(98) Coronavirus update: oh, how beautiful is denmark

In the new episode of the NDR Info podcast Coronavirus Update, virologist Sandra Ciesek talks about new data on vaccination of pregnant women and children under twelve, vaccine breakthroughs and the My variant.

5.7 billion doses of vaccine have been given against coronavirus worldwide, yet vaccination coverage is stalling in many countries. But wherever research looks, vaccination seems to be the only way out of the pandemic. In an interview with NDR Info science editor Korinna Henning, virologist Sandra Ciesek looks to Denmark in episode 98, because our neighbors are several steps ahead of us when it comes to vaccination. Also, the NDR Info podcast coronavirus update talks about vaccinating pregnant women and children under twelve, as well as the risks of the delta variant, and much more.

An overview of the central themes of the episode – click to jump directly to the text passage

Korinna Hennig: We have to start off by doing a little wrap-up of our last podcast episode, which was not with you at all, but with Christian Drosten. This was the week before last. There was some excitement on social media. We talked about how dealing with the virus can be when we are in an endemic situation. So when the greatest pressure on the health care system and society is over.

Christian Drosten has described that in the long term it can amount to double vaccinated people becoming infected with the virus and then probably and hopefully having a harmless course of the disease. But there were abbreviations in various reports on the podcast. That sounded to some a bit like you should now tear off your masks as a vaccinated person and seek an encounter with the virus. Let’s get this straight together again: We are nowhere near that point, and it’s not about measles parties.

Sandra Ciesek: No, it was certainly not meant to infect on purpose. So according to the motto: Oh, next week I have nothing planned and have time to get infected. Then I go through the infection between Tuesday and Friday and am fit again for the weekend. This was certainly not meant. He simply presented a not improbable, if not the most realistic scenario and tried to explain how it will look like in the endemic situation. What can be noted, I think, is that the virus remains. This is clear for many.

But some people still have the hope that they will never encounter this virus, that they will never become infected. I think you have to be very clear there that of course the virus will eventually become endemic as well. Just like the other endemic coronaviruses, or hundreds of other respiratory pathogens. So, that we can have repeated contact with this virus and with these viruses.

Why the vaccination rate must be increased now. Also: Pregnancy vaccination, delta risks and the My-variant.

00:01:35 Transition to endemicity
00:04:17 Duration of immunity and breakthrough infections with Delta
00:08:13 Age structure in German intensive care units
00:11:45 Comparing vaccination risks with viral infection consequences
00:17:53 Socioeconomic dimension in testing and disease progression
00:26:13 Obesity and other risk factors for breakthrough infections
00:39:33 Relationship between vaccination coverage and childhood illnesses
00:47:52 School quarantine and compulsory testing
00:52:53 Myocarditis risk with adolescent vaccination
01:00:54 Time perspective child vaccination U12
01:05:29 New data on vaccination of pregnant women
01:18:02 The example of Denmark
01:24:48 Viral evolution and the My variant

Not a day goes by without new news on the Sars-CoV-2 coronavirus. We have long since become accustomed to measures such as mouth protection, distance and hygiene rules. And still no end to the pandemic in sight. In our bi-weekly podcast, we aim to provide reliable updates on new research findings. What about a vaccine? How does the testing strategy evolve? Is there hope for a drug? NDR science editor Korinna Hennig and Beke Schulmann from the science editorial team take it in turns to talk to Christian Drosten, head of virology at the Charite hospital in Berlin, and Sandra Ciesek, head of the Institute of Medical Virology at the University Hospital in Frankfurt. This is not about scaremongering – but quite the opposite: the podcast "Coronavirus Update wants to inform, classify and provide background information.

