In many young adults, a Sars-CoV-2 infection runs without problems, and often it even goes unnoticed. Researchers are using recruits in barracks in the United States to study whether these people are protected from being infected again.
A survived infection with Sars-CoV-2 does not fully protect young people from being infected again. This is based on an observational study of more than 3,000 members of the US Marine Corps, most of whom are male, and who were between 18 and 20 years old at the time of the investigation.
The recruits who wanted to complete their six-week basic training at the “United States Marine Corps Recruit Depot Parris Island” all had to stay in quarantine for two weeks to protect themselves from infection. During this time, three PCR tests were carried out on them. If these were negative, the people tested were still sent to a monitored quarantine for two more weeks before they were allowed to enter the barracks premises. During this time, the blood of the prospective soldiers was tested for antibodies.
With these security measures, those responsible at the barracks tried to keep Sars-CoV-2 away. However, there were many new infections and even some reinfections among the recruits. In the study period between May and November 2020, the researchers led by Professor Stuart Sealfon from the Icahn School of Medicine on Mount Sinai saw re-infection in 19 of 189 of the people examined who were previously infected with Sars-CoV-2. In comparison, there were 1079 new infections in a total of 2247 recruits who were not previously infected. The figures show that almost half of the young men were infected before starting their training in the barracks, despite all the safety measures.
Reinfections likely in young people
The researchers believe that the risk of reinfection they found applies to many young people, but that the reinfection figures of almost 10 percent in the barracks, where many young people live in confined spaces, are not transferable to life outside of military stations . It is likely that the special living conditions on a military base with close personal contacts would have led to higher total infection rates than elsewhere, write the researchers, whose results were published in the journal “The Lancet”.
However, the figures also provide information that a survived infection does not leave a safe immunity in younger people. The researchers are also unable to provide any information about the duration of a possible immunity, since the time of the first infections was not known when they examined them, as these were usually without symptoms. However, the results provide some information about the secondary infections.The PCR test was only positive after seven days in 32 percent of the newly infected. Among the first infected recruits that was 47 percent. In addition, symptoms only occurred in 3 percent of a second infection. In the case of new infections, however, symptoms occurred in 32 percent.
Not enough antibodies
The researchers believe that a weak immune response in the body is likely to be the cause of secondary infections. Recruits with a low number of antibodies against the virus protein were just as frequently re-infected as recruits without prior infection. In addition, the serum of the recruits who were infected a second time was also less able to prevent the infection of cells in laboratory tests, the researchers further report.
The milder second infection was also associated with a lower viral load, which in turn indicates a lower probability of transmission. Nevertheless, according to a press release, Sealfon emphasized that young people should be vaccinated for their own protection and that of others, even if they already had an infection with Sars-CoV-2.
A new model records glycan molecules, the movements of which shield a large part of the spike protein from the immune defense cells
A key feature of Sars-CoV-2 is its spike protein, which extends across its surface and enables it to target and infect human cells. Much research has resulted in detailed static models of the spike protein, but these models do not capture the flexibility of the spike protein itself, nor the movements of the protective glycan chains of the sugar molecules that coat it. A new, detailed model of the surface of the Sars-CoV-2 spike protein, which was created by scientists at the Max Planck Institute for Biophysics in Frankfurt am Main, shows previously unknown weaknesses that could lead to the development of vaccines.
To aid vaccine development, Mateusz Sikora and his colleagues wanted to identify new potential target sites on the surface of the spike protein. To do this, they developed molecular dynamics simulations that capture the complete structure of the spike protein and its movements in a realistic environment.
These simulations show that glycans on the spike protein act like a dynamic protective shield that helps the virus evade the human immune system. Similar to car windshield wipers, the glycans cover almost the entire spike surface by flapping back and forth, even if their coverage is minimal at all times.
By combining the dynamic spike protein simulations with further bioinformatic analyzes, the researchers identified places on the surface of the spike proteins that are least protected by the glycan shields. Some of the sites discovered have already been identified in previous research, but some are new. The susceptibility of many of these new sites was confirmed by other research groups in subsequent laboratory experiments. “We are in a phase of the pandemic that is constantly being changed by the appearance of new variants of Sars-CoV-2, with the mutations particularly concentrated in the spike protein,” says Sikora. “Our approach can support the design of vaccines and therapeutic antibodies, especially when established methods fail.” The method developed for this study could also be used to identify potential vulnerabilities in other viral proteins.
