Things are starting to get complex. So, I updated my very bland vaccine table from December. I hope it’s helpful in keeping track of all the moving parts.
Things are starting to get complex. So, I updated my very bland vaccine table from December. I hope it’s helpful in keeping track of all the moving parts.
Your national epidemiological report (as of Jan 25 7:19PM CST)…
Cases are dropping and they are dropping fast. It looks like we have turned the post-holiday corner. Our 7-day average is now the same as it was in November. Today, 46 states have a decreasing 7-day average of cases and 5 states are plateauing. Not one state has an increasing 7-day average.
Hospitalization trends follow case trends. So, naturally, hospitalizations are looking better too. Hospitalizations in 33 states are decreasing, 16 states are plateauing, and 2 states are increasing (Vermont=27% and Kansas=18%).
Unfortunately, deaths lag hospitalizations. Deaths are still catching up from the holidays. 22 states have decreasing deaths, 18 states are plateauing, and 11 states are increasing. The highest increase in deaths is Arkansas (56%!), closely followed by Hawaii (54%). Yesterday, we had the highest daily death toll of ~4,400 COVID19 deaths in one day. Which is unfathomable. We are predicting 500,000 deaths by mid-February. This would make COVID19 the second leading cause of death in the United States… within 11 months.
We can finally add a new (positive) metric to the report… Vaccinations! 22.7 million doses have been administered. Of which, 3.3M people have received both doses. 41.4 million doses have been distributed. Today, Alaska is the winner with 13,264 per 100K doses administered. West Virginia is a close second with 11,383 per 100K doses administered. North Dakota and Nevada come in 3rd and 4th place. The Western US is, by far, the slowest to administer doses, with CA, NV, and AZ being at the bottom of the bunch. We have yet to gain speed in vaccinations, but this should be coming soon. We are figuring out ways to squeeze a 6th dose out of each vial (by producing special syringes) and deploying mass vaccinations sites. We should get to at LEAST 1 million doses per day in the United States soon. We can’t do this fast enough, as we need to beat the acceleration of the variants.
Every epidemiologist I know is worried about the B.1.1.7 variant (first discovered in the UK). It took 3 months for B.1.1.7 to become the dominant strain in the UK. If this variant continues to spread in the US, we are looking at a March surge that we’ve never seen before. As of tonight, B.1.1.7 is in 23 states with 293 lineage cases reported. But this is among a bias sample of cases. The U.S. ranks 43rd in percentage of cases sequenced. We estimate that B.1.1.7 is ~1% of cases in the United States.
We have 1.5 months to prepare. Early efforts that can limit the spread of the B.1.1.7 variant, such as universal and increased compliance with public health mitigation strategies, will allow more time for ongoing vaccination to achieve higher population-level immunity.
Case, hospitalization, and death data: COVID19 tracking project
CDC variant/immunization rates in regards to infections: https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm…
Variant cases in the US: https://www.cdc.gov/…/transmission/variant-cases.html
If you remember, the South Africa variant (better known as 501v2), Brazil variant (better known as B1.1.28/501.V3), and the UK variant (better known as B1.1.7/501Y.V1) have all recently grabbed the attention of scientists because each have mutations on the spike protein. These are important to investigate because the spike is the keys to our cells. In other words, the virus can mutate to make a smarter key.
There are two new pieces of information this week/today.
First, the 501v2 (South Africa) variant…
-What happened? On Jan 20, a preprint came out from Rockefeller University. They took the antibodies of 20 volunteers who received an mRNA vaccine and mixed it with viruses containing the mutations. This experiment, called an antibody neutralization assay, enables the researchers to determine whether vaccine-induced antibodies will be effective against the new variants of virus circulating globally.
-What did they find? The antibodies effectiveness against the mutations was reduced by a small (but statistically significant) degree (ranged from a 1- to 3-fold reduction).
-What does this mean? The vaccine is working against 501v2 (thanks to the polyclonal response), but these mutations *may* impact the efficacy of the vaccine. We need more “real-world” studies, in addition to the well-controlled, test-tube studies.
Second, the B.1.1.7 (UK) variant…
-What happened? Today, NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group) met to discuss new studies on B.1.1.7. They previously reported a study in which there was no increase in death due to the new variant. However, with more time comes more data.
