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Scientists discuss corona studies live on Clubhouse

Mar 9, 2021 // Every week the scientists Geraldine Nouailles, Emanuel Wyler and Benedikt Beckmann together with Ralf Rottmann read and discuss corona studies live on the social media app Clubhouse

During the current pandemic of the new coronavirus, the whole world is watching scientists researching this new virus. In the early days, new discoveries were made almost daily and society became familiar with terms such as "transmission", "polymerase chain reaction" and "mutations".

The need for information and knowledge about the novel coronavirus is still huge but even scientists have difficulties to keep up with new findings and putting them into context. To meet the demand of scientists and non-scientists to understand current public discussions, IRI Life Sciences offers a new weekly science format within the brand-new social app called Clubhouse.

With "Betreutes Lesen auf Clubhouse (Clubhouse Reading Circle)" a group of scientists involved in studying the coronavirus SARS-CoV-2 at IRI Life Sciences (Benedikt Beckmann, group leader at Humboldt-Universität zu Berlin and Emanuel Wyler, senior postdoc in the group of IRI Life Sciences' spokesperson Markus Landthaler from Max Delbrück Center for Molecular Medicine) and Geraldine Nouailles from Charité – Universitätsmedizin Berlin discuss current studies and provide background information. The researchers also give insights into their own research and experiences with the new coronavirus and answer questions from the participants.

Upcoming event

With Geraldine Nouailles, Benedikt Beckmann, Emanuel Wyler and Ralf Rottmann
Read here or check Twitter when the next Clubhouse session will take place.

Past events

Missed a session? Here´s what the scientists discussed

Sources and reading material:

SARS-CoV-2_Wuhan-Hu-1 is the name of the standard coronavirus that very likely triggered the current pandemic. But where does the standard coronavirus come from? In a new study, researchers in China and Australia compared the virus strains of bats with the standard coronavirus.

The results of the study suggest that certain bat viruses do have certain similarities to SARS-CoV-2_Wuhan-Hu-1 that could lead to human cells being infected. However, the doubts about the origin of SARS-CoV-2 are not dispelled by this study. Bat viruses have so many recombination possibilities that the evolutionary origins of the standard coronavirus are elusive.

Sources and reading material

In early 2021, acute supply deficits prevented the vaccination progress in the population. As a result, some governments decided to extend the time intervals between two vaccination doses in order to provide as many people as possible with basic protection against COVID-19 as quickly as possible through a first standard dose.

Researchers in the UK investigated which time interval between the two vaccination doses with the mRNA vaccine from BioNTech/Pfizer works better in the more vulnerable group of older people. They looked at 172 persons over the age of 80 who received two doses of the Pfizer/BioNTech BNT162b2 vaccine. For 99 participants, the two doses were given 3 weeks apart. The remaining 73 participants received both doses within 11-12 weeks.

They found that both vaccination schedules elicited strong antibody responses. However, peak levels were 3.5-fold higher in the prolonged interval regimen at the end.

Sources and reading material

How the innate immune system reacts to SARS-CoV-2 was topic of the today´s clubhouse session. The scientists talked about how our immune system actually reacts to the coronavirus. Long before B and T cells become active, this first line of defense plays an important role; also on the course of the disease.

Sources and reading material

The emergence of SARS-CoV-2 variants have raised the question to what extent the mutations impact immunity induced by either SARS-CoV-2 infection or vaccination. A study (published as preprint) is revealing good news: T-helper cells and T-killer cells in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are responding very well to SARS-CoV-2 mutants so far. That means the highly prevalent mutations B.1.1.7 (UK), B.1.351 (South Africa), P.1. (Brazil) and CAL.20C (California) do not "escape" this part of our immune system so easily.

Sources and reading material

Infection with an endemic corona coldvirus appears to be slightly protective against re-infection with SARS-CoV-2. This is shown in a study published as PrePrint, in which researchers compared T-helper cells (CD4+ cells) from SARS-CoV-2 infected persons with those from non-infected persons. CD4+ cells are part of the control of the immune response.

The CD4+ T cells of study participants already infected with a more innocuous corona coldvirus were apparently found to be protective against the spike protein of SARS-CoV-2. This is strong evidence of a cross-reaction. Unfortunately, this is not relevant enough to prevent SARS-CoV-2 from entering human cells.

The positive message of the study is that both SARS-CoV-2 infection and vaccination stimulate the T-cells very strongly. Therefore the T cell immune response along with B memory cells (see discussed study of 11 March) builds a strong protection against severe courses of disease in case of a renewed infection with SARS-CoV-2.

Sources and reading material

To date, there are no therapeutic targets known to effectively combat COVID-19. Yet a recently published study with data derived from the UK has provoked interest of worldwide media. According to the study, the asthma spray with the active ingredient budesonide proved to be extremely effective in the fight against severe progression and clinical deterioration due to SARS-CoV-2 infections.

