A pandemic six months later
Repeated infections, bad tests and a new quarantine
Sergey Dobrynin, Radio Liberty
How much better is the world prepared for this outbreak compared to spring? On the one hand, several vaccines are already undergoing clinical trials of the last, 3rd phase. The disease, its epidemiology and treatment have been studied much better than at the beginning of 2020. On the other hand, effective drugs have not been found, and the first cases of re-infection indicate that acquired immunity can only be a temporary weapon against COVID-19 and reduces the hope of group immunity.
Radio Liberty discussed poorly studied human immunity, questionable testing strategy for COVID-19, successes in the treatment of the disease and a new understanding of effective quarantine measures with Irina Yakutenko, biologist, scientific journalist, author of the book "The Virus that Broke the Planet", which is being prepared for publication by the ANF publishing house.
– About 9 months have passed since the first outbreak of COVID-19 in China, almost exactly six months since the announcement of the pandemic. Today we know much more about the disease and the virus than in the spring, we are much better equipped to fight the epidemic, but some new facts are alarming. Let's start with them: relatively recently, several cases of re-infection were well documented for the first time.
– One example of re–infection has been well documented so far - this is a man from Hong Kong who was infected for the first time in March, and the second time in August. Researchers from the Netherlands and Belgium have already said that they have been observing repeated infections for a long time, but did not rush to scientific publications because they were such curiosities, isolated cases. But since the media noise has started now, they will also gather and publish in the near future, so there will be at least three, apparently, publications about repeated infections.
So repeated infections are really possible. But we have already had 25 million cases, and so far we can say with some certainty about four cases of re-infection. Perhaps this is just a very rare story that is associated with some individual characteristics of immunity. This hypothesis is supported, for example, by the fact that the only well-documented patient with repeated infection had an atypical immune response, he did not have specific antibodies after the first infection. The second option is that this is a mass story, but immunity persists for at least 6-8 months, and we will see more massive re-infections later. Unfortunately, there are no fundamental reasons why mass re-infections should not happen.
In general, there are two points of view. The first is that COVID–19 is a respiratory infection, and for them, in general, re-infection is extremely characteristic, this applies to both flu and common colds. The usual coronavirus colds – you can get sick with them twice a season, as it turned out now that there is a reason to study it properly. The second point of view is that COVID–19 is a serious infection, and usually the more severe the infection, the less frequent re-infection occurs. But this is self-deception, because most coronavirus infection proceeds easily. Therefore, there are no fundamental prohibitions, and I would not be surprised if it turns out that re-infection is possible and this is a fairly common story. The good news is that, it seems, repeated illness is milder than the primary infection. A man from Hong Kong would not have known at all that he had been ill for the second time, they just took mandatory samples from him at the airport. There may be more re-infected now, they just don't have symptoms. So far, we do not see the worst option – a more severe course of infection with secondary infection, and this pleases.
– The issue of re-infection is important because it concerns our immunity to COVID-19. What exactly happened in this first well–documented case of re-infection - did the acquired immunity not survive for so long or did a new, roughly speaking, strain of the virus appear that he did not recognize?
– Good question. Indeed, there are two possible options: the first is that the virus changes and goes away from the immune response, so we get sick for the second time, and the second option is that for some reason the antibody titer quickly fades and memory cells also become so small that they do not have time to start the synthesis of a large number of antibodies against re–infection in time. This man from Hong Kong, on the one hand, had two different strains of the virus, they genetically differ from each other in many places. At the same time, he did not develop antibodies after the first infection, so it is difficult to judge exactly what happened according to this case. In fact, the pandemic has shown that we know very little about the immune response to colds – no one really bothered, since the harm from them is small. But ironically, it was the cold virus that caused the global pandemic.
– But in the case of COVID-19, do we at least partially have an answer? A few months ago we heard the bad news – antibody immunity after the disease drops rapidly, within 2-3 months. And then there was good news – but another branch of immunity, cellular, persists much longer. Now we know how they relate?
– We don't know. There is no mass screening for cellular response. It is made only within the framework of individual studies, and only antibodies are tested en masse. It is only known that a cellular immune response takes place, that it occurs in both symptomatic and asymptomatic, and even in those who do not seem to have been ill at all. This is an interesting story, that is, it is unclear whether they still suffered COVID-19 completely unnoticed, or whether cross-immunity with other coronavirus colds is somehow being developed. In a word, I repeat – we realized that this field is radically under-researched, including the ratio of cellular and antibody immune response. This is actually sad, because if we knew this, it would be easier to work on vaccines. Now, when creating them, they mainly pay attention to the antibody response, not least for technical reasons, because it is much easier to check. It is almost impossible to check the cellular response in tens of thousands of vaccinated people. I hope that after this epidemic, such a check will become a common practice.
