General information on the coronavirus pandemic

SARS-CoV-2, the in December 2019 newly identified coronavirus strain, has already infected 13 378 853 people worldwide (confirmed cases as of 17 July 2020, WHO). The corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 infections imposes a major threat for the world’s health care systems and is leading to thousands of deaths. As of July 17, already 580 045 confirmed SARS-CoV-2 infected patients died (WHO). The virus binds to and invades the alveolar lung cells through the angiotensin converting enzyme 2 (ACE2). Most common symptoms are fever and dry cough. Most patients have mild cold symptoms, the rather severe cases suffer from dyspnea, low blood oxygen saturation and lung infiltrates. The critical patients (around 5%) experience respiratory failure, and/or multiple organ dysfunction or failure. ACE2 is not only expressed on lung cells but also in the heart and vascular endothelium and COVID-19 is linked to increased morbidity and mortality from cardiovascular disease.

Prof. Werner Seeger on the COVID-19 pandemic

Current publications on COVID-19 from CPI members

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

Valentina O. Puntmann, MD, PhD1; M. Ludovica Carerj, MD1,2; Imke Wieters, MD3; Masia Fahim3; Christophe Arendt, MD1,4; Jedrzej Hoffmann, MD1,5; Anastasia Shchendrygina, MD, PhD1,6; Felicitas Escher, MD7; Mariuca Vasa-Nicotera, MD5; Andreas M. Zeiher, MD5; Maria Vehreschild, MD3; Eike Nagel, MD1

Question  What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?

Findings  In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.

Meaning  These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916

Coronavirus Disease 2019 (COVID-19) and its implications for cardiovascular care: expert document from the German Cardiac Society and the World Heart Federation.

Coronavirus Disease 2019 (COVID-19) and its implications for cardiovascular care: expert document from the German Cardiac Society and the World Heart Federation.
Böhm M, Frey N, Giannitsis E, Sliwa K, Zeiher AM.
Clin Res Cardiol. 2020 May 27. doi: 10.1007/s00392-020-01656-3. [Epub ahead of print] Review.

Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. EHJ

ACE2 is a protein on the surface of cells and serves as the entry gate for the SARS-CoV-2 coronavirus. A Frankfurt research group was able to show that ACE2 is significantly increased in tissue samples from patients with cardiovascular diseases.

COVID-19 disease causes severe lung damage with thousands of deaths. It is already known that the SARS-CoV-2 virus attacks lung cells that present a specific protein on their surface, the so-called ACE2 receptor. So far, mainly the effects of COVID-19 on lung health have been reported. However, patients with cardiovascular diseases are affected by a considerably more severe course of the disease. You have a multiple increase in mortality from COVID-19 disease. There is currently a lot of discussion about which cells contain ACE2 and whether so-called angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARB) are used to enhance the presentation of the SARS-CoV-2 receptor ACE2 in the lungs and lead heart cells. Both are drugs that are often used to treat cardiovascular diseases.

An interdisciplinary cardiac research team at the University Hospital Frankfurt led by Prof. Stefanie Dimmeler, director of the Institute for Cardiovascular Regeneration, Prof. Andreas Zeiher, director of cardiology, and Prof. Thomas Walther, director of the Cardiac surgery, showed in a publication in the European Heart Journal the differences of the ACE2 presentation on tissue samples from patients with cardiovascular diseases. The researchers discovered that ACE2, especially in cardiac muscle cells and in the vascular cells of the heart of patients with heart disease, was significantly increased compared to healthy control groups. Interestingly, the investigations were also able to demonstrate for the first time that cardiac cells from patients treated with ACE inhibitors had a significantly higher ACE2 presentation.

These data suggest that it is not only important to monitor SARS-CoV-2 infected for cardiovascular complications, but in particular to further investigate the influence of ACE2 inhibitors and ARB blockers on the course of disease of COVID-19.

original publication: Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Luka Nicin et.al. European Heart Journal, ehaa311, https://doi.org/10.1093/eurheartj/ehaa311

podcast:https://www.escardio.org/The-ESC/What-we-do/news/ESC-Cardio-Talk

Quelle: Pressemitteilung Universitätsklinikum Frankfurt

SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes
Denisa Bojkova, Julian Wagner, Mariana Shumliakivska, Galip Aslan, Umber Saleem, Arne Hansen, Guillermo Luxan, Stefan Guenther, Minh Duc Pham, Jaya Krishnan, Patrick Harter, Utz Ermel, Achilleas S Frangakis, Andreas Zeiher, Hendrik Milting, Jindrich Cinatl Jr., Andreas Dendorfer, Thomas Eschenhagen, Sandra Ciesek, Stefanie Dimmeler

Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.

Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.

Bojkova D, Klann K, Koch B, Widera M, Krause D, Ciesek S, Cinatl J, Münch C.

Nature. 2020 May 14. doi: 10.1038/s41586-020-2332-7.

Single-Cell Transcriptomics Data Survey Reveals SARS-CoV-2 Entry Factors Highly Expressed in Nasal Epithelial Cells Together with Innate Immune Genes

In this study, we have investigated which cells in the body can be infected by the covid-19 virus (SARS-CoV-2). We use data from a large-scale international project that aims to map all cells in the body according to their gene expression profiles (Human Cell Atlas Project).

It is known from previous studies that the covid-19 virus can only infect cells that express two genes necessary for viral entry into human cells (ACE2 and TMPRSS). By examining their expression levels in thousands of cells from human tissues, we discovered that ACE2, along with TMPRSS, is expressed in epithelial cells of the respiratory system, cornea and intestine which may explain the extensive spread of the covid-19 virus. These genes are expressed primarily in the nasal cells along with other genes that are part of our innate immune system. This highlights the potential role of nasal cells in early infection and in counteracting infection. The expression of ACE2 together with TMPRSS2 in other barrier tissues points to the need to investigate alternative transmission pathways. For example, the expression of the genes in the esophagus and colon could explain why the virus has been found in the stools of COVID-19 patients, indicating a potential fecal-oral transmission. Expression of the genes in superficial epithelial cells in the eye may explain symptoms in the eye that can be observed in a small proportion of COVID-19 patients. These discoveries have implications for our strategies to protect us and to treat infected individuals. For example, given the likely role of the nasal cells, drugs administered intranasally may be very effective in limiting both infection and spread.

original publication: Single-Cell Transcriptomics Data Survey Reveals SARS-CoV-2 Entry Factors Highly Expressed in Nasal Epithelial Cells Together with Innate Immune Genes. Waradon Sungnak et al., Nat Med (2020). https://doi.org/10.1038/s41591-020-0868-6

Quelle: Summary by Christos Samakovlis

 

The CPI is working with great effort on understanding COVID-19 pathology and the development of potential treatment options.

We are currently investigating the following major questions:

How can lung injury induced by SARS-CoV-2 be prevented?

There are immense activities world-wide to identify novel therapeutic options for treating COVID-19. Based on previous studies of CPI researchers demonstrating that inhaled GM-CSF prevents lung failure of acute pneumonia (Cakarova et al, AJRCCM, 2009; Unkel et al, JCI, 2012), and a multicenter phase II trial is currently testing this therapeutic strategy in pneumonia-realted ARDS including COVID patients. This approach might be also suitable to prevent detrimental development of COVID-19-ARDS from early stages of pneumonia. Depending on the availability of substance, a clinical trial is planned.

In addition, cell therapies showing that immunosuppressive mesenchymal stromal cells protect bronchopulmonary stem cells destruction caused by virus infection were shown to prevent detrimental courses of the disease (Salzig et al, EMBOJ, 2019). In collaboration with the LOEWE Center for Cell- and Gene Therapy, highly efficient, off the shelf available immune suppressive MSCs were developed, which might be usable also as therapeutics for COVID-19.

Does SARS-CoV-2 directly affect the vasculature and the heart?

The putative receptor for SARS-CoV-2 ACE2 is not only expressed on lung cells but also in the heart and vascular endothelium (Wevers and Hoek, Futur Med, 2010). Moreover, patients with underlying cardiovascular disease represent a significant proportion of patients, who may suffer from severe courses after COVID-19 infections (Zhou et al, The Lancet,2020; Wang et al., JAMA, 2020; Zheng, Nat Rev. Cardiol., 2020). Therefore, the CPI is addressing the impact of COVID-19 on the cardiovascular system. First data suggest that particularly pericytes and cardiomyocyte showed highest expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Therefore, CPI researchers now test whether SARS-CoV-2 can directly affect cells of the cardiovascular system by assessing the effect of SARS-CoV-2 isolates on primary human cells in collaboration with Prof. Ciesek (Frankfurt).