-What did they report? There are three new studies (one by The London School of Hygiene & Tropical Medicine, one by Imperial College London, and one by University of Exeter) that all showed that the B.1.1.7 is more deadly by about 1.65 fold.
-What does this mean? “There is a realistic possibility that B.1.1.7 is associated with an increased risk of death compared to the virus without these mutations.” While the risk of death remains low, this does increase it by a significant amount. There is a limitation to these studies… Only 10% of COVID19 deaths have their virus coded to know which mutation the person had. In other words, this could be a bias sample. Deaths are lagged from cases, so the more time goes by, the more and more accurate of a picture we will get.
Bottom line: The virus is getting smarter. Slowly but surely. This underscores the need to vaccinate as many people as quickly as we can, because these mutations are signals of antigenic drift.
Rockefeller study: https://www.biorxiv.org/…/2021.01.15.426911v1.full.pdf
NERVTAG meeting minutes: https://assets.publishing.service.gov.uk/…/NERVTAG…
I knew the SA story was coming out at some point this week, so I prepared with two brilliant colleagues, Dr. Jessica Steier (public health scientist) and Dr. Andrea Love (immunologist). They are both doing wonderful work at The Unbiased Science Podcast (www.unbiasedscipod.com).
The Moderna and Pfizer vaccine induces something called a polyclonal response. Basically, the vaccine instructs the body to generate numerous shaped antibodies that can connect to many different parts of the virus (see picture). Those antibodies are diverse in shape and cover the whole waterfront of the spike protein.
A spike protein mutation here and there would still leave areas for the antibodies to attach. Mutations to those target sites raise the possibility that the vaccines would be less effective, not necessary that they won’t work at all. Mutations are likely a long way from making any vaccine useless. Scientists say it will probably take years.
However, if a random mutation did render a vaccine useless, the mRNA instructions are incredibly easy to change. This is the beauty of this type of vaccine. It’s like editing a Word document; just tweaking the code a little. And, the FDA wouldn’t need Phase I-III trials again. This is because the code isn’t changed enough to concern safety or efficacy. They would just need to see a study with a few dozen people that showed the new code produced satisfactory amounts of antibodies and protection against the mutated virus.
According to GISAID (a public genetic database of the virus) there’s about 12,000 known mutations for the COVID-19 virus. And the mutations in a few (UK, SA, Brazil, and Nigerian variants) look like they change some of the target sites, but certainly not all.
We are still very much hopeful for the effectiveness of the vaccines.
Some data sources for more reading:
WHO 12,000: https://www.who.int/publications/m/item/weekly-epidemiological-update—5-january-2021
Several COVID19 developments popped up in the past 24 hours. Here’s my attempt to keep you up to speed…
-Data are stabilizing and we are starting to see the impact of the holidays. For the second day in a row the United States had more than 4,000 deaths per DAY. This is about what we, epidemiologists, expected because 22 days ago there were 239,795 daily cases. Today, 131,889 people are hospitalized and 7,900 people are on ventilators. We are hitting new records across every metric.
-There is NO scientific evidence of a new US variant (this is different than the UK or SA variant). This misinformation stemmed from a document circulated yesterday that speculated the increase in winter cases (compare to summer) must be due to a new variant. In Nov and Dec, 5,700 samples were collected and analyzed by the CDC and there is no evidence of this. However, the more this thing spreads, the more opportunity this virus has to mutate. Can we agree to start wearing masks and stop seeing friends?
-The Biden administration announced that they will not withhold the second dose. This is still a highly debated topic in public health (maybe the most debated since the pandemic began). My scientific opinion: Supply isn’t our issue right now; capacity and logistics are. As of this morning 22.1 million vaccines have been sent off; only 6.68 million Americans received their first dose. Yes, some of this discrepancy may be due to reporting lags, but this doesn’t explain it all. Our federal priorities should be setting up vaccine surveillance, setting up mass vaccination sites, and clear, consistent communication. Way too many people are in the dark. Now, if we get off the ground from this rocky start, then we can talk about the second dose.
