SARS-CoV-2 mutated: What we know about the Corona variants
In recent weeks, there have been repeated reports of new variants of the previously known coronavirus from Great Britain, South Africa and Japan. Should we be afraid of these mutations? Prof Dr Matthias Stoll, MHH infectiologist, explains.
Status: 15. January 2021
Why are these mutations currently attracting so much attention?
Prof. Stoll: The press reports about variants of the SARS-CoV-2 virus suggest that this phenomenon is something new, unexpected or threatening for SARS-CoV-2. What is new, however, is simply the high level of public awareness since the first press announcements about a new variant that has been increasingly seen in the south-east of the UK. This increased perception is based on two features: Firstly, sequencing of genetic material from SARS-CoV-2 isolates - which was based solely on scientific grounds - had been carried out about 100 times more frequently in the UK than in Germany and other regions up to that point. This explains the - incidentally false - perception that it would be a SARS-CoV-2 variant only present in Great Britain or - also false - found there for the first time. Secondly, the variant was announced very effectively in the press by British Prime Minister Boris Johnson, combined with the claim that it would be a more contagious and dangerous virus than the other SARS-CoV-2 variants - and that this variant would explain the rampant infection figures in the UK. At least this last point cannot be true. For one thing, only a small proportion of COVID-19 cases are caused by this so-called variant B 1.1.7 in the UK, and for another, the wave of infections there is mainly due to public health measures.
Isolated cases of these mutations have now also been registered in Germany. Should this worry us?
Prof. Stoll: Cases of B 1.1.7 had already been described in other countries well before it appeared in the UK. One of the first cases described in Germany was treated in November at the MHH on one of the COVID-19 wards and his virus was sequenced by the MHH virology department. Its chain of infection could be traced back to Great Britain. Serious scientific investigations are currently underway in various places to clarify whether the virus is actually more contagious or more dangerous.
How do these mutations occur? Will there be more mutations?
Prof. Stoll: The success model of SARS-CoV-2 and most other viruses in the early phases of a pandemic or epidemic is based on spreading as quickly as possible and optimising its adaptation to the host with a particularly high multiplication and mutation rate. As early as May 2020 - i.e. a few months after the first cases in Wu Han - it was described that worldwide - and partly simultaneously - a mutation of the amino acid at position 614 (D614G) of the SARS-CoV-2 spike protein occurred and partially completely displaced the original virus within barely three months. The researchers were able to show that the 614G variant replicated faster than its viral ancestor with D614.
How do the three variants differ?
Prof. Stoll: All variants have mutations in the spike protein. The spike protein is the tip of the "crown spikes" that gave the "Corona" virus its name. With this protein, the virus binds to our body cells via the ACE2 receptor present there.
I don't know many more details about the Japanese variant, which has only been found in four people so far. The variants from South Africa and Great Britain have a lot in common: both variants have a mutation at amino acid 501. This mutation (N501Y) was already described half a year ago in Beijing and had attracted attention in animal experiments because it was the only variant of SARS-CoV2 that could also infect experimental mice. The idea that the virus could decisively change its contagiousness at this point is therefore obvious. All other statements about an increased risk of disease or death are so far completely speculative.
Are the mutations more dangerous than the known coronavirus?
Prof. Stoll: We don't know yet. Scientific research is in full swing, but it will take some time. Our society is finding it increasingly difficult to tolerate this state of uncertainty in times of delay-free digital communication. I am somewhat unhappy that such far-reaching and dubious speculation is currently taking place. It is quite possible that the mutations have no significance at all for the intensity of the disease.
If this is not the case, we should ask ourselves why the mutations in a pandemic that has been going on for a year should now (only) bring an inevitable catastrophic turn to mass illness and more severe courses. The experience from the co-evolution of (new) pathogen and host is generally like this: The pathogen manages to infect its host more and more effectively. There is evidence of this with D614G and N501Y. At the same time, however, it is necessary for the virus to keep its host infectious as effectively as possible and for as long as possible. This, however, means precisely the opposite of severe diseases, which are characterised by strong defence reactions and consequent lung failure and premature death. Both sides thus find a - more or less - "peaceful" coexistence. This assumption could be supported by observations that the new virus variants possibly spread more quickly among children and adolescents than the previously predominant variants. Young people have also been comparatively less severely ill with SARS-CoV2 than older people. So what we are seeing may be the beginning of a good development for us humans.
What does the occurrence of mutations mean for vaccination protection, do we need new vaccines?
Prof. Stoll: So far, we can be confident that the vaccines currently in use also cover the virus variants currently reported in the press, because these lead to very many immune responses against presumably all important antigen sections of the spike protein. It is then not a matter of a single amino acid exchange. If the vaccines should lose their effectiveness due to more and more mutations, the mRNA vaccines in particular offer the comparatively simple possibility of adapting the vaccine. The technique of mRNA vaccination has been developed and optimised precisely for this purpose - the constant adaptation to changing tumour antigens.
MHH starts Corona vaccination of employees
Vaccination centre has started work / Even those vaccinated must strictly adhere to hygiene rules
Status: 07 January 2021
On Thursday morning, the time had come: Hannover Medical School (MHH) started to vaccinate its employees against the SARS-CoV-2 virus. Dr Thomas Rebe, head of the company medical service, was the first MHH employee to vaccinate Farah Demir, a nurse in intensive care unit 14 for COVID 19 patients. The second to receive a vaccination was Martina Toussaint, head of nursing at the Central Emergency Department, with the COVID 19 mRNA vaccine from Biontech/Pfizer. MHH President Professor Dr Michael Manns is glad that the vaccinations could start today: "This is a good motivation for the further commitment to our COVID-19 patients - but also for all other patients at MHH."