– Another important news of recent times is that the PCR test, that is, the main analysis for COVID–19, turned out to be too sensitive in some sense. Some researchers claim that up to 70 percent of people with a positive PCR test actually have so little virus that they do not get sick themselves and are not able to infect anyone, which means they do not have to be isolated. How important is this discovery? Is there a pandemic on a smaller scale than we think it is?
– In fact, this is not a new discovery, it's just now written about it in the New York Times, and so among specialists, the excessive sensitivity of PCR tests has been discussed since about February. Proponents of this idea say that real–time reverse transcription PCR – the "gold standard" for detecting the virus today - is not really suitable for mass diagnostics. This is a very sensitive tool, it allows you to detect a very small amount of viral RNA. At the same time, studies say that if the scraping was diluted in a milliliter of solution and there are less than a million copies of viral RNA (they used to talk about 250 thousand, but now it is clear that we are talking about a million), then it is impossible to infect cells with this, and therefore a person who has such a number of viral RNA in the sample RNA is definitely not contagious. Infection of cells is generally an ideal situation for a virus, it is more difficult to infect a person than a cell. At the same time, the PCR test reveals somewhere tens of thousands of copies of RNA, that is, orders of magnitude less. Therefore, it is good for research purposes, but bad for diagnostics. Overly sensitive tests give a huge number of "unnecessarily positive" answers, which are useless for epidemiological purposes – to protect society from carriers that can infect others.
And this is just one of the problems with PCR tests. Another is that they are conducted in laboratories with specially trained personnel, logistics issues arise, because of which the results are received with long delays. For screening purposes, in order to isolate people, for example students who have come to school and may be contagious, this is not suitable. And the third drawback – they are terribly expensive. The price fluctuates around 30-50 dollars per sample, that is, even the richest countries can hardly afford to test, for example, all schoolchildren and students every day.
All this suggests that using a PCR test as a basis for mass diagnostics is a bad strategy, especially if we want to abandon restrictive measures as soon as possible without the threat of a sharp increase in the number of cases. Therefore, since February, a number of scientists, primarily Michael Mina from Harvard, have been saying that the tests should be different: these should be quick tests that give an answer within 15 minutes. They can be held in the morning before school or before work. These tests are not so sensitive, they identify only those who have a lot of viral RNA – and who are really contagious. There are two types of such tests, one is strips like pregnancy tests, these are tests for virus antigens (that is, they directly determine the presence of viral particles in the sample), the second is a test developed by the American company Abbott, it is based on the so–called isothermal loop isomerization (it determines the presence of viral RNA). Both give results within 15 minutes. What is most interesting, the tests have been developed for a long time, but until now the regulators paradoxically "wrapped" them due to insufficient sensitivity.
– One of the features of the current stage of the pandemic: the global number of new cases of infection is not decreasing, in some countries, such as Russia, it has recently started to grow again – according to official statistics. At the same time, hospitals generally do not have such a catastrophic workload as in the first months of the pandemic. What could this be related to?
– The first factor is the number of tests. At the beginning of the epidemic, few tests were done everywhere, including in the United States, where a sharp increase in the number of new cases began around mid-June. Previously, mostly symptomatic people were tested, that is, people who are more likely to be hospitalized later, therefore, the ratio of the number of detected cases of infection to the number of hospitalizations was high. Now people without symptoms are being tested quite widely. There are fewer of them who will have a severe development of the disease and who will go to the hospital, so the ratio is smaller. But this does not mean that we have learned how to prevent a person from getting into the hospital – no, unfortunately.
– But for those who have already been admitted to hospitals, is the prognosis better? Over the past months, there has been an understanding of which treatment protocols are effective, which medications make sense to use?
– Yes and no. Indeed, the chances of a person who now catches SARS-CoV-2 getting out of the hospital alive are much higher than they were at the beginning of the epidemic. Not only because in the beginning in some countries, like in Italy, the health systems were overloaded. We have a much better understanding of the general course of infection, that is, how it develops in different cases, in mild, in severe, in critical. And despite the lack of real drugs with proven good efficacy against the virus itself, we nevertheless understand how to treat patients with a disease of varying severity. We can predict who needs to be given increased attention: these are, in particular, elderly people, patients with various concomitant diseases, cardiovascular, pulmonary, diabetic and obese, to a lesser extent cancer patients. In the early stages of the disease, we are practically powerless, antiviral drugs have not shown any effectiveness. All that more or less works is remdesivir, and it is already used by those who need oxygen support, as well as dexamethasone and other steroids. According to the latter, not many good clinical studies have been conducted, but judging by the accumulated experience of many doctors, steroids help patients who have started hyperactivation of the immune system. It is she who foreshadows a cytokine storm, is the main driver of all complications, it is from her that all these troubles come: thrombosis, organ failure, ARDS. And according to the already well-known parameters, we can see that this process has started, and, for example, start giving patients steroids.