The „No Covid“-Initiative has in an opinion the Federal government urged to act after the withdrawal of the Corona Easter rest. “Which steps should be taken instead to bring the infection process under control remained open,” the initiative announced on Thursday.
In addition, measures such as corona tests, contact tracking and vaccinations have “not been used effectively”, so that the country is “heading into a third, all projections very violent, pandemic wave”.
To the To reduce the number of infections, from Maundy Thursday up to and including Easter Monday, economic, public and private life in Germany should be severely shut down. After the Easter rest was surprisingly canceled on Wednesday, it is not clear in some federal states whether the contact rules of the emergency brake apply over the holidays. “Against this background, we urgently recommend a change of course towards a strategy of low incidence,” demanded the initiative in the statement.
Accordingly, the goal should be the Press the R value below one and hold it there, “Because only this offers a sustainable and structured opening perspective”. According to the RKI management report on Wednesday evening, the nationwide seven-day R-value was 1.00 (previous day 1.04). This means that 100 infected people theoretically infect 100 more people. The value represents the occurrence of the infection 8 to 16 days ago. Researchers from several disciplines are involved in the “No Covid” initiative. The initiative is not identical to the “Zero Covid” groupwhich calls for a far-reaching, longer and Europe-wide lockdown.
Berlin – An international research team led by structural biologist Andrea Thorn has been trying since the beginning of the pandemic to decipher individual protein components of Sars-CoV-2 as precisely as possible – among other things, so that drug developers around the world can search for remedies. But there is still a lot that remains to be clarified.
Berlin newspaper:Frau Thorn, wWhy is it so important to structurally examine the coronavirus?
Andrea Thorn: The coronavirus is made up of molecules. Understanding their structure exactly and having models of these molecules is necessary in order to find out how Sars-CoV-2 works in the first place: If, for example, the virus takes over a human cell and causes it to produce more viruses, then every single step has been taken made from a protein molecule. And disabling these protein molecules therefore means stopping the infection. But you can only do that if you know it very well: you have to understand the lock in order to be able to build a key. We are improving the molecular models of the coronavirus and making them publicly available online so that drug developers can specifically search for active ingredients that match the proteins and block them, for researchers at universities and also in the pharmaceutical industry.
You head the “Coronavirus Structural Task Force”, an international network of experts in the field of structural biology. How did it come about?
In February 2020 I looked at molecular models of the Sars coronavirus, which had already triggered a pandemic in 2002 and is very similar to the new coronavirus, and found out that more biological knowledge can be extracted from the structures with today’s methods. With this knowledge, I started a month later, together with my work group and international colleagues, to systematically examine the structures from Sars and the new coronavirus. From then on we have grown steadily. Today we’re a pretty diverse group with 27 team members in nine time zones. That was quite unusual for a research project: no professor at the top, at the beginning without research funding – we are now funded by the Federal Ministry of Research – and all results go online immediately. But we were able to use our knowledge to fight the pandemic – and that was the reason we joined forces.
So the pharmaceutical companies don’t need approval from the task force?
No. We want drug developers from the Philippines to Brazil or India, all over the world, to have access to our data.
What does Sars-CoV-2 look like in simple terms?
The coronavirus is not completely round. It’s like a soap bubble in constant motion – wobbly, if you will. The outer layer is thin, soft and made up of fatty acids that are chemically similar to soap. Because of this, soap can completely dissolve the shell of the virus – provided that the hands are washed long enough. The outer layer is covered by so-called spines, which allow the virus to penetrate into lung cells, for example. But what you call a virus – that is actually just the form of transport, the “virion”. Inside, it carries genetic material for a total of 28 protein molecules, most of which are first built in the host cell in order to transform it into a virus production facility.
All this is difficult to imagine for laypeople.
Many people still believe that viruses cannot be made visible. They may even fail to realize that the colored images shown in the media are images of the virus. The virus and its danger are not visible. The people do not see the many dead, they do not see the completely overloaded intensive care units because there is a ban on visits. This is also one of the reasons why we also made and printed a 3D model of the virus so that we can make the danger a bit more tangible.
