We are scientists studying how COVID-19 affects your immune system! We're part of the UK Coronavirus Immunology Consortium (UK-CIC), a UK-wide collaborative research project. As us anything!

It's been over a year since people first started getting COVID, do we know now how long those people might be immune for? Or how often people get reinfected?

Very interesting question Ms-Piggy. There are a few studies that have looked at how long our immune response to COVID-19 lasts. I would like to answer your question in 2 parts

Natural infection - One study looked at people who were naturally infected with COVID-19 and found that they could still find immune cells that can fight COVID-19 8 months after infection. This would suggest that we are protected at least up to 8 months after infection. Other studies are following these recovered COVID-19 patients for a much longer time and we expect the results from these studies soon.

Vaccine responses - The clinical trials for the vaccines release interim data which showed efficacy of the vaccines within a time period. There are plans to follow these volunteers on for a while to answer the questions you have raised regarding how durable the immune response is. In the real-world setting with vaccination, we only started vaccination in December 2020 and so its too soon to tell, however we expect that vaccine induced responses should last for as long, if not longer than those from natural infection.

Regarding re-infection - This is hard to say at the moment and would depend on how well a person mounts an immune response after infection or vaccination, the ability of the antibodies to disarm (neutralise) the new variant and how long our immune responses after infection or vaccination lasts. The easiest way we can prevent re-infections is by stopping transmission and thus preventing viral mutation. The most certain way to do that at the moment is by getting vaccinated

Ane

What are the biggest things we still don't know about Covid 19?

Hi Knute, this is a great questions so all 3 researchers are going to have a go I think.

For me the biggest unknown is what is the immune correlate of protection against SARS-CoV-2 infection. What we mean by correlate of protection is the one (or several) parameters we can measure to say 'yes that person has an immune response which is highly likely to stop them from getting infected and getting ill even if they were exposed to sars-cov-2'. For instance, for hepatitis B, my other area of interest, when you're vaccinated we can measure the antibodies in your blood and say yes this person is likely to be protected. We don't yet know what that is for SARS-CoV-2. So we know vaccinated people are less likely to get infected and we can measure their antibodies and other immune parameters but we can't put a number on what is enough yet. So we can't identify who is still vunerable etc, who needs a boost vaccine, we can't optimise vaccines as easily. It could tell us also how long vaccine protection last etc. It is often the immune system as a whole that helps protect but sometimes its possible to identify a correlate of protection and thats what we need now I think. - Leo

Hey Knute5,

We thought it would be fun for each of us to answer and see how (dis)similar our answers are!

For me there are two big questions:

1) Will the virus evolve to evade the vaccines? - Unfortunately only time will give us the answer to that one.

2) What causes some people to have life-threatening disease and others to have asymptomatic infection? Can we suppress severe disease? - Some big strides have already been made in preventing fatal disease, and case-fatalities have fallen quite a bit as we learn which drugs work. However, I think we'll see our understanding of this disease improve to the extent that we can target even better drugs to limit disease severity.

- Ryan

Thanks Knute5. I like this question especially because it gives us a chance to look at the fears surrounding COVID-19 and the vaccines.

One of the biggest unknowns would be how long the immune response to COVID-19 - after infection or vaccination - would last. This is a very important question but one that we do not know the answer to yet. One study that looked at people 8 months after infection found potent immune responses at this time so we expect vaccine responses to be just as long if not longer.

Re-infection with mutant COVID-19 is another unknown. Thankfully SARS-CoV-2 that causes COVID-19 is a relatively stable virus but we have had variants of concern emerge. We can slow this down by vaccination as well as following public healthy guidelines like social distancing and hand-washing. These 2 measures would help to reduce transmission.

Long term safety of the vaccines is another cause for concern for some people but there is constant surveillance and monitoring of the vaccines by regulators so it is important to report side effects. All emergency use licensed COVID-19 vaccine (mRNA and Adenovirus vectors) use platforms that have been tried in other disease scenarios as well as in COVID-19 and deemed safe

Ane

Do you guys have any idea why multi-organ failure is so common in critical Covid cases? I’m a new nurse in critical care and I haven’t been able to get a very clear answer. My first thought was hypoxemia but I’ve seen it in patients with normal oxygen saturation too

Hey! Firstly, thank you for the work you do - as Immunologists we work closely with all sorts of clinical staff and know what a hectic/intense/crazy year you have all experienced.