"I'm thrilled that the vaccinations are already starting," said intensive care nurse Farah Demir, "I actually didn't expect it until later." Her colleague Martina Toussaint from the Central Emergency Department is also happy about the vaccination start. "The willingness to vaccinate is very high in the emergency department team," she said, "because we see the consequences of the disease in our patients."
MHH had received a shipment of 975 doses of the vaccine, with the trade name Comirnaty, on Wednesday morning. Pneumologist and acting vice-president Professor Dr Tobias Welte explained that in allocating the vaccine, MHH strictly adheres to the prioritisation plan as stipulated by the Federal Ministry of Health. "The first to be vaccinated are employees with the highest priority, i.e. colleagues who deal with COVID-19 sufferers first." Welte stressed that "this is a safe vaccine", but that vaccination is voluntary.
The MHH has established its own vaccination centre. The Centre for Information Management has developed its own app to handle the vaccinations. Today, Thursday, and Friday, 50 employees each will be vaccinated first, and the other doses of the vaccine will be administered next week.
Professor Welte reminded all those vaccinated to continue to strictly observe all hygiene rules. "The first vaccination only offers a very low level of protection. In addition, we currently do not know whether vaccinated people can also spread the virus - any studies on this are still lacking," said the pneumologist.
Corona vaccine arrives at the MHH
Vaccination centre starts work on thursday / Even vaccinated patients must strictly observe hygiene rules
Status: January 6 2021
It was an inconspicuous package that arrived well-guarded at Hannover Medical School (MHH) on Wednesday morning. The contents were 975 vaccine doses of the COVID-19 mRNA vaccine from Biontech/Pfizer. The head of the MHH pharmacy, Dr Heike Alz, accepted the precious cargo with her colleague specialist logistician Kai-Marcus Negelen. "I am glad that the first employees of the university can already be vaccinated tomorrow, a good motivation for the further commitment to our COVID-19 patients - but also for all other patients of the MHH," emphasised MHH President Professor Dr. Michael Manns.
The pneumologist and acting vice-president Professor Dr. Tobias Welte adds that this will be done strictly according to the prioritisation plan in accordance with the specifications of the Federal Ministry of Health. "First of all, employees with the highest priority are vaccinated, i.e. colleagues who have to deal with COVID-19 patients. These are mainly employees from the emergency room and intensive care units who want to receive such a vaccination." The MHH has set up its own vaccination centre, he said. Dr Bastian Ringe from the MHH's COVID-19 task force explains that the first 50 employees will be vaccinated on Thursday and Friday respectively, and the other doses of the vaccine, with the trade name Comirnaty, will be vaccinated next week.
Professor Welte reminds all those vaccinated to continue to strictly observe all hygiene rules. "The first vaccination only offers a very low level of protection. In addition, we currently do not know whether vaccinated people can also spread the virus - any studies on this are still lacking," says the pneumologist.
Corona pandemic: MHH is a safe place to be
CoCo study: Next step is to investigate immune response after Corona vaccination.
Status: January 4 2021
Since the start of the Corona pandemic in Germany in March 2020, a research team from the MHH Department of Rheumatology and Immunology has been investigating in the CoCo (COVID-19 Contact) study how frequently SARS-CoV-2 infection has occurred among healthcare personnel. This was done by testing blood for antibodies to SARS-CoV-2, which indicates an infection has occurred. "Above all, we wanted to know how many participants had fallen ill without noticing it," says study leader Professor Dr Georg Behrens.
The reassuring results: There were far fewer infected than feared. Antibodies against SARS-CoV-2 could only be detected in about one per cent - a very low infection rate compared to the population of the Hannover Region. Only two of the more than 1,250 people tested had become infected by November without knowing it. Therefore, the fear of infecting oneself in the clinic is largely unfounded. And this is not only due to the relatively low number of COVID-19 patients so far. The clinic staff themselves also make a decisive contribution by obviously working responsibly and observing the hygiene regulations.
More than 1,000 employees participate in the CoCo study
The MHH is one of the first institutions nationwide to regularly test doctors and nurses from routine clinical and emergency care of COVID-19 patients. "We tested blood samples from more than 200 participants weekly at first, then monthly, and at the same time recorded possible symptoms with the help of questionnaires," explains Anne Cossmann, a doctoral student at the clinic and one of the organisers of the study. A logistical feat, because due to the distance rules, the participants could not be ordered centrally to take blood samples. "But since they are all medically trained, fortunately they took the blood samples themselves, we had, so to speak, all kinds of little study centres on campus," says study director Behrens. In the meantime, another 1,000 volunteers have been recruited and will be tested every six months. The interest in the CoCo study is enormous. "We are grateful for the willingness to participate, but unfortunately we cannot include any more interested people," says Professor Behrens.
The next step is to investigate vaccination protection
Now the study is entering a new phase, as vaccinations against SARS-CoV-2 will start soon. The next goal is to investigate the immune response triggered by this. "We have sent out questionnaires in advance to our participants about their possible participation in the vaccination. Based on the responses, we assume that 70 to 80 percent will be immunised against the Corona virus," estimates Professor Behrens. This leads to the question of how strongly the vaccinees respond to the vaccine, how many antibodies they form and how long the vaccine protection lasts. But participants who do not want to be vaccinated will also continue to be tested within the CoCo study. They will find out the results on a website set up especially for the clinical trial. "The site is a kind of communication platform for news, background information and diagrams," explains Anne Cossmann. The participants can log in with a personal password, ask questions and retrieve their study results - all pseudonymised and in compliance with data protection regulations.