How do you decipher the molecular structures?
The entire virus is not measured, but individual molecules. Structural biologists are looking for one of the 28 different proteins that make up Sars-CoV-2, for example the spikes on the surface of the virus. The molecule is not dangerous on its own, which makes work a lot easier. Genetically modified bacteria produce many copies of this molecule. Then there are two options: Either we take the thinly applied sample, cool it down to very low temperatures and put it under an electron microscope. A so-called transmission image is created, a negative image of the virus protein. From these individual snapshots of the molecule you can make a three-dimensional picture and use it to build a model of the molecule.
The other option is to crystallize the egg white. The crystals are a tenth of a millimeter in size and consist of thousands of identical protein molecules. This crystal is then measured using X-rays at a so-called synchrotron, a particle accelerator, such as Bessy II in Berlin. These data also make it possible to build a three-dimensional model of the molecule from which the crystal was made.
What role does the task force take on in these research steps?
We review and improve the models that were generated with the measurement data. My team members sit in front of a 3D monitor wearing special glasses and look at every single atom. Sometimes we build the models from scratch. Of course, you don’t just have to orientate yourself on the measurement data, but also position the individual atoms in a chemically sensible way, at the correct distance from one another: It’s a bit like how computers play.
How long do the individual steps take?
The multiplication in the bacterium can take one to 36 months with the purification until it works. The egg whites crystallize in one to 24 months. The measurement in the synchrotron takes about three minutes. The data acquisition and the assembling of the structures with the special glasses take a week to four months.
That means your team is responsible for the 3D modeling of the structures?
I agree. With 10,000 or more atoms per molecule, mistakes can easily happen – especially under the pressure of a global pandemic. These mistakes can doom the development of a drug from the outset. That is why we have to find and fix the errors beforehand. This is also very important for the biological questions about the virus. We are not the pioneers who will measure the structures, nor are we the ones who will find the medicine. We can enable and facilitate it and ensure that everything that is possible is really extracted from the experimental data.
How big are the gaps in knowledge about Sars-CoV-2 today?
A lot has been discovered in the past year. Researchers around the world have worked together – so do we! But of the 28 molecules of the virus, only 17 have so far been successfully measured. And even about these 17 we know we don’t know enough. Its a lot to do.
Is there anything that amazed you in the course of your corona research?
At Sars, people got very sick very quickly and went to the hospital soon after their infection. Once they were hospitalized, they could no longer infect anyone – that is, the outbreak could be more easily contained. With the novel coronavirus, around 15 percent of people develop no or few symptoms, but are still contagious. So the coronavirus is particularly dangerous because it doesn’t make you sick that badly. That sounds paradoxical, but of course it means that many more people can become infected and, in the end, there are many more deaths.
What do you know about the molecular details of virus mutants, new virus variants?
So far there are not many structures – the determination takes a few weeks or months – but these structures can be simulated very easily on the computer, as only a few of the thousand atoms in the molecule change.
What would have happened if scientists hadn’t stopped researching the virus after the Sars pandemic from 2002 to 2004?
The studies never stopped entirely. There were researchers like the Lübeck biochemist Rolf Hilgenfeld, who did corona research for many years in a quiet little room – with one and a half positions and small budgets. We owe the knowledge at the beginning of the corona pandemic to them. But yes, after the Sars pandemic, research declined significantly and was no longer funded as much. With Sars-CoV-2 it becomes clearer than ever: It is worthwhile to invest in research projects in the long term, and indeed for longer than one legislative period. If Sars research had been carried out continuously, we would have had a lot more knowledge about coronaviruses at the beginning of the pandemic. That would have been a huge benefit and I hope we are better prepared for the next pandemic.
Is it possible that SARS-CoV was in Europe already in November 2019? According to data from a study published in the “European Journal of Epidemiology” this idea does not seem far-fetched.
The work, carried out using serum samples collected routinely from 9,144 adults from a French general population cohort (Constances), has identified 353 participants with a positive anti-SARS-CoV-2 IgG test.
Nothing anomalous if it weren’t for the fact that those samples were obtained between 13 between November 2019 and January 2020 and confirmed by antibody tests, a month before it is officially declared the first epidemic outbreak in the Chinese city of Wuhan.
