopped whenever they cross to humans.
WITH A GOOD ENOUGH VACCINE - COVID COULD IN FUTURE GET ADDED TO THAT LIST AS AN ELIMINABLE DISEASE - SOME COUNTRIES ALREADY HAVE ANIMAL RESERVOIRS OF COVID - BUT IF THEY RARELY JUMP TO HUMANS - NOT MUCH OF AN ISSUE
We can never eliminate yellow fever as it circulates in wild monkeys. But yellow fever vaccine gives 99% immunity 30 days after vaccination. Also it gets to humans via a particular mosquito and though we can’t eliminate the virus in monkeys we can eradicate the mosquito Aedes aegypti which is the urban vector - and also eradicates Dengue fever which is spread in the same way by the same mosquito. See WHO Report on Global Surveillance of Epidemic-prone Infectiou s Diseases - Yellow fever also Yellow fever
We can never eradicate influenza completely because it has many animal reservoirs. But with a good enough vaccine we could perhaps eliminate influenza almost entirely as a risk in humans, as for yellow fever, eliminating it in humans and then targeting all the situations where it can jump to humans and stopping it fast.
COVID must have an animal reservoir too - possibly wild pangolins - but we haven’t found it yet. The jump over to humans must be very rare.
Although COVID has now infected wild mink and wild US deer, this animal reservoir also doesn’t matter much for humans if it can’t jump back to us easily.
China - and now the US can never become completely COVID free as in, no animal reservoirs. But with a good enough vaccine, it could be effectively COVID free for humans, with only imported cases, if it almost never jumps from pangolins or deer to humans.
But we don’t need to achieve countries with COVID free status to end the acute stage of the pandemic and end the global health emergency.
COVID has now jumped to many species including big cats, a gorilla, minks, white tailed deer, the list so far as of writing this:
- Pet ferret
- Snow leopard
- White-tailed deer
- Fishing cat
Many of those are in zoos but it could spread to the species in the wild and it is present in wild mink and deer.
Then it’s presumably still present in its original animal host in China too.
However ... the only examples of it jumping from animals to humans are in the mink farms.
China hasn’t had a single outbreak due to COVID jumping over again from an animal reservoir. All its outbreaks are traced back to imported cases. Perhaps like MERS it can only jump every few years.
We can put precautions in place to contain it, if it has limited opportunities to jump to humans. Especially if we have a vaccine that is 95% effective at stopping transmission - then it is feasible to eliminate it in humans.
EVEN BEFORE VACCINES, A LARGE FRACTION OF THE WORLD'S POPULATION KEPT COVID OUT - SO IT'S NOT ONLY ELIMINABLE FROM REGIONS IN THEORY - IT'S BEEN ACHIEVED IN PRACTICE
This has to be possible, because - even before vaccines, China, Taiwan, Bhutan, and Tonga have kept it out, they get outbreaks but they are able to end them all. No country has ever achieved that with flu.
With a good enough vaccine next year there is no reason why they ever need to have COVID endemic.
Before COVID, what China did was thought to be impossible - but they show it can be done - and not just for an island, a big country with a very extensive land border can keep a virus out. I hope none of my readers still believe that China has raging outbreaks of COVID that it is ignoring. It’s pretty clear to everyone it really did keep it out.
So it can be done but it needs an all of government, all of society approach that other countries like Vietnam did manage to keep up for a long time, also New Zealand - they could keep out ancestral COVID but Delta proved to be too hard for them. Let’s hope the remaining COVID free countries are able to keep Omicron out.
Very fast detection of Omicron gives us a breathing space to prepare
China, Hong Kong, Taiwan, Tonga and Bhutan (and probably North Korea) have all kept out Delta and may be able to keep out Omicron indefinitely
Others can delay it
So, it's possible that China remains COVID free all the way until enough of the population is boosted with an effective enough vaccine so that it can never become endemic in China.
If we reach that point where it has never become endemic in China, Taiwan, and perhaps Bhutan, Tonga and North Korea with those countries all protected by vaccination rather than travel restrictions - then that's similar to the situation with measles or polio.
From that point on, one country after another can become COVID free. If we eventually do that for all countries, we eliminate it in humans.
YES AN AIRBORNE DISEASE CAN BE ERADICABLE WITH A GOOD ENOUGH VACCINE - WORLD HEALTH ASSEMBLY AIM TO ERADICATE MEASLES WHICH IS AIRBORNE AND VERY CONTAGIOUS
Measles is an airborne disease. But its vaccine is so effective it’s classified as an eradicable disease. If we could vaccinate enough people against measles it would soon be gone.
Measles is airborne and far more transmissible than COVID and has been eliminated locally in both north and south America and is classified as an eradicable disease (not just eliminable because it has no animal reservoir and has an effective vaccine that could eradicate it if enough people got vaccinated). Indeed that is the aim of the WHO and the member states of all six WHO regions.
In 2010, an expert advisory panel convened by the WHO concluded that measles can and should be eradicated The WHO Strategic Advisory Group of Experts (SAGE) on Immunization endorsed these conclusions ] and in 2011, the World Health Assembly (WHA) Executive Board endorsed the SAGE recommendations.
In 2012, the WHA endorsed the Global Vaccine Action Plan, which included targets to achieve existing disease eradication and elimination goals for polio, neonatal tetanus, measles, and rubella by 2020. Among these targets was the objective of regional elimination of measles in 5 of the 6 WHO regions by 2020.
By 2013, member states of all 6 WHO regions had voted for regional elimination target dates on or before 2020, securing the political commitment of all countries.
COVID IS NOT ERADICABLE BECAUSE IT’S FOUND IN ANIMAL HOSTS - BUT IT COULD BE ELIMINABLE IF WE GET A GOOD ENOUGH VACCINE IN 2022
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We don’t eradicate it entirely, not likely we do that because it’s going to linger in animal hosts but we can get to the situation similar to MERS where it almost never occurs in humans and when you get an outbreak it is quickly stopped.
Indeed if we have an effective enough vaccine, and vaccinate all the most vulnerable - which by then might only be mink farm workers, then it would be more like bird flu than MERS, where it jumps to humans sometimes but rarely spreads to anyone else. Also depending on the therapeutics it may be very rare there are any deaths even for those who it jumps to originally.
We will see what happens. It depends on the vaccine.
COVID can never go in that list of
- “Diseases that could be completely eradicated”
But with a good enough vaccine it can certainly go into the list of
- “Diseases that can be eliminated as a public health problem in humans”
Whether we actually eliminate it as a public health problem will depend on what we do.
But with a good enough vaccine, COVID will join many other diseases like yellow fever, Hib, meningitis, sleeping sickness, etc as one that can in principle at least be eliminated if we so choose and put the effort into it and the public are behind it. Some of those diseases like sleeping sickness are well on the way to elimination already.
Maybe some day we can eliminate COVID too.