In Immunology we often talk about 'mechanisms', meaning the immune reaction that triggers a response. The mechanism(s) behind multi-organ failure in respiratory infections (including and beyond Covid) aren't completely understood. Certainly hypoxia can cause tissue damage to non-respiratory organs and this presents one likely mechanism, but the immune response itself might be at least as important in causing organ damage. We know that in patients with severe disease the immune response goes beyond it's helpful role in clearing the virus and actually starts driving some of the symptoms and progression of the disease. This has been termed a 'cytokine storm' by some, but (in my opinion) that's a bit of an exaggeration. It seems that some aspects of the immune response are over active, or don't switch off properly when they've done their job in tackling the virus. This causes inflammatory responses that perpetuate themselves and start damaging the organs. To tackle that, some anti-inflammatory therapies have been shown to limit disease severity/prevent mortality e.g. the steroid Dexamethasone and an anti-inflammatory antibody therapy called Tocilizumab - both suppress different bits of the immune response, and this seems to benefit the patients, supporting the idea that the immune response itself at least partially causes the disease. - Ryan

I live with someone who is afraid to get the vaccine because "it was rushed out". Any advice on how I can help them feel safer to get vaccinated?

Hello, I can understand the concerns but be rest assured that none of the vaccines were rushed and safety was never compromised.

In fact in this study published in 2018 they very clearly talk about the mRNA technology and some studies where it had been used in and plans for future studies https://www.nature.com/articles/nrd.2017.243 . The reason we saw it used for COVID-19 first is because everything else stopped because of the pandemic. There are currently plans to use the technology for Flu and HIV vaccine clinical trials. The adenovirus vectored vaccines have been in development of several years for Flu, MERS, EBOLA, Malaria and has we had a chance to optimised it from what we learnt in those trials. I worked on one of such studies in 2016.

The success of the covid-19 vaccines is a true testament to the hard work of lots of researchers who have been working through the years on this from Barney Graham, Jason Maclellan, Katalin Kariko, Drew Weissmann, Sarah Gilbert and Tess Lambe to all other scientists all over the world. not only have we been working for years on these technologies, but we also dropped everything else and all hands focused on getting COVID-19 vaccines out. Labs were running 24 hours a day and 7 days a week for months. This all facilitated the world.

Finally, because of the large scale devastation the pandemic was causing, we had an injection of funds like no other from the government and funding organisations. we had great collaboration between the government, industry partners, funding bodies and academics. and we were allowed to run our clinical trials in parallel to each other rather than sequentially. The regulators also worked tirelessly to remove red tapes to get the vaccine to the world

Your friend can be rest assured that in all this, safety and having an efficient vaccine was our top priority. We did not compromise on this

Ane

I think this is a good quick video: https://www.youtube.com/watch?v=ddDiyIKUP0M

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No steps were skipped in the development of any of the vaccines compared to any other drug or vaccine. Things were just done as quick as possible by regulators working overtime, and each stage being planned in advance hoping the vaccines would pass the previous one - whereas usually you would not gamble on setting up the next stage until you were sure it was shown to be safe in small number of people and then effective. Its just because this was an unprecedented problem with everyones attention and the funding to do everything as quick as possible, not that any stages were skipped.

Most of the vaccines now in use have actually gone through more rigorous testing and been administered to more people than many previously licensed vaccines already and we are super lucky that they have been shown to be safe and effective.

- Leo

Hi, Thanks for AMA!

One of my relative cought covid and her oxygen level was dropping. She is 53 years old. It has been one month since she is hospitalised still her oxygen is dropping without support. Doctors are saying it's no longer due to covid, it's due to secondary infections. My question is, what causes secondary infections and is there any prevention for it? It would be helpful if you explain other complications that one might face during treatment and posts covid. Thanks.

Hey, I'm very sorry to hear about your relative, I do hope that they recover fully soon.

Secondary infections are fairly common after a severe respiratory viral infection, particularly if you needed some kind of breathing/oxygen support. These are usually caused by bacteria that we call 'opportunistic pathogens', meaning that these kinds of bacteria usually don't cause infections by themselves but when the lungs are damaged (e.g. by the viral infection) they start replicating and spreading around the airways. These kinds of secondary infections are usually treated with antibiotics but this isn't always successful, or might take some time to have an effect. This may be because the bacteria are resistant to antibiotics, or because only quite low concentrations of antibiotics make it into the lung and help combat the infection. - Ryan

Is there any evidence that mixing vaccines between the first and second dose would be better than receiving two doses of the same vaccine?