-Every Friday the CDC Vaccine Adverse Event Reporting System (VAERS) is updated. The more people that get vaccinated, the closer we get to the “true” rate of adverse events. 6.68 million doses of the vaccine have been distributed and 3,907 adverse events have been reported to VAERS. The most common symptom is headache, nausea, and pain. 30 people/physicians reported anaphylactic reactions. On Jan 6, CDC published a report describing 21 of these cases in 1.89 million doses. Of which, 71% occurred within 15 minutes of vaccination. There are limitations to VAERS data (which I’ve posted about before).
Okay, I think that’s it for now.
Graph 1: Covid Tracking Project
Graph 2: Made by yours truly with VAERS data
Vaccine tracker: https://covid.cdc.gov/covid-data-tracker/#vaccinations
CDC report: https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm
I would like to preface by taking one step back… COVID19 is just not mutating very quickly. Overall, the virus circulating today looks relatively similar to the one that appeared in late 2019. This is because when COVID19 copies itself, it uses a proofreading system to catch errors. The COVID19 virus is proofreading itself much more than, say, the flu. The flu virus is constantly changing; we have to create a new flu vaccine every year. The measles virus is on the other side of the spectrum; it hasn’t changed since we discovered it in the 1960s. COVID19 is somewhere in between. This is important context to keep in mind.
With that said, the virus is changing. This is normal. The South Africa (SA) variant has recently grabbed the attention of scientists. Like the UK variant, the SA variant has a few mutations on the spike protein. It’s particularly important to look at these because the virus spike is the key to opening the doors on our organ’s cells (called ACE2 receptors). We want to know whether the virus is making smarter keys; just like we are making smarter locks (vaccines).
Of the several changes on the spike, there is one in particular (called E484K) we are looking closely at for two reasons:
1) E484K mutation has been shown to reduce antibody recognition IN THE LAB. As such, the virus goes “incognito” and antibodies tend to not recognize it. It’s not clear yet whether the COVID19 E484K mutation tricks antibodies triggered by current vaccinations.
2) It’s a bit more difficult to track compared to the UK variant that’s easily detectable on a PCR test.
Thus far, the SA variant has spread to other countries including Austria, Norway, Japan, UK, Finland, Australia, Zambia, France, and most recently South Korea.
There is currently no evidence that this variant causes more severe illness or that a vaccine wouldn’t protect us.
IF it did trick vaccines (and that’s a big if), vaccine formulas can be changed very quickly (in a matter of 4-6 weeks). Pfizer and Moderna are testing the SA variant now and will let us know soon.
My scientific opinion:
We now know that the new variant was first found on Sept 20, 2020 in Kent and another on Sept 21, 2020 in Greater London. The new variant spread undetected until early December 2020. It’s now been identified in several countries, including several states, however spread is likely all over. The US (and rest of the world) doesn’t have nearly the variant surveillance that the UK does. (This is likely why the variant was first detected in the UK).
In the UK, the body that considers new evidence about the virus is called the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG). They virtually met on Dec 18 and Dec 22. During these meetings, there were 3 independent analyses presented regarding transmissibility (one done by University of Edinburgh; one by Imperial College London; one by London School of Hygiene and Tropical Medicine). In short, all three analyses agreed that the new variant is somewhere between 56%-71% more transmissible compared to other variants. The R(t) is estimated to be 1.2 (which is 0.38 higher than other variants). “The committee therefore has high confidence that the new variant can spread faster than other variants currently circulating in the UK”.
In one of these preliminary analyses (by Imperial College), data suggested that there may be an increase in transmission in children aged <15 years. In the meeting minutes, this is followed in bold type by: “However, these data are preliminary, and more work is required before any firm conclusions can be reached”. The primary author of this analysis, Prof Neil Ferguson, followed up this statement saying, “We haven’t established any sort of causality on that, but we can see it in the data. We will need to gather more data to see how it behaves going forward.”
This preliminary analysis was followed by a London hospital worker (Ms Laura Duffel) stated “having a ward full of children with coronavirus”. The combination of these two events have sparked quite the concern. Ms Duffel’s claim was quickly denied by clinicians. The Royal College of Paediatrics and Child Health (RCPCH) said children’s wards are not seeing any “significant pressure” from Covid-19.