In today's clubhouse session, the scientists Geraldine, Benedikt and Emanuel agreed that although there are some good reasons for the use of budesonide (it is cheap, easily available, hardly any contraindications in patients) against COVID-19, the data situation due to e.g. open label processing, small patient sample and self-observation of symptoms, is still much too thin for a clear recommendation of the drug and urgently needs to be specified in further e.g. blinded (not open label) studies.

Sources and reading material

Fear of SARS-CoV-2 mutations is growing. According to current research, the virus variants known so far do not completely neutralise the immune protection provided by existing vaccinations, but they can weaken their effect. This can change, however, if the virus forms new characteristics through ever new mutations in order to evade community protective immunity.

Corresponding to this topic, in a recently published study virologists analyzed the mutation rates of two seasonal human coronaviruses (HCoV) and compared them with a subtype of the human influenza A virus (IAV), which is known to rapidly generate new variants. In contrast to coronaviruses, influenza viruses have a fragmented RNA-genome that supports a high mutation rate and therefore much more subtypes are identified.

To no surprise, the scientists observed a higher mutation rate in IAV than in the compared seasonal coronaviruses. But the reported mutation rate of the current SARS-CoV-2 virus is also higher than that of the analyzed endemic seasonal coronaviruses, but that is due to the high infection rate during the pandemic. However, the scientists assume a plausible post-pandemic scenario would be that the evolution of SARS-CoV-2 will be similar to those of endemic HCoV once sufficient community immune responses against SARS-CoV-2 have been built and infection rates are low.

Sources and reading material

The SARS-CoV-2 mutant B.1.1.7 was first detected in the UK in September 2020 and has since spread to various countries around the globe. It also determines the infection process in Germany. The fact that B.1.1.7 is more contagious than the original coronavirus is shown by its rapid spread. But does mutant also bears a higher risk for a deadly course of infection than the original SARS-CoV-2? An observational study with patient data from UK provides first detailed information.

In the study published March 15, 2021 in Nature, scientists analysed a dataset linking 2,245,263 positive SARS-CoV-2 tests and 17,452 COVID-19 deaths in England from September 1, 2020 to February 21, 2021. Test results confirmed that nearly 674,000 people were infected with B.1.1.7.

The researchers observed a 61% higher hazard of death of a person infected with B.1.1.7 of either sex compared to the classical coronavirus, across all age groups. However, as observed before, significantly more older persons (from 70 and especially from 85) died compared to the group of younger persons after infection with either SARS-CoV-2 variant.

In conclusion, the study proves an individual higher infection fatality ratio for the B.1.1.7 variant compared to the non-mutated virus variant across all ages.

Sources and reading material

The AstraZeneca vaccine is on everyone's lips but not in everyone's arms. Vaccination was stopped in many countries due to reports of thrombosis after vaccination with the Oxford-AstraZeneca vaccine. The three scientists Geraldine, Emanuel and Benedikt looked at the evidence base in current studies. They started with a highly regarded study on the efficacy of the Oxford-AstraZeneca vaccine, also known as ChAdOx1 nCoV-19 or AZD1222, but also took into consideration two further studies that included BionTech-Pfizer´s vaccine BNT162b2 mRNA.

A study published February 19, 2021 in Lancet provides analyses of Oxford-AstraZeneca`s vaccine and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming (= first) and booster (= second) doses. In addition, it shows the immunogenicity and protection after the first dose, before a booster dose has been injected. The study encompasses four trials with data from clinical trials in the UK, Brasil and South Africa with more than 24.000 participants. Three groups of individuals (18-55 years, 56-69 years, ≥70 years) were randomly assigned 1:1 to receive two standard doses of Oxford-AstraZeneca or a control vaccine or saline placebo.

During the study period between April 23 and December 6, 2020, specific antibodies were measured that recognize the spike protein of SARS-CoV-2. In parallel, nucleo-capsid antibodies (these are not formed during vaccination, but only when one has experienced a real infection with the coronavirus SARS-CoV-2) were measured. Therefore, it is very well distinguishable whether a "natural" SARS-CoV-2 infection was present or whether it was a "natural" immune response against vaccination.

The findings of the Lancet study reveal that protection against severe COVID-19 courses already after the priming dose is 70 % and is efficacious in the first 90 days. Thus, UK's strategy vaccinating as many people as possible with the first dose as quickly as possible and delivering the booster dose three months later, seems to work towards a faster population immunity.

