Munich Tropical Institute starts cohort study to investigate the spread of the corona pandemic and the effectiveness of countermeasures

Copyright: Munich Tropical Institute

All over the world, and thus also in Munich, people are currently in the midst of an unprecedented situation. They are directly or indirectly confronted with the consequences of the COVID 19 pandemic and experience how "social distancing" or "self-isolation" determine their everyday life. They keep their distance from each other in public space and only meet relatives or friends virtually. They do this to protect themselves and others from the spread of the novel coronavirus and to ensure medical care, especially for the most severely affected patients.

Representative sample of Munich households
But to what extent will the COVID 19 pandemic continue to keep us in suspense and what is the effectiveness of the countermeasures? Experts are calling for better data to be made available in order to be able to assess this. The Tropical Institute at the LMU Klinikum München (Department of Infectious and Tropical Medicine) recognized this need early on and, together with the Bavarian State Government, prepared the project "Prospective COVID-19 Cohort Munich" (KoCo19 for short). It is planned to visit up to 3,000 representatively selected households in the Munich area at various intervals, to examine the state of infection among the study participants and to collect further health information.

Joining forces with the Munich research community
In order to analyze the spread of SARS-CoV-2 in the population, cooperation partners from the Center for International Health (CIH), the Institute of Occupational, Social and Environmental Medicine and the Institute for Emergency Medicine and Medical Management (INM) of the LMU Klinikum, as well as Helmholtz Zentrum München are working together under the leadership of the infectious disease physician and director of the Tropical Institute, Prof. Dr. med. Michael Hölscher. In addition to analyzing the spread of the virus, antibody tests will also be used to determine how many people have already become infected with the virus without ever having experienced symptoms. This is because they too can transmit SARS-CoV-2 and thus promote the pandemic. In addition, it is important to determine the time interval during which the disease spreads within the household.

Aid for political decision-making
The effectiveness of current measures (e.g. the avoidance of social contacts or mobility restrictions) can be better assessed with the help of this study. Bavarian Minister-President Dr. Markus Söder affirms: "The KoCo19 study can help politicians to better assess the dynamics of the pandemic and thus make the best possible decisions based on facts. For this reason it is important to collect data on the Bavarian COVID-19 situation in a timely manner". A study with randomly selected households is the gold standard of such epidemiological studies. Of course, this is not possible for all of Germany or Bavaria. However, the generated data should continue to be used to "calibrate" simpler methods such as cross-sectional studies or examinations of blood donors, and then make them available for the whole of Bavaria.
Minister of Science Bernd Sibler emphasized: "With team spirit against Corona - 100 scientists from Bavaria and about 70 medical students from our universities have joined together in the last two weeks to form an interdisciplinary team and prepared themselves quickly and professionally for this project. This pioneering alliance of scientific expertise in the Free State gives me great hope. Together we are working to better understand this virus, to fight it effectively and to emerge successfully from this crisis!

From antibody tests to diaries
In order to be able to make such predictions, the study includes people of all age groups from the total population of Munich. The researchers randomly select 3,000 Munich households and invite them to participate in the study. All household members over the age of 14 years will be interviewed in person and asked for a blood sample to determine antibodies against SARS-CoV-2. In case of current symptoms, a throat swab can also be taken. In addition, each household member can voluntarily keep a symptom, whereabouts and contact diary via app.

This should be repeated several times over a period of about twelve months. If typical symptoms of SARS-CoV-2 occur between visits to the household members, it is possible to have a nasopharyngeal swab taken at the Tropical Institute of the LMU Klinikum München between the scheduled appointments. This can be used for molecular detection of an acute coronavirus infection. In case of severe symptoms, admission to a Munich hospital will follow.

From Sunday 05 April 2020, the first medical teams of the study will be on the road in various parts of Munich. Prof. Michael Hölscher, Director of the Tropical Institute at LMU Klinikum München, calls on Munich residents to participate: "In order to be able to counter the pandemic smartly, we must be able to understand the spread of SARS-CoV-2 and estimate exactly how many people have already successfully survived the infection. In the coming months, this will be one of the most important parameters for managing social distancing measures. Representative samples are a good instrument for this purpose".

"The instant organization of this cooperation, to which, for example, our best brains for modeling in artificial intelligence contribute, shows the functioning cooperation of top medical research in Munich", says Prof. Dr. med. Matthias Tschöp, CEO at Helmholtz Zentrum München.

About the study:
The project is funded by the Bavarian State Ministry of Sciences and Arts, LMU Klinikum and Helmholtz Zentrum München.

The results of the study are regularly discussed in an advisory committee consisting of the Bavarian State Ministry of Science and Art, the Bavarian State Ministry of Health and Care, the Department of Health and Environment of the City of Munich, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München.

Project team:
Head: Tropical Institute, LMU Klinikum München (Division of Infectious Diseases and Tropical Medicine)

Project partners:
•    Center for International Health, LMU Klinikum
•    Institute for Occupational, Social and Environmental Medicine, LMU Klinikum
•    Institute for Emergency Medicine and Medical Management (INM), LMU Hospital
•    Helmholtz Zentrum München

The research project includes accompanying studies, which are carried out in cooperation with the laboratory Becker & Colleagues and the blood donation service of the BRK (Bavarian Red Cross).

We thank the Munich police for their friendly support.

We are grateful to Mercedes-Benz Munich, which supports us with their car rental Mercedes-Benz Rent in the project infrastructure.