If anyone has a question for the podcast interviews with Christian Drosten and Sandra Ciesek, please feel free to email it to: [email protected]

#coronavirus #covid19 #covid_19 #coronavirusupdate

Transition to Endemic

After all, we do not live in complete isolation or completely sterile. Then regular contact leads to immune responses. Immune system remembers and creates new antibodies. That’s actually generally the case with many infections. What is also important to mention: Someone who is fully vaccinated has minimized the risk for himself to get a severe course or even to die from the infection. And vaccination is therefore a very important step towards endemicity. What else is important Not the virus has weakened so far – on the contrary, we see more contagious variants. In part, it is even suspected that there is a severe course. The impact of the virus is reduced by vaccination.

Hennig: About the course of breakthrough infections: They are often asymptomatic, but in some individual cases, despite double vaccination, they are symptomatic. There are also sometimes severe courses. We can learn a lot from the U.S., where the CDC, the U.S. Centers for Disease Control, documents this very well. Are there any new findings for you from the data that we now currently have??

Ciesek: Yes. There is also published data, but it mostly pre-dates Delta. So to get away from the U.S. again, there’s a preprint from Qatar where they did a meta-analysis. Meta-analyses are, after all, statistical procedures that summarize the results of several studies. So we always see here in the everyday life of the podcast that there are studies that say "giddyup", the other study says "hott". Then there are five studies that say "giddyup", and one says "hott. These meta-analyses are supposed to break it down a bit like that.

And they’ve looked at over 9.000 studies and then finally included 54 that were qualitatively good enough. These come from different countries, Canada, USA, South America, Europe and also China. They looked at: How long do people actually have antibodies?? How long do they have T and B cells during infection and after recovery? It was seen that six to eight months after the infection, more than 90 percent still had antibodies, i.e. IgG antibodies.

Duration of immunity and breakthrough infections with delta

Unfortunately, the data on T-cells, i.e. CD4 and memory B-cells, are less good. There is actually only one study. But even there the values are very high, with almost 92 percent or memory-B 82 percent. What’s important in this data is also the number of reinfections, which is that it was only 0.2 percent reinfections. But as I said, this is where the data was analyzed, and the studies that predate Delta. But if you look in the USA and look at the delta data, they are always published by the CDC.

They looked at 10. September a report in the Mobility and Mortality Weekly Report brought out. That is quite interesting. Of course, it is well known, as we see here, that the incidence of infections and hospitalizations and deaths is higher in unvaccinated persons than in vaccinated persons.

Situation before and after Delta

But what exactly is the situation before Delta and after Delta?? So before Delta became dominant and after? They also looked at this. You can see here that the ratio of vaccinated versus unvaccinated for hospitalizations and deaths has changed relatively little. So it’s still the case that unvaccinated people in particular have to be hospitalized or die. Which suggests that the vaccines also have a sustained and high efficacy against severe courses of Covid-19.

But what they also saw is that the effectiveness of the vaccine in protecting against infection was reduced. This means that it was possible to become infected and that this unfortunately occurred more frequently than Delta became dominant, but that the severe courses, i.e. that someone had to go to hospital or died, could fortunately still be effectively prevented in most cases by vaccination.

The coronavirus © CDC on Unsplash Photo: CDC on Unsplash

(98) Oh, how beautiful is Denmark

Topics u.a.: the myocarditis risk in adolescents vaccination, time perspective child vaccination U12 and the relaxations in Denmark. Download (300 KB)

Therefore, the message of the CDC to the citizens is the same as the message of the RKI, that you should simply get vaccinated, even if you can then be infected with Delta, even if you can then be contagious. In this way, however, they tried to reduce the risk of having a severe course for themselves.

Age structure in German intensive care units

Hennig: In terms of incidences, if we now look at Germany, you can see in the DIVI registry who are the people who end up in intensive care units. Currently, a quarter of covid 19 cases in the ICU in Germany are between 50 and 59 years old. This turned around in the middle of August. Until then, i.e. also in the summer, the over 60-year-olds still had the largest proportion.