What we now know about the COVID-19 long term sequences
Status: December 15 2020
Prof. Dr. Tobias Welte, pulmonologist and acting vice-president of the MHH, clarifies the status regarding the long-term consequences of COVID-19 diseases.
What are the complaints of those affected?
In the post-COVID-19 outpatient clinic of the MHH there are many people who suffer from symptoms after surviving an illness. But one must differentiate here. On the one hand, there are people who have been treated in the intensive care unit of the hospital due to a serious COVID-19 disease. These people do not leave the hospital without complaints because they sometimes had to be ventilated for weeks. But there are also patients who were only slightly ill and who report to the COVID outpatient clinic with complaints afterwards.
The complaints can also be subdivided. On the one hand, people complain about shortness of breath. The MHH physicians find that they have changes in the lungs, but also in the heart. For example, the pumping capacity of the heart muscle or the heart rhythm has changed. But these are the fewest cases. In addition, patients with chronic diseases - especially of the kidney and liver - can suffer permanent deterioration. Many more patients, however, have the so-called fatigue syndrome, a kind of fatigue syndrome. This manifests itself in exhaustion, insomnia, concentration problems, reduced performance and lack of drive.
How can these complaints be treated?
The organic diseases of the lungs and heart, for example, can be specially treated. There is no special therapy for the neurological symptoms - the fatigue syndrome and also loss of the sense of taste and smell. At the MHH, we try to provide targeted help with physiotherapy, respiratory therapy and neurocognitive training, depending on the type of complaints. If the sense of taste or smell is lost, training of these senses is also possible.
Those affected regularly visit the post-COVID outpatient clinic for weeks and months, and the doctors observe very clearly that the complaints diminish over the course of time and that people are getting better and better.
Is there an explanation for these neurological symptoms?
The fatigue syndrome is not new. It is known in connection with other infectious diseases such as Pfeiffer's glandular fever, in neurological diseases and also in the lung area. Presumably, the disturbance of the nerve muscle tissue plays a role in triggering this syndrome.
The olfactory disorder, on the other hand, has already been very well analyzed. Here, the corona viruses attack the olfactory cells, i.e. the cells responsible for the sense of smell. The damage can have different effects: If only the cells are affected, the disorder quickly recedes. However, if the supplying nerve is affected, it can take a very long time until the sense of smell is functioning again.
How many people suffer from long-term effects?
A rough estimate is that two to three percent of COVID-19 sufferers develop a pronounced post-COVID syndrome. There will probably be far more people who have slight limitations after the disease. But these people do not report it because they do not suffer from it in everyday life.
In principle, anyone who has been ill once can develop such long-term consequences. Whether the individual notices it very strongly or not at all also depends on his or her original physical condition and fitness before the illness. A competitive athlete notices even a slight limitation of his fitness very quickly and clearly. Someone who is rather motionless in everyday life does not notice the consequences so quickly. This could be the reason why younger, fit people in particular tend to suffer more, although they do not fall ill more often.
Vaccine against Corona: What we currently know
Status: December 7 2020
MHH infectiologist Professor Dr. Matthias Stoll explains the current status of the corona vaccine.
Among the promising vaccine types are live and dead vaccines, vector vaccines and recently also mRNA vaccines. What are the differences?
Prof. Stoll: The basic principle of any vaccination is that a specific immune response directed against the antigen is specifically induced in the body by molecular structures foreign to the body ("foreign antigens"). After this learning phase of the immune system, the antigen can later be called up quickly and effectively - for example, if the foreign antigen is recognized on an infectious agent and prevents the respective disease from breaking out.
In the past, dead vaccines consisted of completely killed pathogens, hence the name dead vaccine. Nowadays, only partial components (so-called split vaccines or subunit vaccines) or artificial, genetically engineered antigens of specific pathogens are usually used instead. All the variants mentioned are combined as inactivated vaccines in order to make it clear that the pathogen(s) (components) in these vaccines cannot multiply by themselves. Inactivated vaccines stimulate the body's own defense system, especially to produce antibodies.
Live vaccines consist of pathogens that are capable of replication but are attenuated. These do not trigger the disease itself, but can occasionally cause a temporary, harmless "vaccination disease".
Vector vaccines belong to the group of live vaccines and consist of pathogens that are harmless to humans and which carry antigens of the pathogen through targeted genetic modification. The carrier virus - also known as vector virus - modified in this way functions more or less like a Trojan horse, with which the blueprint for an immune response against an infectious disease is offered to the center of the immune defense for replication.
m-RNA vaccines are basically a further development and minimization of the Trojan horse principle of a vector vaccine: the vector virus, which is not necessary for the actual immunization, is dispensed with and instead only a genetically engineered genetic information of pathogen antigen(s) is introduced for vaccination. The vaccinated person's own cells are temporarily stimulated to produce this foreign antigen and present it to the immune system in a particularly advantageous way. This results in a variety of specific immune responses. A further advantage is that the m-RNA is completely degraded after the work is done and that it is not possible for the human cells to convert genetic information from the m-RNA into the genetic DNA code of our own genetic material. This increases the safety of the vaccination concept because the process artificially set in motion by the vaccination cannot take on a life of its own.