Current information on the study will be announced at:

Frequently Asked Questions (FAQ):

What are the benefits of participating in the study?
If you develop symptoms compatible with a SARS-CoV-2 infection during participation in the study, you have the option of having a nasopharyngeal swab test performed at the Tropical Institute, LMU Klinikum München. In case of an acute infection with the novel coronavirus you will be informed immediately and in case of severe symptoms you will be admitted to a Munich hospital.
The tests performed in the study will tell you whether you have already been infected (possibly undetected) with SARS-CoV-2 and have developed antibodies against it. In the course of the study, additional testing of these antibodies is also planned in order to better assess the possible protective effect.

By participating, you can make an active contribution to combating this pandemic. The new scientific findings help to control the "social distancing" measures in such a way that we do not overburden our hospitals and at the same time do not restrict social life to an excessive degree.

Who can participate and how does the study work?
For the study, randomly selected and representative participants (cohort) of all age groups from the total population of Munich are chosen. This is done according to the so-called random route method. For this purpose, 100 of the 755 Munich constituencies were randomly selected. Starting from the geographical centre of these 100 constituencies, the study teams follow a route determined in advance according to an algorithm, along which they include 30 households.

Regardless of whether you are known to be infected with the novel coronavirus (SARS-CoV-2) or not: in both cases you are a potential study participant. The study will also examine how many people had not even noticed that they were infected with the virus.

If your household is selected, a mobile study team will visit you personally and provide flyers and information material. You can comfortably decide at home whether you want to participate or not. If you have any questions, you can discuss them directly with the team on site. On the day the flyers are distributed, the selected households can leave a telephone number for the study teams so that they can be informed in the following days before the planned test date. The telephone number will not be given to third parties, but will be kept confidential.
If you have decided to participate, all household members over the age of 14 years in your household will have the opportunity to be interviewed in person and give a blood sample for the determination of SARS-CoV-2 antibodies. This should be repeated several times over a period of approximately 12 months. Each household member (including possible children, filled in by the adults) is asked to keep a symptom, whereabouts and contact diary via app.

Does participation entail any risk for me?
By participating, you are exposed to very low health risks at best. Our medically trained personnel follow the patient safety guidelines of the Robert Koch Institute during "home visits" in order to provide maximum protection. The team is trained in venous blood sampling and patient interviews. Protective clothing and infectious materials are of course changed and safely discarded after each visit to a study participant.

The mobile team observes the currently recommended distance rules and protective measures and travels by car, not by public transport. The student team clearly identifies itself as such, so that you can be sure that if you grant our team access to your home, you will be safe. Your patient data will be treated confidentially in accordance with the provisions of the German Data Protection Ordinance (DSGVO).

Participation in the study is voluntary. You can revoke your respective consent at any time in writing or verbally without giving reasons and without incurring any disadvantage.

Does the study tie up testing capacity or medical staff that would be needed elsewhere?
No. The study does not provide any test options that would otherwise be available to other acutely ill patients. The testing performed in this study is not intended for acute diagnosis and care, but only examines past SARS-CoV-2 infections. In addition, the study will only employ additional medical personnel who are not involved or planned in the acute care of COVID-19 patients. We would like to take this opportunity to thank everyone who has agreed to support the research project at such short notice.

How does the evaluation work and when can results be expected?
We want to thank you for your willingness to participate in our study as one of the randomly selected households. The recruitment of the 3,000 households (approx. 5,000 - 6,000 individuals) in Munich is expected to be completed by mid June 2020. Until then, all participants will have blood samples taken and their basic personal information collected via questionnaire on the web app. As a participant your health will be monitored via regular blood tests, which will take place at regular intervals for several weeks and surveys which will continue over the entire duration of the study.
The detection of antibodies against the new SARS-CoV-2 is a sign of a surviving infection. In order to test for this, serological tests —so-called enzyme-linked immunosorbant assays (ELISA)— are currently being carried out in the KoCo19 laboratory at the Division of Infectious Diseases and Tropical Medicine, in Munich. Even though the available antibody tests already have a very high specificity (over 98%), they still have an error rate of approximately two to three percent. This means that for every 100 tests there are at least two unspecific reactive results (often simply referred to as “false positive”): where a sample shows as positive despite there not being any SARS-CoV-2 antibodies (or infection) present. This small rate of unspecific reactive results can lead to massive statistical bias in relation to the overall result. After completing the first antibody tests in the KoCo19 study, we estimate that the prevalence could be in the low single digits.
To get meaningful results —i.e. to describe how many people have actually been infected with SARS-CoV-2— the results must be confirmed through additional tests. For this purpose, a so-called neutralization test is carried out on cell cultures for SARS-CoV-2 there is currently no routine procedure for this. The neutralization test provides information as to whether the detected antibodies in the blood actually make the novel coronavirus harmless. Moreover, the ability to rely on any one test result will also increase through repeated testing of the participants over the course of the study. In order to carry out a more precise determination, we also carry out further complex tests: tests for other circulating coronaviruses can provide information on the cross-reactivity of antibodies and tests using “peptide arrays”, which can provide information on which structures of SARS-CoV-2 exactly dock the antibodies detected, are two such examples.
In order to be able to make reliable statements and increase the certainty regarding the exact data of the overall KoCo19 cohort, we ask you to be patient. We will communicate the interim results of the first survey phase of KoCo19 to the public as soon as the aforementioned steps have been completed.

Additional information: Deutsche Welle interview with Professor Hoelscher (April 2020)

Version: 28.04.2020, subject to modifications.