And this was also the case during the third wave with the alpha variant in the spring, followed by the over 70s. So the virus is now slowly moving further and further down the age scale. This was predicted a little bit. Nevertheless, once again: What is the explanation? Is it mainly the vaccination status and because delta might make you a little bit sicker, so it’s affecting younger people as well? Or are there other factors at play, behavior and network functions of those infected?

Ciesek: Yes, probably all a little bit. But these are quite impressive figures, if you look at this figure from the DIVI register again, who is really in intensive care at the moment?? At the moment, the proportion of 30 to 39 year olds, who probably consider their risk to be quite low and who are often not vaccinated, is higher than the proportion of 80 year olds, 80 plus, who are probably vaccinated for the most part. Of course, you have to think about this carefully if you are in the situation and are faced with the question: Do I get vaccinated, do I have any risk at all at the age of 35??

And what I also find impressive is that really half of the patients or more than half are under 60. So it is not a disease of pensioners or residents of old people’s homes, but it is a disease that now also affects people in the prime of life, I would say in middle age. You have actually just mentioned the reasons. Of course, many more of the 80-plus have been vaccinated than of the 30-year-olds.

Role of the Number of contacts

But it also plays a role in how many contacts I have. I would say that probably a 30-year-old has more contacts per day than an 85-year-old, at least on average. Of course, this gives the virus more contacts and makes it easier for it to spread. Delta is even more infectious. Behavior is also important, of course. That if I’m not worried about a severe course, maybe I’m not avoiding infection at all and being as careful as someone who is scared. Therefore, it is a combination of many things. If you look at individual patients who are now seriously ill, you get the feeling that very many have deliberately decided against vaccinations.

But there is also another part of the patients. So sometimes you wonder where they’ve been for the last year and a half. A colleague told me the other day that he had a seriously ill person and the relatives didn’t even know what a quarantine was. So, they’ve really been passed by the whole pandemic so far, the pandemic hasn’t, they’ll have noticed that, but this knowledge about it has really passed them by. I think there’s a lot of work to be done to kind of reach those two groups.

Comparison of vaccination risks with consequences of viral infection

Hennig: Then there’s the group in between, which maybe plays a lot with the younger ones, with the 30- to 39-year-olds. They say: In the risk-benefit analysis of such a vaccination, I don’t see any great danger for me. At the beginning of the pandemic, we only talked about the risk posed by the virus to the very old and the previously ill. Now many are talking more about the risk from vaccination. There is a study from the "New England Journal of Medicine". Israeli researchers, in collaboration with Harvard colleagues, have cleaned up and analyzed health insurance data from Israel.

They actually contrast that quite impressively with the risks of infection versus possible side effects of vaccination. In this case at Biontech/Pfizer. What does the data tell you there? What are the main risks? Myocarditis comes to mind, this has been discussed a lot in connection with infections, but especially with vaccination.

Ciesek: Exactly. This New England Journal-Anyone can look at the study. It came out at the end of August. It’s really an insane amount of data from over two million people. They didn’t just look at the vaccinated data, they compared it to a collective that went through SARS-CoV-2 infection to get a feel: What is actually more common? That is the question especially with myocarditis. And if you compare that, it’s more than three times more likely to occur after infection than after vaccination. This is very important data.

Hennig: However, for the sake of completeness, it must be said that lymphadenopathy, i.e. swelling of the lymph nodes, has been observed in rare cases in connection with vaccination. And in 16 per 100.000 vaccinations was a herpes zoster infection, that is, shingles. This was already a topic here in the podcast. But these are rather rare abnormalities in comparison. And much less dangerous than the side effects of a viral infection, or?

Ciesek: Exactly that. Other adverse events of a serious nature also occur after infection that are not seen after vaccination, such as cardiac arrhythmias, thrombosis, pulmonary embolism, myocardial infarction, or even bleeding in the brain and a decrease in platelets. All this can occur after the infection, but was not seen in connection with the vaccination with Biontech/Pfizer.