Hi,

This is a really interesting area, not just for SARS-CoV-2 but for vaccines against many infections. Normally you would do small trials of 5-10 people to see which combinations work best, the best time to wait between giving 1st and 2nd vaccines, best dose etc. and then scale up. What was easiest to do at the start was for companies to use info they already had about using their vaccine platform/type of vaccine in a prime-boost. But people are trying combinations now:

Here is a link to a trial being done in Oxford (maybe Ane is even working on this ;) ) where they are looking at different combinations https://comcovstudy.org.uk/participate-comcov2

Theres actually a lot of data from vaccine development for HIV, HCV (my area of research) suggesting mixing different types of vaccine as they all have different strengths and can complement each other. There is no evidence to suggest it would be a bad thing to mix.

We are extremely lucky to have several vaccines that work well so we are spoiled for choice and the more we test the more we can optimise the vaccines we have, making them work better and offer protection for longer hopefully!

- Leo

Thanks for all the work you do.

What preventative measures are you personally taking with regard to COVID-19?
Vitamin D? Nasal sprays? Any particular kind of mask? Avoiding certain situations?

Hey,

I've been lucky enough to have my vaccines already, so hopefully my immune system will help me out if I do encounter the virus in the future. Otherwise, I'm still not meeting with people indoors, so if I go to see friends it's only outdoors (the exception to this is work, where meeting indoors is essential in which case we wear masks e.g. in shared offices). Straightforward 3-ply 'surgical' masks seem to be pretty effective so anything more complicated might not be necessary. Then things like regular handwashing, not shaking hands, going on public transport in quieter hours are all sensible. -Ryan

Do you believe Vitamin D3/B12 Deficiancy plays a role in how our bodies react to Covid 19?

Hi Odd-Worry, I think the role of Vitamin D3/B12 in the immune system as a whole is now quite well recognised, in particular for protection against respiratory virus they are important. It may be one of many factors (age, sex, co-morbidities etc) that contribute to how well you clear the infection and what disease you get.

I worked on a HCV trial in healthy volunteers in Oxford and we looked to see if the levels of vitamin B12 correlated with how well the individuals responded to the vaccine, we didn't see a correlation but this was a small trial. What we did notice is that many otherwise healthy individuals had lower Vit D12 levels than recommended - Leo

Hi Mods, we're done answering questions - thank you to everyone that commented! This AMA is now over (time: 17:27 BST)

Is there truth to the theory that bonemarrow "remembers" how to combat COVID and continues to produce antibodies even after recovering from and testing negative for COVID-19?

Also, what do you all think of the usage of medicines such as Ivermectin, hydroxychloroquine, and Lianhuaqingwen drugs to help combat or prevent COVID-19?

Thank you for doing this AMA, I highly appreciate all of you taking precious time out of your research to answer Reddit stranger's questions!

Yes, so one of the main jobs of the immune system is to remember past infections you've had so it can respond quicker and stronger the next time you encounter the same pathogen (virus/bacteria etc.). One form of this memory is antibodies (Abs), which B cells make that bind to the virus you previously had as soon as the virus enters your body, stopping the virus getting into cells and replicating. A special type of B cell called plasma cells stay in the bone marrow and release Abs into the blood. So after your body has naturally cleared the virus, and you now test negative, you continue to make Abs. Vaccines show the body a bit of the virus (often the spike protein for SARS-CoV-2) so that your body makes Abs without actually having to have the infection (its like a mock infection).

As for drugs, there have been mixed results with different drugs such as Hydrochloroquine. The main drug that has good evidence of improving outcomes after you've been infected and hospitalised are steroids. Ivermectin, hydroxychloroquine, and Lianhuaqingwen do not yet have good support for any effectiveness in lessening disease or the amount of time you are infected or hospitalised. These would all be therapeutics, given after infection mainly to lessen the symptoms and disease, not as preventatives given prophylactically before infection. - Leo

Thank you for answering so eloquently! I'd like to ask an additional question: have there been any studies or research into the effects of taking two or more vaccines (for example, AstraZeneca + Pfizer)?