How long does it take to become immune after a vaccination?
Prof. Stoll: A specific immune response - the desired consequence of a vaccination - gradually gets going after just a few days, but it takes about two weeks or a little more until it reaches the desired level. Almost all vaccinations developed against COVID-19 disease then take a second step, however, because a booster vaccination must be given at intervals of three weeks to two months so that the vaccination protection is higher on the one hand and lasts much longer on the other. This means that the COVID vaccinations do not develop their full effect until at least four to six weeks after the first dose.
Does every vaccine make you immune in the same way?
Prof. Stoll: Indeed, there are currently about 50 different corona vaccines in clinical trials worldwide. Each vaccine elicits a specific immune response, but the associated effective protection against infection depends on several factors:
- The selection of a suitable vaccine that triggers the immune reactions that are decisive for protection as precisely as possible and stores these specific immune responses in the long-term memory of our immune system.
- The type of vaccine, e.g. as live vaccine, dead vaccine or RNA vaccine Each vaccination principle leads to different variants of the immune defense. Live vaccines and RNA vaccines are particularly well able to induce several variants of the specific immune defense simultaneously, i.e. not only an antibody response but also a cellular immune response.
Not only the vaccine plays a role, but also factors in the person to be vaccinated. Old age, male sex, certain diseases and the use of certain drugs are some of the factors that are associated with a less pronounced immune response. However, we try to design the vaccines in such a way that even under such conditions a sufficient immune response is still produced.
How long does the vaccination effect last?
Prof. Stoll: For COVID-19, we do not yet know because there are no long-term observations. Unfortunately, the immune reactions against SARS-CoV-2 seem to decrease more rapidly than for many other infections. Whether the immune protection of a vaccination also decreases more rapidly to the same extent is still unknown. Therefore, it could be that regular booster vaccinations might be necessary, as is the case with the flu or tetanus vaccination.
Who should be vaccinated?
Prof. Stoll: As many people as possible in order to achieve a worldwide herd immunity, which in the ideal case would cause SARS-CoV-2 to disappear completely from humanity again. However, at first there will be no vaccine available for everyone, nor will it be possible to vaccinate all 80 million Germans in a few days or weeks. For this reason, the National Ethics Council and other specialized institutions have recommended that priority be given to vaccinating those who have a greatly increased risk of contracting COVID-19 - as well as people in the health care system and employees in so-called systemically important professions, such as the police and fire department. Employees* at the MHH are among the first to be vaccinated.
Should high-risk patients with weakened immune systems also be vaccinated?
Prof. Stoll: Yes! Exactly such people are among the people who should be vaccinated first. In individual cases, however, it must be clarified when the most favorable time for vaccination is during the course of the disease or within the framework of an ongoing immunodeficient therapy. In the case of very severe immune deficiencies, the question of whether the vaccination could cause a risk would also have to be clarified with the treating physician.
Should also people who were already infected with the virus be vaccinated?
Prof. Stoll: So far I am not aware that people who already had COVID-19 were excluded from the vaccination. Such a concept would not make sense either, because it is known that the naturally acquired immune response of these so-called convalescents very often decreased rapidly again.
How great is the risk of problematic side effects?
Prof. Stoll: The two m-RNA vaccines from the companies Biontech/Pfizer and Moderna are said to be quite well tolerated - according to the manufacturers' information and also according to statements by independent study observer boards. Main side effects were rather mild - at least not life-threatening - and temporary, such as headaches and/or reactions at the injection site. On the other hand, data on possible long-term side effects are not yet available, as these are accelerated approvals. However, the potentially increased risk due to the lack of long-term data is taken into account by obligatory and comparatively costly observation and documentation of adverse events in all persons vaccinated with the new vaccines.
What percentage of the population must be vaccinated to stop the spread of the virus?
Prof. Stoll: To achieve herd immunity against the SARS-CoV-2 virus, at least 70 to 75 percent of the population must be immune. These percentages are simply calculated from the basic reproduction number (R0) of the virus, which is given by the Robert Koch Institute and in several published meta-analyses* between 3.3 and 3.8. In a recent representative survey conducted by Barmer Krankenkasse at the end of November 2020, the willingness to be vaccinated against COVID-19 for adult Germans was only 53 percent, while for Lower Saxony it was 56 percent. Unfortunately, however, with these low vaccination rates, the hoped-for transfer to a world without lockdown and AHA rules would not be achievable in Germany.
The questions asked: Vanessa Meyer
*(i) Lin YF et al. Frontiers in Medicine. 2020;7:321; (ii) Liu Y et al. Journal of travel medicine. 2020. 53; (iii) Alimohamadi Y, et al. Journal of preventive medicine and public health. 2020;53(3):151-7.
MHH starts COVID-19 therapy study with blood plasma from convalescents
Status: November 17, 2020
There is still no really promising drug against COVID-19. One option is the treatment with blood plasma of people who have already survived this disease - with so-called convalescent plasma. Antibodies against the virus contained in blood serum could support the immune defence of infected persons in their fight against SARS-CoV-2. Now a new clinical study is to clarify how well this passive immunization actually works. Under the direction of Professor Dr. Rainer Blasczyk, Head of the Institute for Transfusion Medicine and Transplant Engineering at Hannover Medical School (MHH), researchers from the MHH, the clinics in Dortmund, Krefeld, Magdeburg and Essen as well as the Siloah Hospital in Hannover are investigating whether the therapeutic transmission of antibodies against SARS-CoV-2 can prevent severe courses of COVID-19 disease. The multi-center study, entitled COMET, starts this Tuesday at the MHH and is funded by the German Federal Ministry of Health (BMG) with approximately 3.34 million Euros.
