This week marks one year since the World woke up to the fact that we were on the brink of a global pandemic due to a novel coronavirus coming out of China. The media were full of questions, where did it come from, how does it spread, is everyone going to get sick and die? All very good questions to which we now know a lot of the answers; probably bats, large droplets, some of those with risk factors e.g. old age, obesity, hypertension etc. and yes it is a global disaster with 99.8 million cases and 2.14 million deaths worldwide; the USA being hardest hit, 25.3 million cases and 421,000 deaths, over 6 times the number of cases and 4 times as many deaths compared to the UK 3.67 million cases and 98,530 deaths… UK deaths are over 100,000 now (how quickly my blogs date!)
The scientific press had other questions as well, and one of the most important was “will this virus cause repeat infections?” They were looking at this from the perspective of immunity. Experience from previous novel coronavirus infections such as the original SARS and MERS suggested that antibody levels waned over time, and it was known that at least 4 species of coronavirus regularly circulated within the human population causing “the common cold”. So, the worry is that people can get coronaviruses more than once… a scary prospect.
A recent report from Public Health England’s SARS-CoV2 Immunity and Reinfection Evaluation (SIREN) Study has shown that a small number of people have already had Covid-19 twice (44 out of 6,614 people), and their conclusion has been that immunity following infection only provides up to 5 months protection in 83% of people; but that it is not known how long this protection will last after this. They also noted that past infection doesn’t prevent carriage of the virus and therefore further spread of SARS CoV2 is possible.
This is disappointing but it does prove two things:
WHOA!!! What about the vaccine? Well that “should be different” and hopefully this will give sustained immunity, but there is no long-term data to back this up… REMEMBER Pfizer were first with a vaccine and their next data point in their “ongoing clinical trial” is February 2021.
So why is this happening? Why do people get the infection twice? What might this mean for both natural and vaccine induced immunity and the future of the pandemic? Is there another possible explanation for this phenomenon other than waning immunity? Wouldn’t it be concerning if coronaviruses can evolve to overcome immunity?!? NO! STOP IT!!!
We know that all RNA viruses mutate over time, in fact it is the basis of Darwin’s natural selection whereby new traits that provide a “selective advantage” will continue in a population. Some viruses like Influenza Virus do this all the time in a process called “antigenic drift” where they slowly evolve over time to escape immunity; this is why we need new flu vaccines every year. On the other hand, some viruses don’t evolve much at all e.g. Measles Virus, where any mutation that affects immunity tends to be terminal for the Measles Virus itself; this is the reason the measles vaccine is very effective at giving long-term immunity.
But what about SARS CoV2? Mutation does occur but fortunately it appears to happen slowly, much slower than for most RNA viruses, because SARS CoV2 has an effective RNA polymerase that corrects errors. As a result, it is thought that the SARS CoV2 genome of 30,000 bases only changes by about 20 bases a year…
But we know it does change because we are seeing new variants in the UK, South Africa and Brazil, which have changed “enough” to start causing concerns about spread and immunity. How likely are these new variants to matter? That’s the question a group from Seattle, USA, have been investigating… and the answer is a bit scary!
A scary research paper from Seattle
I think this study from Seattle published at the end of last year is one of the best and most important pieces of research about coronaviruses I have read; and the results have implications for the current Covid-19 pandemic. When you think about it even the title sounds scary – a human coronavirus evolves antigenically to escape antibody immunity. Aren’t they cheery souls!
The researchers looked at one of the common cold coronaviruses known as 229E (isn’t that a new Star Wars droid, like R2D2?)… 229E is like the SARS CoV2 virus. It is known to circulate all the time within the human population. So they decided to extrapolate their “known” results to the current pandemic. So, what did they do?
They started by collecting 229E spike protein sequences from genetic databases and then genetically modified lentiviruses which they could study in a lab to express the spike proteins… rather than making a “new coronavirus” which has the potential to cause another pandemic!!! (Don’t get me started on the China bashing laboratory released conspiracy theorists! Just phooey). This would then allow them to test whether antibodies could neutralise the new lentiviruses by the antibody’s ability to bind to the artificially created spike protein. They chose spike protein sequences and created artificial viruses that represented 229E when it was circulating in 1984, 1992, 2001, 2008 and 2016.
Next the researchers collected serum samples from a “serum bank” and screened them for antibodies against the spike protein that occurred most recently BEFORE the serum was collected. For example, a serum from 1985 would be tested against the virus from 1984, serum from 1998 would be tested against the virus from 1992, etc. They also collected sera from children born after 2016.
The clever bit of the study is when they tested all of the sera they had collected against all of the viruses from the different years. The idea was to see if old sera contained antibodies capable of neutralising FUTURE viruses that hadn’t evolved yet. If sera from the past were capable of neutralising virus from the future then the virus wasn’t evolving it’s spike protein to escape the immunity; if sera from the past couldn’t neutralise the virus from the future then the virus had evolved it’s spike protein to escape immunity… simple and brilliant!
