Language of Study: German

Subject Major: Biomedical Science

Country of Study: Germany

Title of Work: SARS-CoV-2: How the Pathophysiology of the Virus Influences the Scope of Vaccine Methods from a German Scientific and Cultural Perspective

Abstract: Arguably one of the most important problems in public health are viruses, as they can cause potentially widespread crises. SARS-CoV-2 is the cause of the current pandemic and is only one example of many in the past century. In this thesis, I analyzed the aspects of viral composition and communicability and the scope of appropriate treatment methods and vaccine candidates and how German cultural and scientific perspectives influence research approaches. One goal included researching the breadth and depth of viral knowledge—specifically pathophysiology and activity of the virus—and reactions of both cultures towards the pandemic. Although COVID-19 closely correlates to SARS-CoV-2, research was limited to SARS-CoV-2 because there is a natural division between them. The questions currently being asked by scientists will most likely change the course of pandemics in the future, which is crucial as the question is not “if” but “when” the next pandemic will come.

Title of Work (IGP Language): SARS-CoV-2: wie die Pathophysiologie des Virus den Umfang der Impfstoffmethoden aus der deutschen wissenschaftlichen und kulturellen Sicht beeinflusst

Abstract (IGP Language): Eines der wichtigsten Probleme im Gesundheitswesen sind wohl Viren, die die potenziellen weitverbreiteten Krisen auslösen. 2020 ist SARS-CoV-2 die Ursache der derzeitigen Pandemie und nur ein Beispiel im letzten Jahrhundert von vielen. In dieser Bachelorarbeit wurden die Aspekte viraler Zusammensetzung und deren Kommunizierbarkeit und der Umfang der geeigneten Behandlungsmöglichkeiten und Impfstoffmethoden erforscht und es wurde auch untersucht, wie deutsche kulturelle und wissenschaftliche Perspektiven die Forschungsherangehensweise beeinflussen. Eines der Ziele war, die Breite und Tiefe der Reaktionen auf die Pandemie und das virale Wissen, nämlich das Wissen über die Pathophysiologie und Aktivität zu untersuchen. Obwohl COVID-19 eng mit SARS-CoV-2 zusammenhängt, wurde die Forschung auf SARS-CoV-2 begrenzt, weil es eine natürliche Trennung dazwischen gibt. Die Forschung und Fragen, die Fachleute momentan stellen, werden höchstwahrscheinlich die Herangehensweise an und den Umgang mit Pandemien in der Zukunft ändern, was entscheidend ist, da die Frage nicht ,,ob” ist, sondern ,,wann” die nächste Pandemie kommen wird.

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Elevator Pitch Transcript: Hi! My name is Skylar Weber and I am majoring in both Biomedical Sciences and German. Last year, I studied for six months in Constance, Germany—a beautiful town on the coast of Lake Constance near the border between Germany and Switzerland. When the pandemic spread worldwide, I was required to return to the States, reconfiguring my internship experience from lab-based research to a comparative and interdisciplinary research project about the severe acute respiratory coronavirus 2, widely known as SARS-CoV-2. As a result of the viral structure, communicability, and spread among communities, this novel pathogen has impacted the lives of millions globally—but some countries more than others. Once the virus has infected an individual, the impending damage of various connective tissues and organs and the disease it causes serves as clues to possible treatment modalities and prevention strategies for those not yet infected. Scientists around the world have been and continue to work tirelessly in labs to translate the immune response into possible, much-needed vaccine therapies. During my presentation, I will further explain these various biomedical components in relation to the novel coronavirus and will emphasize how German scientists and the population have reacted to and fought against the inevitable in Germany, leading to testing promising vaccine candidates in clinical trials and a population not only determined in limiting the community spread of the coronavirus, but virtually eradicating its presence from their cities. SARS-CoV-2 has and will continue to affect the lives of all of us worldwide, yet operating within other cultural frameworks with an emphasis on differing morals and values could mean the successful navigation of the unfortunate crisis this pandemic has caused. I invite you to watch my full presentation and am looking forward to answering all of your questions during the Q&A sessions. Hope to see you there!

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Full-Length Video Transcript: Hello! My name is Skylar Weber and the title of my IGP research project is, SARS-CoV-2: how the pathophysiology of the virus influences the scope of vaccine methods from a German cultural and scientific perspective.

The presentation of my research project will be divided into three main parts: the introduction, research of the project, and linguistic and cultural acquisition. First, I will give a summary with background information and my personal motivation for this project. Then, I will discuss the structure, pathophysiology and mechanisms of infection of the SARS-CoV-2 virus and a vaccine possibility against the virus, BNT162, for example. Then, we will come to the conclusion, during which I will present perspectives for the future, and finally, I will discuss my observations, experiences, and findings of my linguistic and cultural acquisition in Germany.