In fact, only these two drugs have proven effectiveness, but they make it much better to stop the development of the most dangerous, last stage of the disease. Plus, we know what complications occur most often, and we are able to cope with them, including prophylactically. For example, the same microthrombosis: it can cause stroke, heart attack, pulmonary embolism, deep vein thrombosis, so patients are often given anticoagulants today.
So really, in cases when the disease reaches a moderate and severe stage, we are much better prepared. But nothing new has been invented for the treatment of the early stages. The worst thing is when, as in Russia, pseudoscientific drugs are prescribed in the early stages, which not only have not been proven effective, but have been proven ineffective, such as hydroxychloroquine. People who recover perfectly without any medications are prescribed hydroxychloroquine, prophylactic antibiotics, which are not done anywhere else, and other heresy. But I must say that in the latest version of the Russian clinical guidelines for the treatment of COVID-19, hydroxychloroquine was canceled in the early stages. But they added preventive arbidol! However, to be honest, Russia is not alone in this approach – in the USA, plasma therapy was approved without any evidence.
– Recently, schools, kindergartens and universities have opened in many countries after a break. Different methods of control are used everywhere, sometimes quite bizarre, as in Moscow, where lessons begin in different classes at different times. But all of them are unlikely to be able to prevent new outbreaks of the disease, which means that quarantine measures will probably have to be introduced. Do we know now, six months after the start of the pandemic, which restrictions work better and which ones work worse, how the minimum necessary quarantine kit works?
– Yes, we know much more than we knew in the spring, and even if there is a "second wave", that is, the pandemic will start to get out of control again, I hope that there will be no more big "closure". Now we understand that universal quarantine is an excessive measure that can be more dangerous than the disease itself. By analogy with other diseases, it was initially believed that the transmission of the virus through surfaces makes a significant contribution to the overall morbidity, that you need to wash your hands a hundred times a day for at least 20 seconds. Now we understand that this is not the most important way of infection, that is, there are no proven cases of infection, for example, through a milk carton in a store. There are two main ways: airborne and aerosol, they differ in the size of droplets. Accordingly, knowing this, we understand that adequate measures are masks and distance.
Masks delay most of the droplets, knock down a little bit of the aerosol distribution flows, plus much less is inhaled. The distance is because even though the droplets scatter, and the aerosol cloud spreads far, but the farther you are, the less it reaches you. Another factor is the contact time. If you pass quickly in a mask at a great distance from the carrier of the infection, the chance of getting infected is small. Finally, we know that this is a disease characterized by clustering, that is, people infect each other unevenly. Most carriers do not infect anyone or one or two people with whom they communicate especially closely. But there are those who manage to infect dozens of people at once, such carriers are called super-distributors (super-spreaders). Such clustering – when it is clear in which clusters the infection is particularly rapid – allows for better control of the epidemic. Obvious clusters are, for example, bars, clubs where people stay for a long time, kiss, hug, sing songs, droplets fly in all directions, where a super–distributor can infect many people at once. And in the subway, not at rush hour, there is just not a very high risk of infection if people are wearing masks and not very close to each other.
– So it makes sense to close bars and clubs, but not the metro?
– The main thing is to eliminate the situation of cluster formation, when a lot of people in a close room communicate with each other for a long time. And in this sense, for example, demonstrations in the fresh air are not so dangerous, but with the lessons of the choir circle, in which there are only 10 people, but they sit for two hours in a cramped room and without masks, it is worth waiting. As for schools, this is, of course, a very important risk factor. At first, there was a myth that in the context of COVID-19, the spread of infection is not associated with children, unlike many other respiratory infections. Now there is an understanding that this is most likely not the case, it just so happened that almost immediately the children were quarantined. When the epidemic came to Europe in earnest, the children first had school holidays, then they were quarantined in most countries, then they had holidays again. Now that children are returning to normal social life, experts expect that there will be serious outbreaks in schools, both among parents and teachers. And the children themselves will get sick and end up in hospitals. And we will have to decide whether to close kindergartens and schools again, or use some new rapid testing system like the one I described above.
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