Preventing severe disease progression
Although convalescent plasma is already being used in clinics against COVID-19 - due to the special situation in times of a pandemic, an exception is provided for in the German Medicines Act. However, there is still no proof of efficacy for this form of therapy. This is now to be provided by clinical studies. Two of these are already underway, but are investigating plasma administration in critically ill patients. In contrast, 340 COVID-19 patients between the ages of 18 and 75 years, who have a rather mild course of disease, are participating in the COMET study: Although they need to be treated in a hospital, they do not yet require ventilation. Passive immunization with the donated pathogen-specific antibodies could thus prevent lighter COVID-19 patients from having to be transferred to the intensive care unit during their hospital stay. "We believe that the earlier we use adoptive immunotherapy, the better," says Professor Blasczyk. The transfusion physician is therefore convinced that prophylactic treatment - for example for non-infected high-risk patients - could even prevent the disease completely.
Donor plasma is being closely examined
The study participants are divided into two groups. One group will receive 250 milliliters of donor plasma on two consecutive days, the other group will not receive plasma as a comparison group. In order to ensure that the plasmas contain sufficient anti-SARS-CoV-2 active antibodies on the one hand and no potentially harmful substances on the other, the donor plasma is first tested in the laboratories at the MHH Institute of Virology and TWINCORE. "Plasma has two advantages: It is safe and is available within a short time", emphasises Professor Blasczyk. The COMET study runs until the end of next year. However, the transfusion physician hopes to be able to present results much earlier.
For plasma donations COVID-19-Genesene can turn to Institut for transfusion medicine and transplant engineering under RKP-Spende@mh-hannover.de.
Information on the COMET study can be found here.
MHH is looking for volunteers aged 60+ for Corona study
Tuberculosis vaccine is intended to strengthen the immune system against the corona virus in older people.
Status: November 05, 2020
A vaccine against tuberculosis could help to achieve a stage victory against the corona virus. The MHH is therefore increasingly looking for people over 60 years of age to be vaccinated with the so-called immune booster VPM 1002. The preparation is intended to strengthen the immune system in its fight against the Sars-CoV-2 pathogen. "VPM 1002 is the genetically improved variant of a vaccine that is decades old and is used in many countries to fight the tuberculosis pathogen," says Professor Dr. Christoph Schindler from the Hannover Medical School (MHH), head of the CRC Core Facility at the Clinical Research Center Hannover. Because the vaccine apparently not only helps against the Tuberculosis bacterium but also improves the immune response in general, it could also strengthen the defense against the corona virus. "In the ideal case, the vaccination reduces the probability of contracting corona virus disease," explains Professor Schindler. Interested persons can contact us at: Telephone (0511)-5350 8333 (recruitment telephone) or by e-mail at: CRC.Studienteilnahme@mh-hannover.de
SARS-CoV-2: How many neutralizing antibodies are needed for protection?
Status: November 05, 2020
Infections with the coronavirus SARS-CoV-2 can progress in very different ways: While some people have no symptoms, others fall seriously ill. An important question that often arises after surviving an infection is the extent to which neutralizing antibodies against the virus have been produced, as only these can protect the body from re-infection.
To detect neutralizing antibodies, infectious viruses, living cells and laboratories with a high safety standard are usually required. Due to the very high requirements of this test, only very limited blood samples from convalescent patients can be tested for the presence of neutralizing antibodies in blood serum. "To change this, we have developed a very simple and rapid procedure that requires only two proteins that are important for the infection process: The spike protein of the virus and the protein ACE2 of the cell. If the binding of the spike protein to ACE2 is suppressed by serum antibodies, these antibodies are also able to prevent the infection of cells with the virus," says Dr. Berislav Bosnjak from the Institute of Immunology at the Hannover Medical School (MHH). He is first author of the study now published in the journal Cellular and Molecular Immunology.
New test can be further developed for the clinic
"With the help of the test developed by us it is now possible to examine a large number of patients over a longer period of time in clinical studies and to determine how long these so important antibodies are present in the blood", emphasizes Professor Dr. Reinhold Foerster, head of the MHH Institute of Immunology and senior author of the study. The new method is still only available for research. However, it could potentially be adapted so that it can be used for routine tests in the future.
With both the previous and the new method, the team was able to show that about ten percent of SARS-CoV-2 infected persons had no protective antibodies in their blood. This primarily affected infected persons who showed only mild symptoms and were only ill for a short time. On the other hand, the patients developed many antibodies that had stronger symptoms and were ill for longer periods of time. "It is still unclear how much neutralizing antibody is needed to protect convalescents from re-infection. But with the test now available, it will be possible to answer this important question more quickly," says Professor Förster.
Other staff members of the MHH Institute of Immunology, the Institute of Virology and the Institute of Transfusion Medicine and Transplant Engineering were involved in the study. Teams of the Clinic for Rheumatology and Immunology as well as the Clinic for Pneumology and the German Primate Center in Göttingen also participated.
The research project "Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods" was funded by the Corona Research Funding Program of Lower Saxony, the Cluster of Excellence RESIST and the Collaborative Research Center SFB 900 of the German Research Foundation.
