Previously we discussed the leaked news that the Oxford vaccine is producing both an antibody response and a T-cell response. 

This we noted was potentially very exciting news as some coronaviruses which cause the common cold in humans appear to be associated only with a weak antibody response which reduces rapidly. This might suggest that immunity would be short lived and reinfection just months after the first episode a real risk. If that was the case it seems we would be forced to deal with not just a second wave but many more, especially if vaccines didn’t work.

Video summary of this article

We also discuss in the previous post that reductions over time in antibody levels have been seen in some recovered COVID-19 patients. See https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1  

T cells are, however, known to be very important in tackling viral infections. And perhaps T cells might last for a very long time. This article outlines the data behind this and some new ideas regarding modelling which might suggest the much feared second wave will not emerge.

The 2nd Peak Uncertainty

18 July Update. Having refelected on this article overnight, I felt it was important for me to add a little bit of context at the front. This is setting forth one theory about whether or not countries which have already had a substantial wave off infections should be expecting a second wave. The truth is that there are arguements for and against this and we do not know yet what will actually happen. There is great uncertainty. I stand by the rest of the article which offers a case for why there may not be such a second wave. But I do not offer any degree of certainty that the eminent scientists expousing this view are going to turn out to be correct.

For balance, I thought I would share two further items this morning. Firstly an emiment scientific report that outlines the alternative option. Everyone up until now has assumed that with the relaxation of the lockdown and increased social mixing the disease would definitely spread a lot more. We are seeing that in some areas which did not have much spread first time round. But as we outline below that is not so far being seen in many areas that had a lot of cases early on including London (despite underground trains being crowded) and New York. Those two cities are definitely cases to watch. If there is not an increase in cases quite soon one might start to believe that the optimistic case outlined in the rest of this article is corrrect.

But it should be noted that many medical and scientific experts are concenred that this autumn a perfect storm of further relaxation of social distancing, the cold weather, the backlog of urgent medical cases that have not been dealt with, and the emergence of the flu season will combine to form a deadly and difficult period that might even eccclipse the first wave of earlier in 2020. This detailed UK report from a group of leading scientists outlines this perspective well and I should warn you makes frightening reading: https://acmedsci.ac.uk/file-download/51353957

However there is a glimmer of hope from Australia and other countries who are currently in their flu season. Even when the countries involved (including of course Australia) are not in full lock down the number of flu cases is vastly lower than ususual. It seems that basic respiratory hygeine and reduced international travel are combining to suppress the flu remarkably well. We can but hope that since our flu season is caused by spread from the South that we may also escape provided we do not completely abandon our protective measures. See https://www.who.int/docs/default-source/wpro—documents/emergency/surveillance/seasonal-influenza/influenza-20200701.pdf?sfvrsn=b3fcfc77_30

Let’s hope that the following measures which are reducing all respiratory infections continue and are taken up here.

• Hand washing
• Social distancing (2m where possilbe, 1m with protective measures)
• Use of masks
• Increased ventilation and avoiding groups indoors
• More testing for COVID19 and flu
• Not going to work when sick – strict isolation instead (including within the home)
• The vulnerable being extra careful
• Enhanced infection control mesures in care homes and hospitals
• Reduced international travel
• Track and trace systems
• Increased uptake of flu vaccinations (apparently seen in Australia)

Since blood cancer patients are vulnerable to severe side effects and bacterial infection on top of flu, if there is indeed to be a reduced flu season this year that would be good news for us.

Anyway this introduction helps set the scene for the fact that what follows remains a bit uncertain. The passage of time will show us which vision of the autumn for areas which have already had a big peak is correct – a huge second outbreak or the virus gradually reducing in its intensity perhaps with localised mini outbreaks. I am certainly hoping for the second and the rest of this article outlines the reasons why.

However, there is also some other new exciting evidence from one of the other two coronaviruses that have caused severe illness in humans and are believed to be very similar to COVID-19 – MERS and SARS. It turns out that a full seventeen years after SARS many patients still have a robust T cell response. Encouragingly these T cells are also strongly reactive to COVID-19. And remarkably some patients who had not been exposed to SARS had also previously developed T cells to other coronavirus which had activity towards COVID19. The assumption is that these have come from other coronaviruses. See https://www.nature.com/articles/s41586-020-2550-z

There is therefore now a growing suggestion that T cell responses to other types of coronavirus, even including the cold causing species may be crucial to protecting some people from COVID19.  This could help explain why those areas which had severe outbreaks of SARS and MERS seem to have been relatively spared from COVID19. Of course, this is complicated by the fact that the same areas have been much more willing to use face masks given that prior experience.

This idea of cross-immunity from other coronaviruses including some of the cold causing species is core to a new publication just released from Oxford University which we will now discuss. See https://www.medrxiv.org/content/10.1101/2020.07.15.20154294v1

The much-maligned concept of herd immunity is actually completely crucial for us to find a way out of the global crisis we are in. Until we reach the threshold of protection from infection or vaccination another deadly wave of COVID19 could break out and we will all remain vulnerable. Even low levels of COVID19 in the population are very worrying for those of us with blood cancer or other reasons to be extremely vulnerable to severe side effects and even death from COVID19.

The new Oxford paper questions the received wisdom that the herd immunity threshold for COVID19 is well over 50% of a population being unable to transmit the virus. Those original calculations were based on the idea that nobody in the world population had any immunity before January 2020 and that everyone had the same likelihood of being susceptible to the disease. It is becoming clear however that the risk of infection is not uniformly distributed across the population.

Oxford scientists here propose that some people may be able to fight off COVID19 by means of a sufficiently strong innate immunity.  This is caused by neutrophils and other parts of the immune system which are not specific to a particular disease.  If your body stops the virus in this way you may not get an opportunity to develop antibodies. As an individual perhaps you might remain vulnerable to a higher dose of the virus at a later stage. But presumably you also did not get sick and did not pass on the virus to others.