It’s not that rare. So, in any case, when you look at the study, you come to the conclusion that the vaccine is not associated with an increased risk of most adverse events. And that the vaccine is associated with an increased risk of myocarditis, that has been discussed several times and that this risk is lower than after an infection.

Hennig: As far as vaccines are concerned, I remember that at the beginning of vaccine development there was sometimes a concern that there might be a side effect known from other vaccines, namely "antibody-dependent enhancement", So infection-enhancing antibodies. We’ve already discussed that in the podcast. So that, to put it simply, a bad inflammatory reaction is actually triggered by the vaccination in the first place. This was an open question, but it does not seem to have occurred. What is the explanation?

Ciesek: It’s like, if you go to medical school and then you have the virology clerkship, you learn this antibody-dependent enhancement classically in dengue virus infection. This is the classic way to explain it. And you have a dengue virus infection. Antibodies are then formed. There are different serotypes of the dengue virus.

If you get a second infection, for example because you live in an area where these mosquitoes live – it is transmitted by mosquitoes – with a different serotype, then the old antibodies bind this virus with the other serotype, but cannot neutralize it, i.e. make it harmless. This binding, however, leads to the fact that the antibodies are then recognized by immune cells, i.e. by macrophages, and the virus is then carried to them and infects them. That, in turn, leads to a stronger replication of the virus, so the virus can spread even more efficiently, can disrupt the immune system, and the virus can just replicate better.

Graphic representation of a coronavirus © COLOURBOX Photo: Volodymyr Horbovyy

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Dengue vaccines

It’s so this classic mechanism. That’s why you have to be careful with dengue vaccines and look carefully at how you design them. Now we come to SARS of 2003. It has been shown in animal models, in mice, under very specific conditions in the laboratory, that antibodies against nucleocapsid, if induced by vaccination, can make subsequent infections worse. That’s why with SARS-CoV-2 they didn’t decide very early on to vaccinate against nucleocapsid, but all vaccines are based on spike, so they were designed against spike.

Hennig: So different proteins of the virus.

Ciesek: Exactly, these are both proteins. This effect in the animal model mainly concerns nucleocapsids. That’s why, of course, they looked at the old data during development and said: No, we won’t use that, we’ll use Spike instead. And so minimizes the risk. But you also have to say that, for example, unlike dengue, the SARS coronavirus actually can’t infect macrophages very efficiently – if at all.

So that this mechanism is broken there as well. If someone says, I still don’t believe it, then you have to say that the facts simply speak against it. If we look at the intensive care unit, it is mainly the unvaccinated who are seriously ill, and not the people who have been vaccinated. If there was a really significant antibody-dependent-enhancement effect, the ratio would certainly be reversed, and it just isn’t. So I think the reality has shown that that’s just not the case.

Socioeconomic dimension in testing and disease progression

Hennig: So in summary: There is a growing body of data on the safety and efficacy of vaccination. Let’s go back to the group of unvaccinated people that every piece of information has passed by so far. There are relatively clear indications from the research that socioeconomic factors play a major role. Now we have a new study from Switzerland that at least looks at the number of tests for the virus and the course of the disease for different groupings. There again, the data speak pretty clearly. How is all this related to each other??

Ciesek: Yes, that’s quite interesting, this data from Switzerland. And what they wanted to do was to investigate whether inequalities in patient care become traceable. They looked at reporting data on testing, but also on hospitalization and ICU admission, death by covid-19. They then correlated that with a score that describes neighborhoods based on factors such as rent, education, occupation and population density. So they’ve looked at all these factors as well.

What you see is that the higher that value, so the more privileged people were, the more testing was done in those areas. And when you compare that, there was less testing for Covid in socially deprived areas. But also the positive rate was lower and also the rate of hospitalizations, intensive care stays and the deaths were lower in these privileged areas in comparison.

Inverse Care Law

And in the opposite case, where the socioeconomically disadvantaged live, there was less testing and they were still more affected. This is an inequality called the Inverse Care Law. That is, those who actually need the medical measures like testing the most have received them the least. The data seem to show that again impressively.