What did they find?
This is the scary bit. The results of the study were clear; antibody in serum was capable of neutralising ALL of the viruses that had come before but most could NOT neutralise those that came after the serum had been collected. Think of it as your Microsoft Word doc; you can open “.doc” files on the old word 97 software but not the new 2007 XML-based file format “.docx”, but new versions of the software can open both file types. They found that their “229E coronavirus” mutates its spike protein over time in a way that overcomes previous immunity. In other words, the virus is capable of evolving itself to cause repeat infections. This may be why the same 4 types of coronavirus continue to cause common colds.
This is scary because the implication is that SARS CoV2 can do the same; it can evolve to escape immune recognition by antibodies against the spike protein making long-term immunity less effective whether it is naturally acquired, or vaccine induced. This would mean that whatever we do SARS CoV2 isn’t going to go away! ARGH!!
BUT before you run off screaming there are 2 really important factors that mean this may not be as bad as it first appears!
Firstly, the study didn’t account for the evolution of the immune response over time, just the evolution of the virus. It is very likely that continued and repeat exposure to “229E coronavirus” every year will ALSO cause the immune system to evolve in response to small mutations in the spike protein over the same time. Even though the antibodies against the spike protein may not be perfect, they are likely to be “good enough” to prevent severe disease. This would explain why 229E just causes the “common cold” rather than debilitating us all with a severe respiratory infection. It is expected that the same will eventually happen with SARS CoV2 once enough of us have been infected or vaccinated. The continued adaptation of our immune systems after the initial insult will protect us from getting really sick in the future.
Secondly, even if our immune systems don’t adapt fast enough to the changing spike protein, the new ways of producing vaccines make them adaptable and as they have already been “approved in principle” it is easier to modify current vaccines against future variants of SARS CoV2 and this could be produced at very short notice e.g. Pfizer say they can change their Covid-19 vaccine within 6 weeks!
So, there it is. It turns out that other coronaviruses do show “antigenic drift” and evolve to escape immunity over time, much like influenza viruses, and this is probably likely to occur in SARS CoV2. BUT what always accompanies “antigenic drift” in all good microbiology textbooks? “Antigenic shift”!!! Influenza Virus uses both shift and drift; antigenic shift is the way that it genetically recombines to create new viruses and why we have always been worried about flu pandemics occurring. I suspect this is one of the main reasons that the WHO are in China looking for the source of SARS CoV2; they want to be sure it hasn’t “antigenically shifted” e.g. a bat coronavirus and a different pig coronavirus have recombined to create a novel coronavirus, neither bat nor pig but human! Just targeted at us!
So far there is no evidence that coronaviruses are able to “antigenically shift” and produce an entirely new virus… at least so far… don’t have nightmares…!
A recent report from Public Health England’s SARS-CoV2 Immunity and Reinfection Evaluation (SIREN) Study has shown that a small number of people have already had Covid-19 twice (44 out of 6,614 people), and their conclusion has been that immunity following infection only provides up to 5 months protection in 83% of people; but that it is not known how long this protection will last after this. They also noted that past infection doesn’t prevent carriage of the virus and therefore further spread of SARS CoV2 is possible.
This is disappointing but it does prove two things:
- You must continue to follow infection control precautions even if you have previously been infected; to protect yourself and others
- Natural infection will not provide sufficient herd immunity to protect the population
WHOA!!! What about the vaccine? Well that “should be different” and hopefully this will give sustained immunity, but there is no long-term data to back this up… REMEMBER Pfizer were first with a vaccine and their next data point in their “ongoing clinical trial” is February 2021.
So why is this happening? Why do people get the infection twice? What might this mean for both natural and vaccine induced immunity and the future of the pandemic? Is there another possible explanation for this phenomenon other than waning immunity? Wouldn’t it be concerning if coronaviruses can evolve to overcome immunity?!? NO! STOP IT!!!
We know that all RNA viruses mutate over time, in fact it is the basis of Darwin’s natural selection whereby new traits that provide a “selective advantage” will continue in a population. Some viruses like Influenza Virus do this all the time in a process called “antigenic drift” where they slowly evolve over time to escape immunity; this is why we need new flu vaccines every year. On the other hand, some viruses don’t evolve much at all e.g. Measles Virus, where any mutation that affects immunity tends to be terminal for the Measles Virus itself; this is the reason the measles vaccine is very effective at giving long-term immunity.
But what about SARS CoV2? Mutation does occur but fortunately it appears to happen slowly, much slower than for most RNA viruses, because SARS CoV2 has an effective RNA polymerase that corrects errors. As a result, it is thought that the SARS CoV2 genome of 30,000 bases only changes by about 20 bases a year…
But we know it does change because we are seeing new variants in the UK, South Africa and Brazil, which have changed “enough” to start causing concerns about spread and immunity. How likely are these new variants to matter? That’s the question a group from Seattle, USA, have been investigating… and the answer is a bit scary!