Maybe the reply to mobilefern below answers this? :D - Leo

Do you know what is happening in our immune system to drive the symptoms of long COVID?

Hello,

Long COVID happens in 10% of COVID-19 infections and may be linked to the severity of disease. There are studies currently being done in this group of COVID-19 recovered patient so we will learn more about this soon. One of such studies already published suggest that there are certain alterations in function driven by initial COVID-19 infection in immune cells specifically the T cells that prevent the resolution of infection as we normally see in acute diseases

https://www.manchester.ac.uk/discover/news/altered-immune-signature-linked-to-long-covid/

https://www.sciencedirect.com/science/article/pii/S266663402100115X#fig4

I had COVID last year - how would I know if I'm still immune? And might I be better protected against new variants, say compared to someone who never had COVID?

There have been some big epidemiological studies now following people up to 6-8 months post-infection with SARS-CoV-2 which showed that the rate of new infections was much lower in those that had been previously infected compared to uninfected individuals. We can only keep monitoring people longer to see if this protection is lost over longer time periods and if infected people get infected again - we haven't had that long since SARS-CoV-2 has been circulating in humans yet to know.

This will be complicated by vaccines which will add another layer of protection. I was involved in a study looking at health care workers which showed after a single vaccine individuals who had been infected had stronger immunity than those that had not as it had boosted the natural immunity you had from the infection. This suggests maybe people who were previously infected only need one dose, but this is not policy yet as its hard to identify for sure those who have been infected and a second dose can only help in those that were previously infected.

What this study also showed is that the recognition of variants was stronger in people who had been infected then vaccinated than those who had just had one dose of vaccine. This is in the lab though, so we'll wait to see epidemiological data to support this.

Most vaccines just contain spike so you have an immune response just recognising this one part of the virus. Natural infection induces immune responses that recognise bits across the whole virus so may be better at cross-recognising variants. But this has not been shown conclusively yet. - Leo

Vaccines made polio basically disappear (though I know there are cases amongst people who did not get the vaccine). Is it likely that the COVID vaccines will make COVID a thing of the past?

Hey tonoocala,

Unfortunately it seems that total eradication is pretty unlikely. The vaccines are really successful at preventing serious disease and do greatly decrease the likelihood of becoming infected, but neither of these are 100%. This likely means that the vaccines will prevent the large majority of severe infections, but are less likely to completely eradicate the disease. The good news is that reinfections (or infection after vaccination) are generally much milder, so while the virus itself might still be around, actually developing disease will be much less likely. -Ryan

Dr Ryan Thwaites - says above that you study how the immune system contributes to severity but doesn't the immune system help us get better not worse from COVID?

Hey,

Good question (and one I'm spending my career asking)! When the immune system encounters a new virus it has to do two main things: 1) slow the virus down to try and limit the amount of damage the virus causes, and 2) learn how to kill the virus and eliminate it. In the majority of cases the immune system manages to do these two things without causing too much 'collateral damage' to the body. However, at least some of the time the methods the immune system uses to slow or kill the virus aren't completely specific, and the effects spill over into damaging uninfected cells or tissues.

This 'collateral damage' therefore means that the immune system is having some negative effects. In people with mild disease this damage might be very small, but in others it might be a big contributor to the overall severity of their disease. Some of my work studies the factors that determine whether the immune system will cause some of this collateral damage during an infection, and we know that things like your genetics and you age contribute to this. If we could understand these determinants we might be able to develop therapies that leave the beneficial roles of the immune system, while suppressing the harmful effects.

​

-Ryan

I received my first dose of Pfizer on April 7th & my 2nd shot is July 27 (for now). Our provincial government has finally opened up outdoor amenities. What are the risks if I play soccer outside with a friend who’s also been partly vaccinated? I have drills where we can distance, but do I still need to maintain a 6ft distance with him? What are some guidelines you can provide me? Thanks!