Could ACE-inhibitor treatment be detrimental in COVID-19 patients?

First studies show that ACE-inhibitor treatment, which is often used to treat patients with cardiovascular diseases, augments the expression of the SARS-CoV-2 receptor ACE2 in lung cells. This is supposed to be mediated by an effect on angiotensin II, which is known to reduce ACE2 expression. Thus, ACE inhibition decreases angiotensin II, leading to an indirect up-regulation of ACE2 (Wevers and Hoek, Futur Med, 2010). To test whether this indeed is relevant in the context of COVID-19, CPI researchers are currently determining the regulation of ACE2 in patients, which were treated with ACE2 inhibitors. In addition, ex vivo lung explants (precision-cut lung slices, PCLS) are treated with angiotensin-II-receptor blockers or ACE-inhibitors to study effects on lung cells. Moreover, the CPI teamed up with the European registry LEOSS (https://leoss.net/about/) to clarify, whether there is any hint for detrimental courses of ACE inhibitor treated COVID-19 patients.

How does the host cell respond to SARS-CoV-2 infection?

So far, there is little knowledge regarding the cellular pathways activated upon SARS-CoV-2 infection. However, these cellular processes are key to understanding how the virus replicates in cells and how this could be pharmacologically perturbed. CPI researcher Christian Münch, together with the Cinatl laboratory (Virology, University Hospital Frankfurt), addressed this question. They developed a human epithelial cell infection system with viral isolate from a COVID-19 patient and studied the protein and translation changes after infection over time. They discovered several key pathways and showed that inhibition of these pathways prevents viral replication in cells (preprint: https://www.researchsquare.com/article/rs-17218/v1). This opens up several new avenues of therapeutic strategies to target COVID-19.

CPI joined “Frankfurt Debate”

The “Frankfurt interdisciplinary debate” is an attempt at dialogue between representatives of different scientific disciplines on current issues – currently (and certainly for a while) in the context of the corona crisis.

To visit the “Frankfurt Debate” website click here…

CPI sites joined LEOSS

The Lean European Open Survey on SARS-CoV-2 Infected Patients studies SARD-CoV-2 collectively.

Why: To gather information on the best possible clinical management of patients as well as prediction and prevention of severe outcomes

How: LEOSS establishes a quick and simple register that allows anonymous documentation of patients. This data can be used to identify independent predictors of outcome in patients with diagnosed infection by SARS-CoV-2.

For more information visit: 

How does COVID-19 crisis affect CPI members

Prof. Dr. Dr. Thomas Braun, coordinator CPI

How does the COVID-19 pandemia affect basic science research?

COVID-19 has turned our research upside down. We try to cope as best as we can with the situation but regular routines have been disrupted and most colleagues work in home office. On the other hand, this unusual and challenging situation offers new opportunities, allowing us to finish manuscripts and think about innovative projects and concepts. Despite the current limitations, we have intensified our research on lung regeneration. which seems more important than ever to cope with the devastating effects of viral infections of the lung.

Dr. Guillermo Luxan, postdoc

How does COVID-19 affects science and society in Spain as compared to Germany?

My family and friends live in Madrid that has become into one of the main centers of COVID-19 in Spain, and in Europe. This pandemic affects everything in Spain, from human relationships to science, of course, as all the efforts are devoted to stop the spread of the virus. My parents, my grandmother, my friends and colleagues have not abandoned their flats in the last two weeks, and now the government has ordered two more weeks of confinement with even more strict restrictions. The country has been brought to a stop and this also means its science. Research Institutes are closed, and yes, data can be analyzed from home and papers and thesis can be written from home but the laboratories are not producing any new data and at some point, the whole research effort in Spain will also come to a complete stop.