A scary research paper from Seattle
I think this study from Seattle published at the end of last year is one of the best and most important pieces of research about coronaviruses I have read; and the results have implications for the current Covid-19 pandemic. When you think about it even the title sounds scary – a human coronavirus evolves antigenically to escape antibody immunity. Aren’t they cheery souls!
The researchers looked at one of the common cold coronaviruses known as 229E (isn’t that a new Star Wars droid, like R2D2?)… 229E is like the SARS CoV2 virus. It is known to circulate all the time within the human population. So they decided to extrapolate their “known” results to the current pandemic. So, what did they do?
They started by collecting 229E spike protein sequences from genetic databases and then genetically modified lentiviruses which they could study in a lab to express the spike proteins… rather than making a “new coronavirus” which has the potential to cause another pandemic!!! (Don’t get me started on the China bashing laboratory released conspiracy theorists! Just phooey). This would then allow them to test whether antibodies could neutralise the new lentiviruses by the antibody’s ability to bind to the artificially created spike protein. They chose spike protein sequences and created artificial viruses that represented 229E when it was circulating in 1984, 1992, 2001, 2008 and 2016.
Next the researchers collected serum samples from a “serum bank” and screened them for antibodies against the spike protein that occurred most recently BEFORE the serum was collected. For example, a serum from 1985 would be tested against the virus from 1984, serum from 1998 would be tested against the virus from 1992, etc. They also collected sera from children born after 2016.
The clever bit of the study is when they tested all of the sera they had collected against all of the viruses from the different years. The idea was to see if old sera contained antibodies capable of neutralising FUTURE viruses that hadn’t evolved yet. If sera from the past were capable of neutralising virus from the future then the virus wasn’t evolving it’s spike protein to escape the immunity; if sera from the past couldn’t neutralise the virus from the future then the virus had evolved it’s spike protein to escape immunity… simple and brilliant!
What did they find?
This is the scary bit. The results of the study were clear; antibody in serum was capable of neutralising ALL of the viruses that had come before but most could NOT neutralise those that came after the serum had been collected. Think of it as your Microsoft Word doc; you can open “.doc” files on the old word 97 software but not the new 2007 XML-based file format “.docx”, but new versions of the software can open both file types. They found that their “229E coronavirus” mutates its spike protein over time in a way that overcomes previous immunity. In other words, the virus is capable of evolving itself to cause repeat infections. This may be why the same 4 types of coronavirus continue to cause common colds.
This is scary because the implication is that SARS CoV2 can do the same; it can evolve to escape immune recognition by antibodies against the spike protein making long-term immunity less effective whether it is naturally acquired, or vaccine induced. This would mean that whatever we do SARS CoV2 isn’t going to go away! ARGH!!
BUT before you run off screaming there are 2 really important factors that mean this may not be as bad as it first appears!
Firstly, the study didn’t account for the evolution of the immune response over time, just the evolution of the virus. It is very likely that continued and repeat exposure to “229E coronavirus” every year will ALSO cause the immune system to evolve in response to small mutations in the spike protein over the same time. Even though the antibodies against the spike protein may not be perfect, they are likely to be “good enough” to prevent severe disease. This would explain why 229E just causes the “common cold” rather than debilitating us all with a severe respiratory infection. It is expected that the same will eventually happen with SARS CoV2 once enough of us have been infected or vaccinated. The continued adaptation of our immune systems after the initial insult will protect us from getting really sick in the future.
Secondly, even if our immune systems don’t adapt fast enough to the changing spike protein, the new ways of producing vaccines make them adaptable and as they have already been “approved in principle” it is easier to modify current vaccines against future variants of SARS CoV2 and this could be produced at very short notice e.g. Pfizer say they can change their Covid-19 vaccine within 6 weeks!
So, there it is. It turns out that other coronaviruses do show “antigenic drift” and evolve to escape immunity over time, much like influenza viruses, and this is probably likely to occur in SARS CoV2. BUT what always accompanies “antigenic drift” in all good microbiology textbooks? “Antigenic shift”!!! Influenza Virus uses both shift and drift; antigenic shift is the way that it genetically recombines to create new viruses and why we have always been worried about flu pandemics occurring. I suspect this is one of the main reasons that the WHO are in China looking for the source of SARS CoV2; they want to be sure it hasn’t “antigenically shifted” e.g. a bat coronavirus and a different pig coronavirus have recombined to create a novel coronavirus, neither bat nor pig but human! Just targeted at us!
So far there is no evidence that coronaviruses are able to “antigenically shift” and produce an entirely new virus… at least so far… don’t have nightmares…!
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