Keyword: Neutralizing antibodies
Of the antibodies that people have in their blood after successfully surviving an infection with SARS-CoV-2, the neutralizing antibodies are particularly effective. They are a particularly important group of antibodies because they dock to the virus and prevent the virus from entering and multiplying in human cells. Neutralizing antibodies can therefore switch off the virus.
You can find the original paper here.
Corona tests and basics of therapy: MHH researches with
Together against Corona: The Hannover Medical School is involved in eight projects of the National Network of University Medicine.
Status: October 23, 2020
Good research needs good networks, especially in times of global challenges. In the fight against the coronavirus SARS-CoV-2, this is being done in Germany with the "National Network of University Medicine on Covid-19". A network of all German university hospitals is addressing urgent research topics and bundling cross-clinical research activities in 13 projects to tackle the corona pandemic. The Hannover Medical School (MHH) is involved in eight projects. "I am pleased that the MHH is able to contribute its proven research expertise and experience in the treatment of Covid-19 patients and thus contribute to the best possible care for patients throughout Germany," said MHH President Professor Dr. Michael Manns. The Federal Ministry of Education and Research (BMBF) is supporting the research activities in the network with a total of 150 million euros.
The MHH is involved in the following eight network projects of the National Network of University Medicine:
B-FAST - "Nationwide Research Network Applied Surveillance and Testing
Surveillance comprises the observation, analysis, interpretation and reporting of health data. The corona pandemic shows that different testing and surveillance strategies are needed for the entire population, schools and daycare centers, potential risk areas and clinics. B-Fast is developing a platform where such strategies can be tested. To do so, it brings together different analyses and assessments. In this way it supports strategies that not only help in the acute crisis, but can also be transferred to future pandemics.
COVIM - "Determination and use of SARS-CoV-2 immunity
In the project, numerous university hospitals cooperate to combine immunological data from population studies and the investigation of Covid-19 genesis and to generate new scientific knowledge about immunity against SARS-CoV-2. Furthermore, it shall be investigated how the immunity can be transferred to other persons and used for new therapeutic approaches. COVIM closely cooperates with the projects also funded in the network University Medicine, in particular with NAPKON, B-FAST and CEO-sys.
DEFEAT PANDEMIcs - "German Research Network Autopsies in Pandemics
In the project, a Germany-wide autopsy network is being established, in which data, biomaterials and findings are systematically and in a standardized way collected and brought together. This unique networking of most of the pathological, neuropathological and forensic institutes of German university hospitals as well as non-university partners will enable a deeper understanding of the disease and help to develop more effective therapeutic approaches.
EViPan - "Development, testing and implementation of regionally adaptive care structures and processes for evidence-led pandemic management coordinated by university medicine"
A national pandemic management is needed to identify and treat Covid-19 patients even faster and better in the future and to maintain optimal routine care. It also helps to prevent infections and provides an ethical and normative evaluation of care scenarios under pandemic conditions in order to be better prepared for future pandemics. As internationally networked maximum care providers and research institutions, university hospitals are at the center of regional health networks. In the project, they cooperate with the Robert Koch Institute, the public health service and the state governments in order to jointly achieve the goal.
FoDaPl - "National Research Data Platform
In this project, a nationwide uniform, data protection-compliant infrastructure for the storage of Covid-19 research data sets will be created. In this research data platform, for example, laboratory data can be made available to researchers in pseudonymized form using secure and transparent procedures. Thus, the platform will become a central source of information for various research projects dealing with the development of better treatment approaches for Covid-19.
NAPKON - "National Pandemic Cohort Network
The NAPKON project is creating the basis for a better understanding of the course of disease in Covid-19 and for research into possible therapies by bringing together clinical data, biosamples and imaging data in scientific studies. NAPKON is closely linked to the establishment of the National Research Data Platform and cooperates with the COVIM project. The studies thus made possible can, for example, provide information on the long-term consequences of covid-19 disease, even if the patients change their family doctor during treatment, for example, from the clinic to their family doctor.
PallPan - "National Strategy for Palliative Care in Pandemic Times
In this project, recommendations for action and information material are being developed on a scientific basis in order to provide the best possible care for seriously ill and dying people, even in pandemic times, and to take their concerns - and the concerns of their relatives - into account. This is the largest structured association of palliative care in a research project in Germany to date. All areas of outpatient and inpatient hospice and palliative care (general practitioners, specialists, nursing services, palliative services, homes, hospitals, hospices) are considered.
RACOON - "Radiological Cooperative Network on Covid-19 Pandemic
RACOON is the first Germany-wide radiology platform in which almost all university hospitals are involved. Here, radiographs of patients with suspected Covid-19 are brought together and related to the course of the disease. The findings are analyzed using artificial intelligence. This enables a faster and more precise diagnosis of the disease and its progression and provides a basis for decision-making in epidemiological studies, situation assessments and early warning mechanisms.