I don’t think that’s in there now that it’s similar for vaccinations, that probably in the privileged areas the vaccination rate tends to be higher than in the more deprived areas. I think that is also a very important message to politicians in this paper: that they have the task of ensuring that we can also reach these groups and eliminate this inequality a little bit.

Hennig: Especially, of course, with vaccination, because it’s free of charge. There’s also always a discussion about whether people are actually being reached with the vaccination offer. Jens Spahn, the Minister of Health, once said that by now everyone should actually have been reached by an offer of vaccination. Now you just gave the example of the family that had never heard of quarantine. How great is your hope that some strata, some groups will even be reached by this enlightenment? And especially how?

Ciesek: That is a very good question. I am not an expert at all. There are certainly experts who can do this much better or know what can be done. I don’t think our podcast listeners, because that is of course also a selection. Who listens to such a podcast consciously, wants to inform himself. But you simply must not assume that this is the normal state of affairs. I think you should try to reach these people through employers.

Everyone who listens to the podcast about direct contact, i.e. if you have someone in your environment, and if it’s the cleaning lady at work, that you simply get into conversation with her, also take care of your fellow human beings and address them and maybe answer questions or name someone you can contact.

Language barriers

For me, the linguistic aspect is still a big problem. Even though we live in Germany, it’s not enough just to put an ad in the German FAZ about a page. With this you will not reach those you want to reach. I think it’s important for those who are simply unsure: You need clear communication. So that you don’t say: Let’s all get vaccinated, it’s all quite harmless. But that one really quite clearly also lists the limits of vaccination and the risks. And nevertheless also the advantages reflects, which has a vaccination.

I think if people just feel persuaded or not educated openly and honestly, it tends to have the opposite effect. For example, I find the comparison as in the "New England Journal" very important very important that when you argue that it makes myocarditis, you can say: Yes, but if you have an infection, and you will eventually get it, your risk is three to four times higher. I think that is really important. And of course, I think you simply have to get to these people again somehow, for example by addressing them directly.

Information about vaccination by mail

So that they get a letter home for a conversation with a doctor, to simply talk about vaccination again. You don’t have to do it for everyone, but at least for those over 50 who have a really high risk. I also checked again that now in Germany, 17 percent of people over 60 are still not vaccinated. This is really a group, we really have to make an effort to reach out to them. I think that’s where primary care physicians or face-to-face conversations are also important, because there’s always a different quality to that when you look someone in the eye in a conversation.

Maybe a personal approach will simply bring a little more. One can certainly also say that if one thinks for oneself that one has no risk, then perhaps one does the vaccination for the others. So that one then says, if I have now decided for myself in this way – which I cannot understand, but can be the case – then one can still say: Good, then vaccinate yourself for the others, vaccinate yourself for your grandmother, for your neighbor who is a kidney transplant, vaccinate yourself for your little cousin who cannot be vaccinated.

solidarity on the subject of vaccination

I think it also has a bit to do with group thinking and solidarity, to decide in favor of vaccination, because it is simply not a decision to be made alone. Because it’s an infectious disease that’s contagious, it’s a different decision than if I decide to drink alcohol. I think it’s really important that we, as a society, stay in touch and that we really look around to see if we can approach people and say, "Come on, I’ll help you. I explain this again. I think the podcast listeners are also very well equipped for that, so to go into conversations, and they also know many arguments that are then easy to refute.

Hennig: By vaccinating, I am of course also protecting others who may have been vaccinated twice, but who, because of certain previous illnesses, have a greater risk that the vaccination will not work perfectly for them and that, if they are then infected again, they will become ill again.

Ciesek: Yes, that is true. You have to keep in mind that we’re seeing more frequently now with Delta that even after two vaccinations, there can be an infection and people can re-infect others as well. That’s what I mean by open communication and honesty.