Hey! The first thing to note is that clearly at the moment no form of social contact is entirely risk-free. Even if you and your soccer team were fully vaccinated there would still be a (very small) chance that one of you could still be carrying the infection and pass it on. However, we can't avoid all contact, so the best thing is just to minimise the risks - for example you might agree that you won't go too close together when you challenge for the ball, or avoid tackling etc so that close physical contact is kept to a minimum. If you are playing outdoors then the risk should be very small , so the final thing to say is that you should avoid going somewhere else indoors after soccer finishes (restaurants, bars, houses etc) where transmitting the infection would be much more likely. Have a great game! - Ryan

What is encouraging is in large studies of people who have had one vaccine dose of Pfizer/BioNTech or AstraZeneca/Oxford vs. placebo one dose does seem to offer quite good protection from infection. The second dose is needed to boost immunity, so that some people who responded less well to the first dose are brought up to the same level as others and hopefully to increase the level or protection and maintain it over time. So its great that you've had one vaccine but vaccines are not cures, they are preventions, like Ryan said just reducing the risk of you becoming infected and in the cases where some vaccinated people have become infected they have much more mild disease. So risk of hospitalisation and death is much reduced. - Leo

My wife had been experiencing crippling headaches daily since she had covid about 3 months ago. Nothing seems to help it. Is this a common thing and do you know anything that could help?

hello, I am very sorry to hear that your wife is still poorly 3 months after covid-19 infection. It sounds like your wife may be experiencing what we know to be long COVID. This is seen in 10% of convalescent covid-19 that seem unable to - to put very mildly - 'shake' off the illness. There is a range of symptom people have reported to experience. Your Physician or GP will be in the best position to advice on this.

https://www.nhs.uk/conditions/coronavirus-covid-19/long-term-effects-of-coronavirus-long-covid/

Unfortunately, the science behind long covid is not yet clearly understood but our colleagues are working hard trying to to understand why some people develop this syndrome and how to prevent it or treat it.

​

Ane

In the past 3–4 months we learnt that the spike protein itself triggers vascular damage, crosses the BBB, and circulates in the plasma after mRNA vaccine injection. These seem to be quite different characteristics than other vaccines where the antigen is innocent. What does these discoveries mean for long-term vaccine safety?

(I am particularly thinking about a scenario where annual boosters are required for protection.)

Hi GentleStoic, This is not an area I know well I am afraid. The mRNA and ChAd (no replicative) technologies are meant to show the immune system the spike protein for a relatively short time, it is unlikely that spike protein will persist and be able to mediate this sort of side effect long term. I think if vascular injury by spike protein was common it would have been clear in the large trials so far, so it is also unlikely to be common.

All foreign proteins can cause immune responses and interact within the human host, we are learning new things about viral proteins from viruses we have studied for decades and all viruses that cause disease in humans need some special immune evasion mechanisms so its not unusual to see viral proteins used in other vaccines having off target effects. But prophylactic vaccines given to otherwise healthy individuals must be very safe and so these sorts of things are monitored very closely and it will be interesting to see if there is clear evidence of this effect of spike and what the mechanism could be. I think Ryan has some more information about Spike-Ace2 interaction related to this? - Leo

Is there any research into if covid-19 is oncogenic?

Coronaviruses, of which SARS-CoV-2 is one, have not been shown to integrate into the hosts genome, therefore are unlikely to be oncogenic in the same way HIV can be for instance. There is some very controversial data suggesting SARS-CoV-2 could intergrate but just from one group very recently and these highly technical experiments are hard to do and confirm that is definitely whats happening. I have seen no data of SARS-CoV-2 being oncogenic in general - Leo

Very sorry if we didn't get to your question! The British Society of Immunology have some great explanations of COVID-19 and vaccines here if you want more information: https://www.immunology.org/news/bsi-guide-vaccinations-for-covid-19

https://www.immunology.org/public-information

Will covid be like the flu where we need booster shot every year?

Hello, This is a possibility. It would depend on if we have new variants emerge that our immune system is not trained to detect and on how long our trained immune responses to COVID-19 lasts. If we can reduce the covid-19 pandemic to a situation where it can be managed like the flu with booster shots, this would count as a win too.

Ane

My friend in the US got Covid and recovered. She is early 20's. She still hasn't got her taste back completely and it's been a few months since testing negative. Is loss of taste a result of her own immune system going overboard or is it damage from the virus itself?