For further information on the B-FAST project, please contact Professor Dr. Dr. Michael Marschollek by phone (0511) 532-5295 or at email@example.com
For further information on the COVIM project, please contact Professor Dr. Thomas Schulz by phone (0511) 532-6737 or at firstname.lastname@example.org
Further information to the project DEFEAT PANDEMIcs receives you with professor Dr. Danny Jonigk under telephone (0511) 532-9532 or under email@example.com
For further information on the EViPAN project, please contact Professor Dr. Jörg Haier by phone (0511) 532-19307 or at firstname.lastname@example.org
Further information to the project FoDaPl receives you with professor Dr. Dr. Michael Marschollek under telephone (0511) 532-5295 or under email@example.com
Further information to the project NAPKON receives you with professor Dr. Thomas Illig under telephone (0511) 532-7856 or under firstname.lastname@example.org
Further information to the project PallPan receives you with professor Dr. Nils cutter under telephone (0511) 532-2744 or under email@example.com
Further information about the RACOON project can be obtained from Professor Dr. Frank Wacker by phone (0511) 532-3422 or under firstname.lastname@example.org
MHH researchers find possible helpers against COVID-19 infection in the heart
Status: October 2, 2020
Infections with bacteria and viruses are an additional burden on the cardiovascular system. This also applies to the coronavirus SARS-CoV-2, but the virus appears to cause heart damage not only in older people with underlying cardiovascular diseases. Even slightly ill younger patients can show inflammatory changes in the heart muscle or pericardium after surviving COVID-19 infection. This is caused by the angiotensin-converting enzyme 2 (ACE2). This binding site is the gateway for SARS-CoV-2 to enter the lung tissue. Because ACE2 is also found in heart muscle cells, the viruses can also attack the heart and cause massive inflammation there. A research group at the Institute for Molecular and Translational Therapeutic Strategies at Hannover Medical School (MHH) has now discovered a way to block this pathway for the coronavirus. The study under the direction of Institute Director Professor Dr. Dr. Thomas Thum Dr. Christian Bär has been published in the Journal of Molecular and Cellular Cardiology. First authors are Dongchao Lu and Shambhabi Chatterjee, PhD.
Corona viruses attack cells via ACE2 enzyme
ACE2 controls the salt and fluid levels in the body and regulates blood pressure. As one of the major receptors for SARS-CoV-2, ACE2 is also a potential target for COVID-19," said Professor Thum. His research team has been looking for ways to down-regulate the enzyme concentration and, using bioinformatics methods, has discovered a group of microRNAs that control the process. microRNAs are tiny, non-coding RNA snippets that do not implement a genetic blueprint, but can very specifically prevent the construction of individual proteins in the cell.
miR-200c downregulates ACE2 activity
"One candidate in particular, called miR-200c, was able to significantly downregulate ACE2 activity in rat heart muscle cells and in human cardiomyocytes produced from stem cells in the laboratory," said study leader Dr. Baer. In the next step, the promising results from the cell culture experiments must now be tested in living organ simulations. If the study is also successful in a mouse model, the use of miR-200c could be an important strategy in the fight against corona viruses in the future - even if an effective vaccine is available. "The pathogens causing the serious respiratory diseases SARS and MERS are also among the corona viruses that enter cells via ACE2," Professor Thum emphasizes. It is therefore not unlikely that this mechanism can also be used in a future coronavirus pandemic.
The original publication "MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes" is available online here
Virtual visit to the MHH-Kreißsaal
Status: August 25, 2020
MHH goes new ways to inform pregnant women in times of Corona / Every Monday a live broadcast with expert discussions starts at 6.30 pm / Registration by mail
The gynaecological clinic of the Hannover Medical School (MHH) is a very popular address for pregnant women in the Hannover region. "We offer our committed and highly professional care for normal birth up to and including high-risk pregnancy," says clinic director Professor Dr. Peter Hillemanns. While prospective parents were able to visit the maternity clinic before the corona crisis, the gynecological clinic now has to find new ways to reach future mothers and fathers. Even under the clear limitations of the COVID 19 crisis, the gynecological clinic would like to give all expectant parents the opportunity to obtain information about the delivery room at the MHH through direct contact. "Therefore we are now pleased to offer the first web-based information evening for expectant parents in Hanover", Nina Meier, midwife in the delivery room. "We want to show the parents that they are not alone with all their questions.
Ask questions directly to the experts
Every Monday at 6.30 p.m. expectant parents can inform themselves about topics concerning pregnancy and birth at the MHH in a live broadcast. In addition, they have the opportunity to ask questions directly to the MHH experts after the general introduction and to talk to them.
Interested parties can obtain the access data via an informal e-mail to email@example.com. The live broadcast via the Microsoft Teams program begins every Monday at 6:30 pm. Technical requirements are a computer with (integrated) camera, microphone and speakers or headphones. Access is also possible with a tablet or smartphone.
Further information about the MHH Maternity Hospital is also available at www.mhh.de/praenatalmedizin-und-geburtshilfe-im-perinatalzentrum.
MHH researches late effects of corona infection
Status: July 24, 2020
COVID outpatient clinic for officially recovering accompanies concerning / participant inside and participants for study searched.
Recovered, but not healthy: Some people who were ill with COVID-19 still suffer weeks and months after the acute illness from its consequences. The symptoms include tiredness, reduced physical resilience, lack of concentration, breathing problems and loss of taste or smell. "These late effects are not only seen in patients who were severely affected and were treated as inpatients, but also in those with a moderate or mild course of the disease," explains Professor Dr. Marius Hoeper, acting director of the Department of Pneumology at Hannover Medical School (MHH). In his clinic there is the COVID outpatient clinic for convalescence, where patients are accompanied after their illness. To find out more about the late effects, Professor Hoeper and his team are conducting the study "IRMI 19" (ImmunpRofile iM long-term course after COVID-19).