In addition, members of COVID-19 Genomics UK (COG-UK) said they are not familiar with any data to suggest kids have more transmissibility than adults. COG-UK has examined the genetics of more than 160,000 cases of coronavirus in the UK and is constantly watching how the virus evolves to see whether any of the mutations are important. They said there is more data is needed to make any comments on how it affects specific groups.
So, in short, we need more data (story of our life). Making sweeping policy changes, like closing schools, is still unfounded in the US (in my humble opinion). We will see what the UK (and other countries) decide regarding schools soon.
More meeting minutes on the three analyses: https://m.box.com/shared_item/https%3A%2F%2Fapp.box.com%2Fs%2F3lkcbxepqixkg4mv640dpvvg978ixjtf/view/756964987830
The UK COVID19 variant (called VOC 202012/01) has 17 mutations, among which eight are located in the spike protein (the key which unlocks our cells for infection). At least three mutations have the potential to change the game.
A few days ago, scientists from the Center for Mathematical Modeling of Infectious Diseases came out with the first (and only) study on the new UK variant. The scientists were able to get this out quick because this study is considered a “social” epidemiological study. In short, they used data from hospitals, seroprevalence, and mobile phones to model mathematical equations.
They found that the new variant is spreading faster. In fact, it’s 56% more transmissible than previous variants. They were able to use the equations to know that the increase is NOT due to increased social interactions. This suggests that, wherever this variant is, there will be an onslaught of cases. The epidemiological curve in Wales is something we can expect. The good news is that the variant doesn’t lead to a higher rate of severe disease (ie symptoms or death). In other words, if you get infected by this variant, the likelihood of ending up in the hospital or dying is the same as other variants.
The scientists were very clear that current public health measures won’t stop its spread. The R(0) is too high. They suggested that schools need to be closed until February. Especially since it seems that this new variant is highly transmissible among kids (this is where the hot spots of the new variant seem to be coming from). Also, they called for more urgent vaccination campaigns. We aren’t vaccinating quick enough.
We aren’t sure if this new variant is in the United States. However, we would be surprised if it wasn’t, considering the incredible global reach of COVID19. Anything we do now (like cancelling flights) is likely way too late.
This study starts painting a very important picture of the new variant. We are still waiting on “biological” studies to point us to the exact mutation that’s causing this, so we can learn more. In the meantime, stay vigilant and get your vaccine.
Yes, there is another variant in the UK that MAY be increasing transmissibility. Cases are increasing at exponential rate in Wales. But there are a few things to keep in mind…
To mutate and change is what viruses do. Most of the time it’s a meaningless tweak. Sometimes the virus gets worse at infecting us and the new variant just dies out.
Sometimes the virus just gets lucky, in that a new variant hits the right people at the right time. This happened in Spain during the summer. Headlines called it the the “Spanish strain”, but the exponential cases was explained by simply people catching it on vacation and bringing it home. It wasn’t due to the new variant. It’s important to keep in mind that the virus spreads with political and social contexts in the background. The UK may be placing the blame of new Christmas shutdowns on science, rather than taking the blame of soaring cases due to lax policies.
Sometimes, though, viruses do find a new winning formula. But, we honestly don’t have the data yet to know the full picture. The World Health Organization is working on it. It will take laboratory experiments to figure out if this variant really is a better spreader than all the others.
Will this impact the effectiveness of the vaccine? Probably not. It takes a collection of mutations to impact vaccines. Vaccines are made with mutations in mind. This UK variant has a mutation on the spike protein of the virus. It’s not the first time we’ve seen a mutation on the spike protein. This gains the attention of scientists, though, because the spike is the virus’s key to unlock the door into our cells. Any changes made to that key can make it easier for the virus to get inside. This mutation is certainly something to keep an eye on.
As one professor (McNally) said: “We know there’s a variant, we know nothing about what that means biologically…It is far too early to make any inference on how important this may or may not be.”
So, in the meantime, everyone take a big, deep breath. Including those in charge of news headlines. Keep doing what you’re doing. This has no implications (yet) on how we should change behavior. Keep washing those hands, keeping your distance, and wearing masks.