Hey, loss of taste (and/or smell) are quite common symptoms. Here in the UK the advice is that if these haven't returned after 6 months then different therapies and 'taste training' will be started; however, in the majority of people these return before this intervention is needed. The mechanism isn't fully understood, but we know that the infection can damage the nerves and accessory tissues that make taste and smell work. These nerves take a long time to recover and regrow, which can mean that the symptom persists a long time after the infection itself has been cleared. - Ryan

Hi, thank you for all the work you have done! I was wondering if we have enough information to model the within-host immune response against Covid-19 mathematically? And if so, what kind of information do you expect mathematical models to answer? Thank you very much!

Hi Yiping07,

Modelling has been used a lot to study the epidemiology of SARS-CoV-2 (how quickly it spreads, what impact can interventions have etc). To model any immune response would be the holy grail for us immunologists. We like to think that there are too many cell types and things interacting to make it really possible. Lots of differences between the host and viruses. But on a smaller scale we used modelling to look at how antibody responses are changing over time (https://www.medrxiv.org/content/10.1101/2020.11.04.20225920v2). Im sure people are incorporate measurements of different parts of the adaptive immune response (immune memory left after vaccination or infection) and outcome of infection to see which parts are playing a key role. Overall though, immunity is complex and many factors interact so its hard to tease out the relative contributions of different factors. I hope that explains a little of how modelling can be useful for immunologists - Leo

So realistically, is this virus just here to stay? What are the prospects of how the world might return to normal? Will it just be like the flu where we need to get a vaccine once a year or something? How much longer are we likely going to have all these travel restrictions and lockdowns? I’m in Southeast Asia for over a year now, and it seems like they have some incredibly draconian measures in some places that are absolutely wrecking the livelihoods of many the poorest people.

How much longer does this thing last realistically?

Hey,

The 'endgame' is really hard to speculate on so I'll give you my thoughts, but they are really just best guesses. I'll make a couple of assumptions - 1) the virus doesn't mutate in any way that meaningfully prevents vaccines from working in the future and 2) immunity is long-lived.

This virus will almost certainly be around for a long time, meaning it becomes 'endemic', likely as a seasonal virus in the colder/wetter months for much of the globe and predominantly infects people that aren't already immune. It may continue to infect people that have some immunity, but the evidence so far suggests that such infections will be mostly mild. So, as time goes and more of the global population develop immunity (by vaccination or infection) I expect we'll see the case numbers fall and the rates of hospitalisations and deaths fall even more sharply. This will mean that governments have to decide when the right time to open up the economy and return to normal is - this will likely have to be based on severe disease becoming rare, rather than total elimination of the virus. Each country is likely to take this decision differently, in addition to the fact that vaccination rates are very different between countries.

So, as much as we would like it to disappear overnight, that doesn't look likely and we will probably have a slow return to more normal life over the next year, with a lot of variation between countries. - Ryan

Covid seems to be mutating at a rapid rate. Are these mutations happening any faster in relation to other known viruses? How worried should we be about the speed of mutation? Will we continue to have to update vaccines and how often?

Hello, The coronavirus family to which SARS-CoV-2 - the virus that cause COVID-19 - belongs are relatively stable compared to say the HIV family. Coronaviruses mutate at a much slower rate. That said, we have seen variants of concern emerge so I would say that we have genuine reasons for concern. it is possible that as a result of these variants, we will have to continue to update the vaccine perhaps yearly like the flu depending on if our immune system is still able to efficiently neutralise these emerging variants and how long these immune responses last for.

Ane

I found this thread from a professor who works on the viral sequencing really interesting: https://twitter.com/BallouxFrancois/status/1395566513130774532 - Leo

Hi, it seems clear that Covid can be transmitted through droplets. Can it also be transmitted through the air and through surface contact ?

Hey,

The evidence certainly suggests that droplets are the major source of transmission. Droplets only travel a fairly short distance when people are speaking, but travel much further when coughing, singing, or shouting - so quiet voices are best! Airborne transmission has certainly been shown to be possible, but epidemiological studies suggest that this is much less of an issue than droplets, especially in well-ventilated rooms. Surface transmission is always such a concern with viruses, as some viruses hang around on surfaces for many hours. Fortunately SARS-CoV-2 seems to be quite short-lived on surfaces and this appears to be quite a rare route of transmission. - Ryan

Genetic material from SARS-CoV-2 virus can be detected on surfaces, for instance in COVID-19 wards and last different amounts of time on different surfaces but that does not necessarily equate to live virus that could cause an infection. Theres a lot we still don't know about routes of infection etc and modelling it in a lab does not always equate to real world situations. Its not our area of expertise as immunologists, sorry I can't be more specific than that! - Leo

Do the vaccines cover the double mutant from India?