A 33 year old, otherwise healthy, German businessman (Patient 1) became ill January 24th with a sore throat and chills and had a fever with a productive cough the next day. On January 27th, he felt better again and returned back to work. During this time, in which he did not have any symptoms (he was presymptomatic), he attended business meetings and came in contact with the index patient. The index patient, a business partner and Shanghai resident, visited Germany from January 19th to January 22nd and did not have symptoms her entire stay. Although she did not have symptoms when she was in Germany, she developed various mild symptoms on the flight back to Shanghai. First, she was labeled asymptomatic, but after further interviews, it became more clear she was oligosymptomatic, or more specifically mildly ill with unnoticeable symptoms. Patient 1, who was positive, was tested many times, in order to confirm his viral load. His viral load was very high with 10^8 viral copies per milliliter in his sputum both when he had symptoms and throughout the days thereafter, even though his symptoms had subsided. Patient 2 only had contact with the index patient, and Patients 3 and 4 only had contact with Patient 1. In this situation, it became clear the transfer of the virus is possible during the incubation time of the index patient. All of these patients had mild and unspecific illnesses and showed prolonged viral shedding is possible, also when people have no or mild symptoms.

When I began this project in April, I had many questions, which I found not only interesting, but particularly relevant this year. In my presentation, I will try to explain and answer the questions: how and why are viruses very virulent and life-threatening, in general, particularly the SARS-CoV-2 virus; and which effects does the pathophysiology and various cultural backgrounds on reactions against the pandemic and on vaccine developments and methods. Public health is especially important because their goal is to protect and improve the health of communities. I have great interest in this field as I strive to become a physician.

Next, we have the research of my project. For this project, I used a variety of difference sources including: scientific articles both published and pre-prints, podcasts from virologists and scientists in general, and personal interviews with both of my German friends and other IGP-students.

For this presentation, the spike proteins of the SARS-CoV-2 virus important and I’ll explain why. While all parts of a virus have a specific job, helping the virus to infect immunologically naïve individuals and to survive and replicate itself in the body’s own cells, the spike protein of SARS-CoV-2 are of particular importance. Spike proteins (S1 and S2) are located on the surface of viral cells and play a crucial role in which the SARS-CoV-2 virus has both the ability and opportunity to enter the lungs and the lung alveoli in severely ill individuals. Angiotensin converting enzyme 2 (ACE2) receptors are on the surface of type 2 pneumocytes to which the virus can bind through the receptor binding domain (RBD) on its spike proteins and with the help of the transmembrane serine protease 2 (TMPRSS2) enzyme. After the cells of the virus have docked on the ACE2 receptors, it is then possible for the virus to penetrate the pulmonary alveoli and become the cause of COVID-19 disease.

When an infected individual coughs, sneezes, and breathes, they release viral-containing droplets in to the air, which can infect another person through inhalation. The inhaled viral particles will travel through the trachea and bronchi of the lungs, eventually invading the pulmonary alveoli, specifically the type 2 pneumocytes, by binding to the ACE2 receptors on the alveolar cell surface. Once inside the type 2 pneumocyte, the viral cell self-replicates with help from the host cell, leading to the release of many more virulent viral cells into the alveolus and the body with the potential to infect another person or multiple people. Simultaneously, the virus is recognized as foreign, which leads to the recruitment of inflammatory mediators such as neutrophils to the alveolus. The presence of neutrophils further recruits macrophages, leading to the release of inflammatory cytokines—IL-1, IL-6, TNF-alpha, etc.—into the blood stream. Because of this phenomenon, vasodilation and an increase in blood vessel permeability occurs and the inflammatory cytokines will travel to the brain and signal the hypothalamus to release Prostaglandin E2 (PGE2) resulting in a fever. Due to the leakiness of the blood vessels, the pressure of oxygen will decrease signaling the sympathetic nervous system (SNS) to respond which will ultimately increase both heart and breathing rates. The continued response from the innate immune system via continued secretion of inflammatory cytokines will eventually hinder the alveolus from functioning properly, resulting in difficulty breathing due to an accumulation of fluid and systemic inflammatory response syndrome. This syndrome could lead to multi-organ failure as blood pressure, circulating blood volume, and perfusion all significantly decrease.

The mechanism of the pathophysiology is central to understand in order to develop an effective vaccine against the virus. Vaccine development describes procedures for the targeted adaptation of inoculants and also uses methods of protein and vector models, in order to achieve long-lasting protection for an illness or infection. By and large, a vaccine model must follow methods to optimize the immune response. To be successful, a model must first identify antigens to be used in a vaccine with different epitopes on which the adaptive immune response can bind. The chosen vaccine model partly depends on the details and components of a virus. The various vaccine models are as follows: inactivated, attenuated, synthetic peptides, recombinant subunits, DNA, recombinant bacterial and recombinant viral vectors.

The vaccine BNT162, currently being researched and tested in clinical trials by Pfizer and BioNTech, is an mRNA-based vaccine design. Using an mRNA-vaccine, if adequately effective, is paramount to this pandemic as this vaccine has a shorter and more simplistic production process that is fast, flexible, and scalable, accounting for the current global need. To create this vaccine, only the genetic code of the viral antigen is produced instead of producing the entire viral antigen before injecting the material into an immunologically naïve individual. After the injection, the body’s own cells will take over the production process of the antigen, producing antigens that immune cells will ultimately recognize as foreign and build protection against. During this process, the innate immune system will be stimulated, the newly-created target molecules will be presented and expressed on the cell surface, the adaptive immune system will be activated, the number and repertoire of antigen-specific T- and B-cells will expand, and finally, both a proportionate cellular and humoral immune response will be induced. This vaccine method injects neither an activated nor an inactivated form of the virus, but rather uses the cell machinery to build the antigen, the spike protein of the SARS-CoV-2 virus, so that the body can build immunity before ever coming in contact with the original, virulent virus.