Two further studies come to very similar results and demonstrate that the vaccines from Oxford-AstraZeneca as well as BionTech-Pfizer are already highly effective after the first vaccination. A study from Scotland analysed BionTech-Pfizer´s BNT162b2 mRNA and Oxford-AstraZeneca´s ChAdOx1 vaccines with a few hundred participants (18-64 years, 65-79 years, ≥80 years) and confirmed that already a single dose resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland. The so-called SIREN study elicited the effectiveness of BionTech-Pfizer´s BNT162b2 mRNA against SARS-CoV-2 infection and protection against COVID-19 related diseases in healthcare workers in England. This study also provided evidence of a high level of effectiveness of the BNT162b2 vaccine in working age adults even against the circulating B1.1.7 variant.

In summary, the three scientists confirmed the relatively high efficacy of the Oxford-AstraZeneca vaccine on the basis of current studies - even after the first standard dose. According to these three studies, the risk of a severe COVID-19 course in vaccinated patients is considerably reduced after the first dose. As reported in the Lancet study, the amount of protective antibodies in vaccinated persons is even highest when there is a period of 12 weeks between the first and second dose.

More information

Sources and reading material

In this session scientists Geraldine, Benedikt and Emanuel deciphered a study that presents a longitudinal deep profiling of the anti-SARS-CoV-2 memory B cells (MBC) response in two parallel cohorts of patients with severe and mild COVID-19. In the context of the ongoing pandemic caused by the novel coronavirus SARS-CoV-2 it is important to understand the mechanisms underlying the establishment of protective immune memory in recovering individuals.

During an infection, the immune system produces special antibodies against the virus. Responsible for this are so-called B cells. In the case of SARS-CoV-2, antibodies can be measured around 1-3 weeks after infection, but the level of antibodies diminishes after a few months. To be able to react fast in the case of a repeated infection with the same virus, our immune system has a “memory system”.

In some cases, this memory system works towards a sterile immunity, i.e. no reinfection occurs, like for the rubeola virus. For other viruses like the common seasonal coldviruses there is only a partial immunity that protects for severe courses and / or only lasts for a certain time period. One part of this memory system is a special form of B cells, the memory B cells (MBC). In case of a reinfection, MBCs are activated and differentiate to antibody-producing B cells to attack the virus.

For the new coronavirus SARS-CoV-2 an urgent question is how long-lasting is the immunity after an infection since over the past year there have been repeated reports of individuals who were tested positive twice. In this Cell paper, patients with severe COVID-19 were compared with those with a mild course of illness. The authors showed that the antibody titer against SARS-CoV-2 in severe and mild cases were comparable, for severe cases of infection the amount of antibody was in average a bit higher.

Furthermore, they showed that in both patient cohorts specific SARS-CoV-2 memory B cells to recognise the spike protein were produced, again with a higher percentage in average in patients with a severe course of infection. But nevertheless, all measured titer in both cohorts support a solid memory B cell production to provide a long-term protection.

In addition to the above summarized findings, the authors report that they observed that not only the SARS-CoV-2 specific B cells were in the first line of defense, but pre-existing highly mutated MBCs specific to spike proteins of other related seasonal betacoronaviruses were also mobilized. This supports the idea that infections with cold coronaviruses might confer mild protection against SARS-CoV-2.

Overall, the study shows that a lasting and effective immunity develops after a SARS-CoV-2 infection, independently of a severe or mild course of infection. However, this study only included a rather small number of patients and those findings need to be verified in larger patient cohorts.

Sources and reading material

Around 150 Clubhouse members listened to the researchers' discussion of a study shedding light on one of the first identified adaptions of the new SARS-Cov-2 to its new human host. Already early during the spread of the new coronavirus SARS-CoV-2 (around February 2020) it developed a mutation which replaces Aspartic acid (D) with Glycine (G) in the spike glycoprotein - the part of the virus crucial for virus entry. This so called S-614G variant (in contrast to the S614-D of the the original virus variant first identified in Wuhan, China) is now common to all current variants, also within the so-called VoC (variants of concern) like B.1.1.7 and B.1.351.

The discussed study used a generated isogenic SARS-CoV-2 variant and demonstrated that the S-614G variant has enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2) in cell culture and increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model compared to the original S-614D variant. Furthermore, the study shows markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection of the S-614G variant compared to the original wild type.

Collectively, the data shows that this already early upcoming exchange of one amino acid within the spike glycoprotein provides a real competitive advantage, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

Clubhouse-App: What is it? How can I use the app?

Clubhouse is an audio-only app, which means you can listen to conversations like a live podcast or actively participate in discussions. No comments, no likes, no camera turned on, no recording. The app is available for iOS and for Android. If you want to be part of it, you need an invitation! To receive an invitation to Clubhouse, you have to be invited to the Clubhouse app by an already active user.

More information

Beckmann Lab: Betreutes Lesen auf Clubhouse (in German)
Max Delbrück Center for Molecular Medicine: Diskussion von Corona-Studien auf Clubhouse (in German)
Website of Emanuel Wyler (in German)
Website of Ralf Rottmann (in German)