The CDC recommends that teachers give priority to vaccinations and has issued guidelines on how schools can reopen. The CDC does not speak out clearly in favor of school openings, but states that the available data no connection between classroom teaching and high infection rates was shown would have.
The guidelines include the correct wearing of masks, distances of two meters if there are high numbers of infections, strict classroom cleanliness, regular tests and quick contact follow-up.
Many students in the United States hadn’t been to school in almost a year.
Representative of Czech commuterswho work in the Federal Republic are concerned about the planned ones stricter entry rules to Germany. The federal government in Berlin has declared the neighboring country to be a virus variant area. Jan Triska from the Czech Pendlervereinigung APCR on Friday called for financial help for those workers who are no longer allowed to drive across the border into Germany or who are overwhelmed by the situation. He pointed out that commuters in Germany would pay taxes and social security contributions.
“It shouldn’t be that you end up on the street from one day to the next,” Triska told the German Press Agency. He expects that only medical personnel and employees of the critical infrastructure will be allowed across the border. The deliberations on the details are still ongoing in Berlin.
According to Triska, even a daily test requirement would be a great additional burden. “Eight hours at work, one hour on the way there and back and then the waiting time in the test center,” he listed. That overstrains the strength of the people who then no longer have time for their families. It is estimated that driving 35,000 to 60,000 Czechs to work in Germany. Because many of them work in the hospitality industry, which is closed due to Corona, it could currently be significantly less.
Representative of Czech commuterswho work in the Federal Republic are concerned about the planned ones tightened entry rules to Germany. The federal government in Berlin has declared the neighboring country to be a virus variant area. Jan Triska from the Czech Pendlervereinigung APCR on Friday called for financial help for those workers who are no longer allowed to drive across the border into Germany or who are overwhelmed by the situation. He pointed out that commuters in Germany would pay taxes and social security contributions.
“It shouldn’t be that you end up on the street from one day to the next,” Triska told the German press agency. He expects that only medical personnel and employees of the critical infrastructure will be allowed across the border. The deliberations on the details are still ongoing in Berlin.
According to Triska, even a daily test requirement would be a great additional burden. “Eight hours at work, one hour each on the way there and back and then the waiting time in the test center,” he listed. That overstrains the strength of the people who then no longer have time for their families. It is estimated that driving 35,000 to 60,000 Czechs to work in Germany. Because many of them work in the hospitality industry, which has been closed due to Corona, it could currently be significantly less.
The majority of the population can produce neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe cases of coronavirus disease 2019 (covid-19). This is supported by a study published today in the journal “PLoS Pathogens.”
In addition, the work coordinated by Michael Mor of the University of Tel Aviv (Israel), supports the use of antibody combination therapy to prevent and treat COVID-19.
Neutralizing antibodies are believed to specifically target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein they are essential to control the virus.
So far, researchers have detected antibodies RBD specific neutralizers in convalescent patients, those who have recovered from covid-19. Some of these recovered patients tend to have robust and long-lasting immunity, while others show a progressive decrease in their neutralizing antibodies.
However, the factors associated with an effective and long-lasting antibody response are not yet clear.
To delve into this gap in knowledge, the researchers used molecular and bioinformatics techniques in order to compare the responses of the B cells in eight patients with severe covid-19 and 10 individuals with mild symptoms, 1.5 months after infection.
The results showed that the patients who were sickest presented higher concentrations of specific antibodies against RBD and further expansion of B cells.
“Among the 22 antibodies cloned from two of these patients, six exhibited potent neutralization against SARS-CoV-2,” they write in the article.
Based on data from bioinformatics analysis, it is suggested that most people would be able to produce neutralizing antibodies against SARS-CoV-2 in severe cases of COVID-19.
The researchers verified that the combinations of different types of neutralizing antibodies completely blocked the spread of the live virus.
According to the authors, these antibody cocktails should be tested in clinical settings as a useful means of preventing and treating COVID-19. And they write, even with a vaccine available, “arming physicians with specific therapies against SARS-CoV-2 is extremely important.”
Researchers believe that neutralizing antibody combinations represent a promising approach towards the effective and safe treatment of severe cases of COVID-19, «especially in the elderly population or people with chronic diseases, who will not be able to produce these antibodies so easily after infection or vaccination».