The Heinsberg Study:
Bonn-based research team determine COVID-19 infection fatality rate
May 4, 2020
The district of Heinsberg in the German state of North Rhine-Westphalia is considered a hot spot for the novel Coronavirus SARS-CoV-2. Following a carnival celebration, the district became one of the first areas in Germany where the pathogen spread and infected large quantities of people. As part of the study, a research team led by Prof. Dr. Hendrik Streeck and Prof. Dr. Gunther Hartmann from the University of Bonn carried out a large study to precisely determine the infection fatality rate for the first time among other findings. The results of the study have been pre-published and are now presented to scientists and the public. Publication in a peer-reviewed journal is to follow.
The focus of the study is the infection fatality rate (IFR), which indicates the ratio of deaths in comparison to those infected. The IFR is different to the case fatality rate (CFR). For various reasons, the IFR is considered the more reliable parameter and there is an international demand to have a more accurate understanding of the fatality of SARS-CoV2. “For the first time, our data enables us to estimate how many people have been infected after the superspreading event. Approximately 15 percent of Gangelt had been infected. The total number of infections allows us to determine the infection fatality rate. In Gangelt, the IFR after the SARS-CoV-2 outbreak is 0.37 percent,” says lead investigator Prof. Dr. Hendrik Streeck, Director of the Institute for Virology at the University Hospital Bonn.
Based on the IFR and the number of deaths, estimations about the total number of infections in similar demographic areas with different infection rates can be made. Comparing this number with the number of officially reported infections leads to an estimate of unreported cases. In Gangelt, this figure is about 5 times higher than the official number of people tested positive. With an extrapolation based on 6,700 SARS-CoV-2 associated deaths in Germany, a total of 1.8 million infections can be assumed. This number of unreported cases is about 10 times higher than the officially reported cases (162,496 on May 3rd, 2020).
“The results can be used to further improve models on the transmission behavior of the virus. Until now, the basis for such data has been relatively uncertain,” says co-author Prof. Dr. Gunther Hartmann, Director of the Institute for Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn and speaker of the Cluster of Excellence, ImmunoSensation. The study also provides important indicators for further research on SARS-CoV-2 such as the infection risk dependent on age, gender, and pre-existing conditions; the increased severity of illness amidst special circumstances of a massive infection incident such as in Gangelt, or on the risk of infection within families.
22% of COVID-19 infections are completely asymptomatic
The description of the symptoms is another aspect the study covers. Loss of smell and taste, as previously identified by Prof. Streeck, are the most striking symptoms of this infection. Interestingly, 22 percent of infected persons in Gangelt were asymptomatic. People who participated in the carnival event had more often symptoms. “To examine if physical proximity to participants of the carnival event and the increased aerosol formation through loud speaking or singing lead to a more severe disease progression, we are planning further studies in cooperation with hygiene specialists,” explains Prof. Hartmann.
“One in five infections occurs without noticeable symptoms strongly suggests that infected persons who secrete virus and can infect others cannot be reliably identified based on recognizable symptoms of the disease,” says Prof. Dr. Martin Exner, head of the Institute for Hygiene and Public Health and co-author of the study. This confirms the importance of general rules of distance and hygiene in the corona pandemic. “Every supposedly healthy person we encounter can unknowingly carry the virus. We must be aware of this and act accordingly,” says the hygiene expert.
Studies of multi-person households showed that the risk of infecting another person was surprisingly low. “The infection rate in children, adults and elderly is very similar and is not dependent on age,” says Prof. Streeck. There are also no significant differences between genders.
A total of 919 participants from 405 households
A total of 600 randomly selected households in Gangelt were written to and asked to participate in the study. 919 study participants from 405 households were interviewed and tested between March 30th and April 6th, six weeks after the outbreak of the infection. Researchers took throat swabs and performed blood tests. In the acute phase of the infection in the first one or two weeks, the PCR test, which captures the genetic thumbprint of SARS-CoV-2, is very reliable. Two or three weeks after the infection takes place, the immune system builds antibody responses against the virus, which can be detected by ELISA.
“By combining PCR (very specific) and ELISA (very sensitive but with false positive) tests we can detect acute as well as elapsed infections,” says Prof. Hartmann. Preliminary studies showed that the ELISA test is falsely positive in about one percent of the cases. “However, with such high frequency of infections in Gangelt, a one percent false positive rate is not critical,” Hartmann explains.
Very important to remember that in locations with many people, if there is good ventilation, infection rates are very low or even not measurable.
How significant are the results?