Continue to protect high-risk contacts

So you can’t say: Vaccinate yourself, then you can go back to your grandma in the old people’s home. I would still be careful. So I have now decided for myself that I am vaccinated. But if I have a risk contact, if I go to someone who I know has a problem and perhaps doesn’t have good vaccination protection, then I still do another test beforehand, for example, or I definitely don’t take off the mask.

Hennig: But vaccination and test are still better, even for others, than just test.

Ciesek: Definitely, clearly. I don’t want to say that now. We will probably now be quoted again in abbreviated form as having said: Testing is enough. No, of course not. You also have to get vaccinated, simply because then, of course, you are demonstrably less infectious for a long time and usually also excrete fewer viruses. But the risk is not zero.

Hennig: In the case of these diseases despite vaccination with the delta variant, the same risk factors actually play a role as they do for the coronavirus in general? So we know the cardiovascular diseases, diabetes, being immunosuppressed, but also overweight, which is perhaps always a bit underestimated, because it is a disease of civilization and you may not really feel sick as a slightly overweight person.

Ciesek: Yes, they are similar. If one looks again at the overweight, then the question is: Where does this come from?? And is that a causal relationship? So is that really the case, that there is a plausible biological mechanism that leads to the fact that you have a risk factor through being overweight?

Obesity and others Risk factors for breakthrough infections

There’s a nice summary from the Mayo Clinic in the journal from them. And you can answer that briefly: Yes, there are medical reasons. For one thing, obese people have a significantly higher pressure than normal weight people on the lung tissue, so because of the weight. Therefore obese people simply have to do more breathing work. The overweight puts a strain on the cardiovascular system.

And then, when they get infected, yes, the lungs are infected with the virus and so that’s also a burden on the lungs from the inside and from the outside. Then we know that obesity usually does not occur alone, but is a major risk factor for cardiovascular diseases, for high blood pressure, for an increase in cholesterol, for type 2 diabetes and has overall negative effects on the cardiovascular system. And the body’s immune defense is also somewhat different with obesity.

Higher risk of thrombosis with obesity

There is chronic inflammation, i.e. endocrinologically speaking. And, perhaps most importantly, obese people are more prone to thromboembolic events, i.e. thrombosis. This is also a central pathogenesis in Covid-19, which plays a role there. What certainly also plays a role are the socioeconomic reasons, which we have already discussed.

Because, if you look, obesity is probably more common in people with low incomes. The knowledge about healthy nutrition is rarer there and often also the money for the healthy nutrition is missing. Or people are eating the wrong foods. And that certainly plays a role. And mostly several factors come together.

Hennig: The link to the Mayo Clinic we put here of course also with us in the Shownotes. To summarize: There are very different levels at which this plays out, hormonally, purely mechanically, in terms of secondary diseases and so on. If we broaden our view a bit from this problem of overweight, then there are also more and more findings on the question of who is affected by such symptomatic and possibly also severe breakthrough infections.

So in terms of other pre-existing conditions. Or completely different factors. There is an evaluation from Yale, which has now been published. I have calculated a figure here – correct me if it is wrong – they examined 969 patients, and 5.5 percent of the patients were fully vaccinated and only about one percent were fully vaccinated and had a severe course of the disease. Nevertheless, who was that?

Ciesek: I’m not that good at mental arithmetic. Unfortunately I do not have a calculator. But exactly, there were just under a thousand cases and 54 were hospitalized after vaccination. And that from the period until July, that speaks rather for the fact that it was not yet necessarily Delta. It was interesting that 46 percent were asymptomatic. That is, these were random diagnoses. Often screenings for the virus are done at hospital admissions and almost half of them had no symptoms at all and knew nothing about it.

Then seven percent were mildly symptomatic, a bit of cold disease, but still 20 were moderately ill and 26 had a very severe course. But then they looked at it again: Who has a severe course, these 26 percent?? And here it is interesting to know that the median age of severe course after vaccination was 80.5 years. So these were the older ones that are now also being discussed or where it has already been started that they are vaccinated a third time. And after all, three of them have died.