The COVID outpatient clinic for convalescents is available since mid-May. "There are patients who still do not feel well three or four months after the illness", explains Dr. Isabell Pink, head of the outpatient clinic. For some of them it is difficult to pursue their profession due to the complaints, even if it is "only" an office job. Many complained of shortness of breath under stress and a tightness in the chest. Among them were also patients between 21 and 50 years of age who had been completely healthy before infection with the SARS-CoV-2 virus. "Their situation is improving only very slowly," says the pneumologist. Medically, she cannot offer the patients much. "We can only advise them to listen to their body, to shift down a gear altogether and, if necessary, to apply for outpatient rehabilitation".
Half a year under observation
Nevertheless, those affected appreciate the care in the outpatient clinic. They feel safer if they are accompanied by a doctor and their condition is observed over a longer period of time. In the outpatient clinic, the experts follow the course of the disease for at least half a year. Patients are examined three times: six to eight weeks, three months and six months after acute SARS-CoV-2 infection. These include a lung function test, analysis of blood, urine and saliva, a physical examination and a stress test, and imaging diagnostics if necessary. There is close contact with other disciplines, which are consulted as required.
Little is known about the long-term consequences of coronavirus infection. However, previous research and clinical observations have shown that SARS-CoV-2 can infect practically any organ and cause damage there. "We assume that COVID-19 has a lasting effect on the immune system," explains Professor Hoeper. Through the "IRMI 19" study, he and his team hope to gain new insights into the late effects of the virus infection. "We assume that there are correlations between the observed immune phenomena and the persistent symptoms, which we would like to understand better, of course also in the hope to be able to treat them in the future". Immunoprofiles should provide information about this in the long-term course.
About 100 affected persons, who originally had only a mild COVID-19 disease but still suffer from late effects, will participate in the study. The study may also include patients who were not treated at the MHH. They can register at the COVID outpatient clinic for convalescence.
Interested persons can reach the COVID outpatient clinic for convalescents under telephone (0511) 532-5030, fax (0511) 532-18538 or e-mail: firstname.lastname@example.org.
Further information receives you with Dr. Isabell Pink, hospital for pneumology, under telephone (0511) 532-9314 or email@example.com.
T lymphocytes play an important role in the course of COVID-19
MHH research team publishes first European study of this kind in the Lancet journal "EBioMedicine
Status: 08 July 2020
Infections with the coronavirus SARS-CoV-2 can take very different courses - some people remain completely without symptoms or show a mild course of the disease. Others have to be treated in hospital. But even here there are differences between patients who need to be ventilated in intensive care units and those who are less likely to get COVID-19. A research team at the Hannover Medical School (MHH) has found out how these two groups of patients treated in hospitals differ immunologically. Led by the Institute of Immunology and the Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, the researchers studied the blood of COVID-19 patients. They found out that a certain composition of lymphocytes, which are responsible for targeted immune defence, plays an important role in the course of the disease. The research was the first European study of its kind to be published in the Lancet journal "EBioMedicine". The first author is Dr. Ivan Odak.
Number of T-lymphocytes decreases in seriously ill COVID-19 patients
"We were aware that patients with severe COVID-19 disease generally have fewer lymphocytes in their blood," says Dr. Christian Schultze-Florey, who is the co-principal investigator of the study with Professor Dr. Christian Könecke. "However, we did not know which specific subgroups and to what extent they were actually affected. Lymphocytes belong to the white blood cells and, like all blood cells, are formed in the bone marrow. They then have to go through a maturation process in the body before they can recognise and fight foreign cells such as bacteria or viruses as T or B lymphocytes. In severe cases of COVID-19 - such as patients requiring respiration - all lymphocyte subtypes were found to be reduced compared to healthy controls. This was significantly less pronounced in mild COVID-19 patients.
"Another groundbreaking finding was that COVID-19 patients with mild disease had more effector T-cells already at hospital admission than patients with a severe course," Professor Könecke explains. Effector T-cells are particularly activated T-cells that either destroy diseased cells directly or alarm the immune system with messenger substances and thus attract additional immune cells. The researchers also found differences in the course of COVID-19 disease. If patients recover from infection with SARS-CoV-2 and their health improves, the number of effector cells in the blood also increases significantly. Memory cells, which are a special form of T-cells that recognise pathogens during a renewed infection and can therefore fight them more quickly, can also be detected more strongly again during recovery. If the disease does not improve, however, there is no such increase.
More targeted diagnosis and more effective treatment possible
"The T-cell immune response seems to play a crucial role in COVID-19," says Professor Förster, head of the Institute of Immunology. The general decrease in lymphocyte subtypes and effector T cells could therefore serve as a biomarker to assess the severity of the disease at an early stage by measuring the immune status. "This is important because some patients initially appear clinically stable when they are admitted to hospital, but a severe COVID-19 course occurs a little later," emphasises study leader Schultze-Florey. These patients could be treated faster and more effectively through a targeted diagnosis. The course of treatment could also possibly be predicted with the help of T-cell markers. This would make it possible to check during treatment whether patients respond and their state of health is likely to improve.
The research project "Reappearance of Effector T Cells Is Associated With Recovery from COVID-19" was funded by the Corona Research Funding Programme of the state of Lower Saxony, the "RESIST" cluster of excellence and the Collaborative Research Centre (SFB) 900 of the German Research Foundation.
For further information, please contact Dr. Christian Schultze-Florey at phone (0511) 532-9725 or firstname.lastname@example.org.
The original publication is available online at https://authors.elsevier.com/sd/article/S2352396420302607.