The differences with Germany are enormous. Although our lives have been affected by the spread of the disease, it can’t be compared at any level with Spain, or Italy. Here, live goes on. I see, in one hand, responsibility regarding social distancing. We, in the lab, have reduced the our presence to a minimum. We take shifts in the labs to reduce amount of people at the same time in one room and all our meetings are gone online. But on the other hand, it is not uncommon to see people gathering in the river and in the parks in the evening.

I really hope that all the measures and preparations that Germany has undergone expecting this ticking bomb to explode are enough and that we don’t need to stop our lives like my family and friends in Madrid. I also hope, that once this is over, Germany and the other EU countries help Spain, and Italy, to recover from the economic crisis that will come after the clinical crisis because there is going to be a lot of help needed.

Dr. Nuno Guimarães Camboa, junior research group leader

How does it feel to start living in a shut down country and how does the situation affect your scientific work?

Start living in a shut down country: We moved the entire family (including two 8-month-old babies) just before the crisis exploded in Italy. The day we left Milan there were some people wearing masks on the street, but life was proceeding normally, with all essential and non-essential businesses functioning as usual. Immediately after our arrival in Frankfurt, the number of cases in northern Italy started escalating dramatically and the government implemented strict lockdown measures. Since we closely followed the situation in Italy and the first cases were also being reported in Germany, we placed our family in social isolation even before the German Federal government imposed current restrictions. This scenario is certainly not the one we were hoping for when moving to Frankfurt. We were looking forward to introducing our twin daughters to our friends and taking advantage of the beautiful sunny days to explore the city and enjoy strolls by the Main on weekends. Nonetheless, this is still a much better scenario than the one we would be facing if the family would still be in Milan where the lockdown is much more strict: you are not authorized to leave your home except for essential needs (and whenever you go out you need to carry a declaration stating the reason why you are outside your place) and even simple tasks such as going to the grocery store become complex, with most supermarkets having waiting lines of 30 mins to one hour just to get in.
Impact of COVID-19 on scientific work: the social distancing measures necessary to stop spreading the virus significantly affect our capacity to perform experiments. Our institute did not shut down, but has implemented strict rules allowing a single person per room at all times, which tremendously reduces the number of people who can be at work at any given moment. Currently, we are mostly doing maintenance work and concluding experiments we had previously initiated. Lab members are encouraged to work from home as much as possible (specially those who would need to take public transportation to get to work) and we are taking this forced break to carefully organize data generated in recent months and plan future experiments. This situation will certainly have an impact on the timeline of our projects. Similarly to other professional areas, the degree of this impact will ultimately depend on how long the need for social isolation extends.

CPI PI Prof. Susanne Herold about the current Corona Virus Outbreak:

Prof. Susanne Herold cited in the New York Times “A German Exception? Why is the Country´s Coronavirus Death Rate is Low”, 04.04.2020

Prof. Susanne Herold in hartaberfair-extra: Das Virus befällt die Wirtschaft: Wieviel bleibt von unserem Wohlstand?, 30.03.2020

Prof. Susanne Herold with the Minister of Health Jens Spahn and RKI-President Prof. Lothar Wieler in a press conference, 26.03.2020

Prof. Susanne Herold in an Interview in Steingarts Morgenbriefing, 23.03.2020

Prof. Susanne Herold in maischberger. die Woche, 18.03.2020

Prof. Susanne Herold in the BMBF Press Conference “Corona-Krise: „Achtsamkeit ja, Alarmismus nein“,  11.03.2020

Prof. Susanne Herold in an interview “Gießener Allgemeine – Kampf dem Lungenversagen“, 09.03.2020

BMBF-Interview with Prof. Susanne Herold “Welche Therapien gegen das Virus gibt es?”, 09.03.2020

Prof. Susanne Herold in Anne Will ” Quarantäne, Hamsterkäufe, abgesagte Veranstaltungen – wie berechtigt ist die Angst vor dem Coronavirus?”, 08.03.2020

Prof. Susanne Herold in an interview at h+ live, 25.02.2020

Prof. Susanne Herold in an interview with Garbor Steingart about SARS-CoV-2, 29.01.2020

Prof. Susanne Herold gave an interview for the Abendzeitung ,30.01.2020

Prof. Susanne Herold in the ZDF special – Kampf gegen das Coronavirus,  05.02.2020.