This BBC article has a link to a study performed by public health England where they showed the vaccines work essentially as well against the variant first identified in India.

https://www.bbc.co.uk/news/uk-57214596

What we are starting to see is that the cross-recognition of the variants by the immune system can be lower when tested in the lab e.g. hypothetically only 70% of the antibodies that bind the Wuhan strain also bind the variant first identified in india, but when we look at epidemiological studies that is still enough antibody to protect as there are not more infections in vaccinated cohorts. Antibodies and T cells recognise many parts of the virus and viruses are constrained by what they can change and still be a functioning replicating virus so this multi-pronged attack is hard to evade completely. But the article above does show that you need both vaccine doses to give you a strong enough immunity to get good protection. - Leo

Is there a test available to the public to see if their T cells are reactive to SARS-CoV-2?

Last response before I have to go as this is my area of research! No publicly available test for T cells but people are working on it as it may be helpful in many situations to not only know the antibody response to SARS-CoV-2 but also the T cell response.

https://www.nature.com/articles/s41587-021-00920-9

T cells are immune cells that recognise infected cells and destroy the cell and virus together, and they also act to support B cells in producing antibodies among other things. Measuring them after vaccination and infection is likely to be important as they play such an important role in controlling viral infections. They also persist a very long time. 17 years after SARS-CoV-1 infection they can be detected in the blood of individuals who were infected. So maybe they are a good long term marker of who was infected, or they may be important for long term protection. Lots of unanswered questions for T cells as its more difficult to measure them than antibodies. - Leo

I am not aware of any such test at the moment. I know that there are plans to develop rapid tests for the clinics that would look at covid-19 reactive T cells. We would have to wait and see.

Ane

Do you foresee annual boosters being required for SARS-CoV-2 in the future? If so, for how long? And why? Thanks for doing this!

You are welcome. Its a pleasure to have this interaction with people regarding covid-19. Please see the answer to u/amypalgreen87 above.

Ane

Genetically speaking, how similar are the sars-cov-2 variants to the “wild” virus? In terms of epitopes, how would that affect the immune systems ability to recognize wild vs mutated variants? Is it your understanding that the spike protein is a single epitope or is it made up of more epitopes?

Hi, the dominant circulating strain depends on what part of the world you live in e.g the UK B.1.1.7 vs the Brazilian strain P1 and P2 vs the South African strain B.1.351. All currently circulating variants have been tested with serum from convalescent or vaccinated people and found to be effective at neutralising these variants to varying degree. One study found that the common D614G mutation rendered the virus more susceptible to neutralisation by antibodies while 2 other studies found that mutations in the receptor binding domain (RBD) of the spike protein made them less sensitive to neutralisation by antibodies. Certain strains carrying these RBD mutations are in circulation

Spike is a full protein that envelops the entire virus and forms the 'Corona' on the virus. as a protein, spike is made up of hundreds of amino acids which are organised into peptides. Each region of a group of amino acid is called a peptide and each peptide is potentially immunogenic. The immunogenic peptides contain an optimal epitope and there can be several of these in any one protein so I expect this would be the same with spike. There may be only a few immunodominant epitopes - these are epitopes that stimulate robust immune responses and can often account for the majority of the immune response to a protein

Ane

How much extra funding have you got since the start of the Pandemic?

Hi Needleworker, much research is funded by charities and by governments, in particular public money funded much of the basic researcher need to establish the Astrazeneca/Oxford vaccine! So researchers are acutely aware that they are responsible for using these funds to maximise the benefit to human health and grants are competitively awarded to try to ensure this. We don't get paid extra to do this research, to work weekends/evenings or to do public engagement etc. but its a privilege to do this job and so we have a responsibility to do it well. We also want to engage public as much as possible to find out their needs and show them what public money is used for.

COVID-19 research has been quite unique in that many people have changed to working on this global pandemic from their day job and so some have worked on it without getting any specific funding to work on COVID-19. UK-CIC is funded by UKRI and NIHR https://www.uk-cic.org/about-us/funders.