They also suggest that perhaps some of the seasonal cold-causing coronavirus may have induced immunity due to the T cells. They review some of the other evidence emerging that T cells produced in response to circulating cold causing coronaviruses may produce some immunity to COVID19 citing three other papers: https://www.cell.com/cell/pdf/S0092-8674(20)30610-3.pdf  , https://immunology.sciencemag.org/content/5/48/eabd2071 and  https://immunology.sciencemag.org/content/5/48/eabd2071

Those individuals who already have T cells active against COVID19 would be less able to develop or pass on the disease. Unfortunately for blood cancer patients many of us even before treatment, and certainly after, have poor T cell-based immunity and this might contribute to the greater susceptibility seen towards severe complications.

The concept is that even at the beginning of the outbreak the population would therefore vary in their immunity to the disease.  This might explain why some really old people seem to get very mild or no disease, whilst some young people have sadly succumbed.  It would also explain the pattern where there is a rapid burst of infection in a population that is first exposed to the disease.  Those who are catching the disease in that first wave are mostly those who are particularly at risk from it.  As the sickness spreads, however, it finds that the remaining parts of the population are less and less likely to be as severely vulnerable to it.  In this way you would expect the rate of spread to slow down long before the population reached the theoretical threshold of herd immunity previously suggested. 

This new theory does seem to follow the pattern of spread seen in many countries, especially when lock downs have been used.  Over time the degree of mixing between the susceptible and non-susceptible groups would be crucial to the rate of transmission of the disease.

According  to the new Oxford model, herd immunity will only require 25% of the population to have been infected if half the population is resistant and the mixing between the resistant and non-resistant parts of the population is fully random.  If on the other hand those who are resistant are more likely to mix with other people who are resistant then this figure would drop further, and Ro would need to be above 2 to produce a new epidemic spike or second wave.

Thus the Oxford study offers the tantalising prospect that perhaps we already have enough immunity within the population of the UK and some other countries to prevent the second wave we are all worrying about. Low grade spread of the disease might continue but even that would presumably eventually die out.

Gabriella Gomes a UK mathematician has come to a similar theory. She defines two scenarios. One where the population has the same level of risk of catching the disease (homogeneous) and one where there is variation in immunity even at the start of the epidemic (heterogeneous)

“There doesn’t need to be a lot of variation in a population for epidemics to slow down quite drastically . . . Even if the two populations start out with the same average susceptibility to infection, you don’t get the same epidemics.

The outbreaks look similar at the beginning. But in the heterogeneous population, individuals are not infected at random. The highly susceptible people are more likely to get infected first. As a result, the average susceptibility gets lower and lower over time.”

Gabriella Gomes quoted in https://www.theatlantic.com/health/archive/2020/07/herd-immunity-coronavirus/614035/

The Atlantic goes on to suggest that this model would predict a gradual slowing of the epidemic after an initial spike even if only 20% of the population is immune to the virus. This would support the observations so far seen where cities like London and New York which were severely affected by initial spikes have been able to slowly relax their lockdowns without so far  seeing a second peak in cases.

Of course, there is huge uncertainty around all these models. But many of us have been surprised and alarmed by images of crowded underground trains, packed parks, huge demonstrations, mass day trips to beaches, and more latterly pubs and restaurants opening up. Despite all this neither London nor New York are seeing a second peak developing just yet.  We will all watch this space with much interest in the coming weeks.

This all doesn’t provide any comfort for towns and cities yet to really have their first peak. And thus the new models could also support the pattern being seen in other parts of the USA which one could argue had perhaps locked down too early, before they even had a peak, or did not lock down at all, and as a result are only seeing their first peaks now.

One factor neither articles considers is what is the effect of protecting a huge number of people who are presumed to be highly vulnerable to severe side effects and even death from this disease – the 2 million “shielders” in the UK.   

If we and other countries have been successful in identifying a group of people who are at particular risk, and have protected them during the first wave, what happens when that group is released into a society that now has low levels of background infection?  Is there a risk that the spread accelerates rapidly through the vulnerable population as it has done sometimes when it finds its way into an environment like a nursing home?

Or will shielding turn out to have been an absolutely brilliant idea since we protected ourselves during the initial peak, and at low levels of background infection currently seen in the general population even as we emerge from our cocoon will we remain at very low risk of catching this dreadful disease?

As many of us consider our own personal risk assessments and how much we are willing to relax our social isolation measures, this modelling makes fascinating reading. We will want to keep a close eye on local infection rates to identify any signs of a new wave of infections. Facts mean much more than theories at times of huge uncertainty.

In any case while there is still evidence for community spread many of us are going to want to maintain at least some of our risk reduction measures. The fact that a vaccine may not be far away also has an influence. Certainly, for myself I do not want to have spent all these months in strict isolation and then catch COVID19 only a short while before a vaccination program might bring accelerate the natural end of this epidemic.

Perhaps the most encouraging feature of all that has been discussed in this article and yesterday’s news about the vaccine is that together this holds out the hope that just maybe immunity to COVID19 whether caused by an infection or vaccination might be much longer-lived than we have feared might be the case. If so, then this might reduce or perhaps even eliminate the risk of this turning into a seasonal disease like flu where we get regular outbreaks every year. Let’s hope this is turns out to be the case, which would mean that we might therefore all face a brighter future where COVID-19 soon becomes a grim but distant memory.

Read More

The Atlantic https://www.theatlantic.com/health/archive/2020/07/herd-immunity-coronavirus/614035/

Science Mag https://blogs.sciencemag.org/pipeline/archives/2020/07/15/new-data-on-t-cells-and-the-coronavirus