Diseases in old age as a risk for breakthrough infections

Age did not come alone. Just like obesity, this often does not occur alone. There were also comorbidities, i.e. other diseases such as obesity, cardiovascular diseases are also common at that age, and some had cancer or diabetes or lung diseases. Of course, this all plays a role, so if someone has several risk factors, then is 80 years old. These data show: What does the patient look like at the moment who has a breakthrough infection despite vaccination?? And as said, the median age 80.5 years.

Hennig: Now add to that the delta variant. Here, in this Yale study, Delta was probably not really in yet. Or if, then only a little bit. That has not been broken down there. If now Delta possibly increases such breakthrough infections, what could be the reason for that? Do we know a little bit more? Is it mainly the variant that makes you sicker? Or is it also more still the waning immunity?

Ciesek: That is quite an interesting question. And the waning immunity would speak for it, and there it is important for our management of the third vaccination to decide or to commit to that. I have looked at this.

Influence of Delta on breakthrough infections

And I personally actually believe that the increase in breakthrough infections is mainly, most of it, due to delta and not necessarily due to declining immunity. And why do I believe that? As I said, antibody levels always decrease after vaccination, if you observe that. Now that’s not specific to this vaccination, but in general. They drop off slowly and steadily and are not gone all at once.

Sure, there’s probably a threshold then as well. But if you look at all the literature and preprints on these breakthrough infections with Delta, you have to go back to how we vaccinated, so last December or January. We started in January, vaccinating mainly in the old people’s homes and people over 80 years old. The second thing we’ve done is vaccinate the medical staff or the nursing staff in the hospitals that have been dealing with covid patients and treating them.

And now if waning immunity was the reason that breakthrough infections were occurring, then we would expect that those groups would have the breakthrough infections first and the others would follow at a certain interval. So that you then see the 60-year-olds, then the 40-year-olds, then the very young ones. And you just don’t see that.

USA: Rather younger adults with breakthrough infections

So if you look in the U.S. and you look at the data there, it’s more the other way around, which is that younger adults or those with a lot of contacts had these breakthrough infections and not the older 80-plus year olds. To me, that speaks a little bit for the fact that this is really triggered by delta rather than by reduced immunity, because, as I said, the sequence would then be different.

And there is also a lot of data from the U.S., where they really compared it in the different states, and also there they don’t see a connection to the time of vaccination and that then someone gets a breakthrough infection earlier compared to other states, where they vaccinated later, for example.

Hennig: But that means that an adapted vaccine would actually be nice.

Ciesek: Yes, definitely. What you also see, for example, is that breakthrough infections occur in regions where delta occurred first. As I said, the data from the U.S. And not in areas that became dominant later for Delta. And here it is also the case that the breakthrough infections tended to occur where Delta became dominant, rather than where vaccination was carried out particularly early. As I said, you can sort of glean that a little bit from looking at the preprints, looking at all of the literature. A low vaccination rate and a high delta dominance just leads to you having a lot of infections overall.

Booster vaccination against Corona infection

What does that actually mean for booster vaccinations, if you see now that it’s more because of delta than because of waning immunity? We are not now completely flooded in the hospital with people who have a breakthrough infection. But at the moment it’s a pandemic of the unvaccinated in the hospital. That has to be said very clearly. That speaks in favor of refreshing those who are known to have no immune response or no efficient, no good immune response – such as dialysis patients, patients over 80 or even over 70 or 60.

I think there is already data for that as well. But with the still insufficient vaccine production worldwide and the numbers that we have right now, you have to say, with all of them, you should look again more carefully. What is the best distance at all? What is the best vaccine third?? For example, half a dose is sufficient? These are all things that you actually look at in studies. And I think we still have time at the moment to gather more experience.

Hennig: That means even with booster vaccination, which we’ve talked about so many times on the podcast, it may not even necessarily be a black and white decision, but one somewhere in between where you can still figure out if there’s a gray decision, with less vaccine, with a compromise.