Because the pandemic was caused by a novel virus in an immunologically naïve population, it seems, as if there are more questions instead of answers as scientists, researchers, and medical professionals learn something new almost every day. Research with the BNT162 vaccine development will continue in Phase II/III clinical trials since the Phase I/II clinical trials had shown a strong immune reaction because of the vaccine. One hope for the future is that we will learn more through secondary outbreaks in many countries. Whether the immunological memory influences the symptoms during a second infection and which immune reactions are important for maintaining immunity are both crucial, especially for current and future vaccine research and development.

Currently, as of September 20, 2020, there at least five documented cases of reinfection in the world, which are located in Hong Kong, Nevada, Belgium, the Netherlands, and Ecuador, meaning these individuals have already survived and infection with SARS-CoV-2 and then got infected again. Virologists worldwide do not yet know what reinfection means for the future except that there is the possibility. Therefore, three important questions remain: first, how common is reinfection; second, is reinfection more or less severe than the first; and lastly, what impact does reinfection have on vaccine prospects? A more accurate and reliable perspective could only emerge with time, not only to answer these questions correctly, but rather whether or not a vaccine candidate and the immune system have the answers in order to end the pandemic. There is only single way out of the pandemic to date, which is through further research and learning about the virus.

Lastly, the linguistic and cultural acquisition section of my presentation.

Between American and German culture, there are many similarities I noticed during the first month in daily life and at the university in Constance. My first impressions in relation to my linguistic observations are as follows: within friend circles, there are regular fact-based and interesting discussions about international and current events, including discussions, in which the students discussed educated explanations of complex themes and processes. It happened more often in comparison to discussions between friends here in the USA in my experience. Although I understood the various discussions, I could not participate in German until a few months later, because my vocabulary was not as broad. Regarding cultural observations, both cultures have more individualism instead of collectivism and more masculinity instead of femininity, according to Hofstede Insights and my experiences, but American culture is, according to Hofstede Insights, more individualistic and more masculine than German culture. During that time, I thought the difference between the cultures is not large, but with the pandemic and the measures taken in both countries, it became clear to me which parts of these cultural components both cultures value.

During the pandemic, it became clearer the United States of America are more individualistic than Germany and has higher indulgence as a population. As Americans, we need information about the virus and the pandemic in order to make decisions for our family, rather than for our community and the entire population. We make changes in our life as long as they do not have a negative effect on our happiness and if we can still do as we please. In Germany, it is almost the exact opposite because Germans, in various contexts, are not as individualistic, have higher long-term orientation, and search for scientific-based information in order to make decisions and follow realistic and valuable actions to protect the community from the SARS-CoV-2 virus. Of course, there are exceptions in both countries and cultures.

In these pictures, we can see various definitions of freedom. When the people in Germany were under quarantine for months, Germany had more control and contained the cases of infection of the pandemic in comparison to the USA. For the larger idea of protecting the community and preparing the hospital systems, the people followed the scientifically-based and suggested actions under the motto of “we can do it,” and because of that are able to lead their lives with less worry about a possible infection of the SARS-CoV-2 virus. In many places in the USA, people do not believe in the measures suggested by public health institutions and have, instead, protested against the recommendations. For many in the USA and for the minority of protestors in Germany, the question remains: are the measures, in order to defeat the virus and to end the pandemic, an abuse of human rights or an opportunity and the realistic possibility to protect the community and to contain the cases of infection?

Here, we can see the results of different cultures and the results of the different actions taken by the governments against the pandemic. Although the populations and the governments of both countries had and continue to have polar opposite reactions towards the virus and the pandemic, both the more hopeful American scientific community and the more pragmatic German scientific community are researching towards a common goal: a solution or a vaccine candidate that will end the pandemic.

While abroad and while researching for this project, I did not only learn about the virus, but about myself, and also expanded my identity, combining attributes of both cultures into my daily life and the way I approach topics and problems. Similar to my linguistic and cultural development, the solution for this pandemic is going to be multi-faceted and require the opinions from multiple cultural backgrounds. To align with mainstream media and believe Americans can resolve this alone is not only ill-informed, but selfish, as it is going to take a global effort to defeat this global crisis.

Many thanks to the Interdisciplinary Global Program, Professor Jessica Wood, Dr. Michael Ort, Katja Kümmerlen, Alina Knaupp, and my family, who have all helped me to make my project possible and successful.

Do you have any questions? Simply ask me during the question and answer sessions on November ninth on Zoom!

Here are the sources for the pictures I used.

Thank you very much for watching!

Keywords

SARS-CoV-2, coronavirus, vaccine, BNT162, public health, immunology, virology