I have found it fascinating working in such a fast-paced field but researchers are also aware that other infections/cancers and health priorities haven't gone away so we are also keen to getting back to researching ways to improve human health related to these as well. - Leo

Should teens who have recovered from COVID be worried about long term effects?

As I mentioned above, if you have recovered and don't feel unwell then you should not worry specifically about long term effects emerging later. Most long-covid is a continuation of symptoms from the time of infection. Of course pay attention to your health and speak to your GP if you do feel unwell but there is no reason to worry specifically after recovering from SARS-CoV-2 - Leo

Is it fair to call Covid 19 an endothelial injury? And if so, are there any complement inhibitors being tested?

Hey,

The endothelium certainly seems to contribute to the pathology of COVID-19. There was some research looking into the possibility that SARS-CoV-2 could infect endothelial cells, but the current literature suggest this isn't the case. Even if these cells aren't infected, they seem to be activated during COVID-19 and secrete factors that contribute to the inflammatory response.

There is a lot of interest in testing complement inhibitors - you might be interested to look at this recent article that sums up the field much better than I can! (I hope it isn't behind a paywall for you) : https://immunology.sciencemag.org/content/6/59/eabj1014

- Ryan

What about the immune system of certain blood types that seem to be better suited to protect against Covid

Is there a statistical difference?

O we are just overloaded with news ?

There were early studies associating certain blood types with different outcomes. Blood groups can be genetically linked to many other factors meaning the blood group itself may not be the thing influencing it but another gene more common in individuals with that blood type. It is not a very strong risk factor. There is some discussion here:

https://knowablemagazine.org/article/health-disease/2020/covid19-and-immune-system-good-bad-and-ugly

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https://science.sciencemag.org/content/369/6508/eabc8511

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-Leo

Hello and thanks for doing this. Controversial question for sure but I have to know from people who should know...what are your thoughts on the USA’s response and constant flip flopping on rules for opening things, mask mandates, vaccination boosters, etc? It seems that we are finally getting tired of Fauci and his seemingly endless quest to stay relevant. He is making Americans start to question the “science” and that’s not good at all. And, what do you think about a person who was vaccinated (Pfizer) and still has arm pain and numbness after 4 months? I have not seen a doctor about it. And to be clear, I 100% believe Covid is here, deadly and not to be taken lightly. I was vaccinated as soon as I became eligible and my immediate family is the same. Unfortunately my wife and 12 year old son have had Covid. Still dealing with the effects with my wife and she got it on December 1st.

I am sorry to hear that your wife is still recovering and that you are still feeling the effects of the vaccine. I hope you both can see medical professionals about your symptoms and that you both recovery very soon!

It is very difficult to compare countries and even compare states within US on their approach. There are too many differences and we don't understand everything about this pandemic to interpret what worked or didn't completely yet. I think it will be an essential step in preparing for future pandemics but its hard to do it in real time now. Lockdowns and regulations are no ones first choice, it is a lot of tradeoffs between what can be tolerated and what is need /will be effective at minimising infections and disease. Working in public health is a very difficult job! Communication is key as you're all showing people want to be informed and it can be reassuring if the reasoning behind decisions is made public - Leo

Should people who have had COVID be worried?

Hi, Can you clarify what you mean? do you mean worried about re-infection?

Ane

Hi Yash-Pandya,
We are learning more and more about SARS-CoV-2 but theres still a lot of unusual things about this virus, for instance how can it take over the world can cause a pandemic like this when other viruses can't. I am for sure trying to reduce my risk of getting it by social distancing/wearing a mask etc but if you have had an infection and cleared it there is no reason to worry! The same as if you had had Flu and cleared it. Long-covid is something to think about and is an area of intense study but long term symptoms have been seen after other viruses before and hopefully we can get better at managing them.

If you mean worried about reinfection, I would say you should take the same steps to minimise risk of re-exposure as anyone else and also get vaccinated like everyone else to protect yourself and others!

- Leo

Also is there a difference between getting the virus as a adult (above 40) and a kid (under 16)?

We are very fortunate that it seems that children and younger adults natural immune response is very effective at clearing infection so few have severe disease. Age is a risk factor for more severe disease when you do get infected. Immunologists are still trying to work out how the immune system ages and why our susceptibility to infections changes over out lifetimes. - Leo