Ciesek: Yes. Or boosting with a different vaccine, for example. So it really makes sense to always take the same one? We have talked about heterologous vaccination many times before. There may be other vaccines coming soon with the peptide vaccines as well. So that’s just not clear yet. What’s certainly coming to this as well is an update specifically for Delta.

That would be what makes the most sense to me personally speaking – waiting for an update like that to come along, which is just a better fit for the Delta virus for example. In contrast, now without risk factors and without great need to simply make the vaccination. And without there being enough data to support that.

Hennig: As far as the effectiveness of vaccination against delta is concerned, there have always been very different figures in circulation. You said it so well earlier, one study says "giddy up.", the other "hott". It’s not quite like that here. But there are numbers that give hope, how well the vaccination against Delta works, the unadapted previous vaccination. And there are numbers where you kind of say, again, this doesn’t look so good. What is the overall picture, if you now get an overview, where is the direction going??

Ciesek: Exactly. There are now a large number of studies that have investigated this. And the highest effectiveness is shown for example in a study in the New England Journal, which looked at symptomatic infections in the general population, at 88 percent. That is very good. In contrast, there are studies from Qatar, for example. This is a preprint. There it is still 53.5 percent. In another preprint from the USA, the figure is 42 percent. You always have to look at how these studies were actually conducted, whether they also cover asymptomatic infections or whether they only look at symptomatic or severe cases.

In principle, one can say that there is still good protection against severe courses, against symptomatic courses, which is again in line with the data that we discussed earlier. The protection against asymptomatic infections is significantly lower with delta. But that’s not so bad, to put it bluntly, if you have an infection that you don’t notice. So for you, it’s not too bad. If you have contact with the unvaccinated, it can be very unpleasant for the person.

Correlation between vaccination rate and childhood illnesses

Hennig: They said an infection that you don’t notice. Good cue for me – for an elegant segue to the next topic we want to talk about today. Children, as we know, often do not notice the infection, or at least they have a mild course. The idea takes hold again: In the case of children who, perhaps with bad luck, do not fare so well, the adults can possibly protect the unvaccinated children under twelve with their own vaccinations.

Now you see in the U.S. also the other way around with the delta variant that this can have a negative effect. Where the vaccination rate is very low. There are big differences in the different states in terms of vaccination readiness. Is it possible to pour that into a bit of a numerical risk estimate – that is, quantify: low vaccination rate, more people infected and therefore more children getting sick?

Ciesek: Yes, this is also broken down by the CDC in this journal, which they publish weekly. That’s quite interesting. They had 30.000 cases in August in the hospital, especially in Texas and Louisiana. And, of course, they say that compared to adults, children are significantly less affected. But that it has increased with delta and that you can’t ignore that. And, of course, you have to closely monitor how this develops. And that one must consider that children cannot be vaccinated so far and are therefore dependent on the protection of the community. That’s certainly one of the largest groups that relies on third party vaccination.

Increase in RSV cases in the U.S

It has to be said that there are bottlenecks in care in the USA, because of course they have a completely different health care system than we do. And there has still been an increase in RSV cases there. This is a virus that causes respiratory infections, which can be a huge problem especially in the first infection in infancy. At the moment, this is leading to a large number of children in the USA being hospitalized with a double infection, for example. And that even the American hospitals, children’s hospitals have asked that adults get vaccinated and wear mask to protect children.

What can be stated in any case is: the higher the vaccination rate in a state, the fewer children are inpatients in children’s hospitals. There are certainly other factors at play here in the U.S., i.e. other viral diseases that are more common now that measures are being scaled back, masks are no longer being worn. We have also discussed this before in a podcast. Of course, this is a common argument: yes, the kids in the U.S. are all much fatter. Clearly, there are perhaps proportionally more Adipositas there. But a problem is also that children often have worse controlled underlying diseases, for example asthma.

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