Prof. Gunther Hartmann: “The estimated percentage of infected individuals only refers to the town of Gangelt and its specific situation with the super spreading event. It is not representative of other areas in Germany. However, the infection fatality rate is a number that is very helpful to improve model calculations. For example, with all the uncertainties in mind, the IFR applied to 6,700 SARS-CoV-2-associated deaths currently registered in Germany would lead to an estimate of 1.8 million infections in Germany, which is approximately ten-fold higher than the reported number. Thus, our results can be utilized to further improve models on the pandemic. Here, our data contribute important additional information.”
What was the focus of the study?
Prof. Hendrik Streeck: “Following a carnival event in Gangelt in the district of Heinsberg, the district became the first area in Germany with a massive COVID-19 outbreak. We started to examine infected persons and their environment. On this basis, end of March 2020, I met with other scientists in Bonn and we developed a plan to systematically study the number of infections in the community of Gangelt, the local hotspot.”
What are the most important results of the study?
Prof. Hendrik Streeck: “The focus of the study is to determine the number of infected, and the infection fatality rate (IFR), which indicates the ratio of deaths in comparison to those infected. Based on the data, we could calculate for the first time that the IFR in the context of the SARS-CoV-2 outbreak is 0.37 percent. If corrected for additional factors, this figure varies between 0.24 and 0.43 percent. About 15 percent of all persons examined tested positive for SARS-CoV-2. The officially reported infection rate for the community of Gangelt at the time of the study was 3 percent. This means that the real number of infections in Gangelt is about 5-fold higher than the official number. Single-person, as well as multi-person households, were studied to analyze a family cluster effect. The study shows that the probability of infection of a study participant is independent of the household size the person lives in. However, in a household with at least one person infected, the probability of infection for the other persons increases over the average of 15 percent (e.g. the additional risk of infection in a 3-person household is approximately 20 percent). The infection rate in children, adults, and the elderly do not differ significantly. However, children had a lower infection rate, but due to the relatively low number of children in the study, we don´t know yet whether this difference is statistically significant. The study also demonstrates that participation in carnival events (a super-spreading event) enhanced the infection rate and the number of symptoms.”
“Which conclusions can be drawn from the study results depends on many factors that go beyond pure scientific considerations,” says Prof. Streeck. “The evaluation of our findings and their impact on concrete decisions are the responsibility of society and politics.”
In the SARS-CoV-2 pandemic, exceptional rules also apply for scientific publishing. Renowned scientific journals require that papers on the topic of Covid-19 are first uploaded to a preprint server and thus made available immediately to science and health authorities (https://wellcome.ac.uk/coronavirus-covid-19/open-data). Only following this step, the normal publication process by peer review takes place.
Can you tell us anything about the course of the infection and the severity of symptoms?
Prof. Hendrik Streeck: “A total of 22 percent of those infected showed no symptoms at all. People who participated in a carnival event were more often infected with SARS-CoV-2 and showed more severe symptoms than people who did not participate in such events. It is possible that the viral load upon initial infection was higher at carnival events.”
How many people were tested positive for the virus?
Prof. Hendrik Streeck: „In April 2020, 14 percent of those tested in Gangelt already carried antibodies against the virus. Viruses were only detected in a small fraction of study participants (2,4 percent).”
To which extent can you exclude confusing the SARS-CoV-2 with common cold coronaviruses?
The high specificity of the ELISA and the PCR means that other coronaviruses are not detected. There is cross-reactivity with SARS-1, but this virus was never present in Germany. Besides, we carried out neutralization assays. To verify, we examined blood samples of patients tested positive for other coronaviruses, taken before the outbreak of the current pandemic, which all were negative.
Which results did you obtain on infection rates in private households?
Prof. Martin Exner: “In private households with one member carrying the virus, the risk of infection for other members of the household is increased. For example, the risk of infection in a 3-person household is increased by 20 percent. The rates of new infections in children, adults, and elderly people are not significantly different but are somewhat lower in children, but the numbers of children in this study are too small. There are also no differences between genders.”
Prof. Hendrik Streeck: “There is no information on the actual cause of death of patients who were tested positive for COVID-19.”
Are these findings representative for Germany, other countries, and the world?
Prof. Hendrik Streeck: “We are dealing with a so-called super-spreading event, which is why our findings can only to a limited extent be applied to the rest of Germany or other countries. Nonetheless, the data we have collected on this event offers important scientific starting points because infections in Gangelt occurred very early and vigorously compared to the rest of Germany. Our findings can be used to improve models simulating the spread of the virus, for example.”
What use does your study have for science, politics, and society?
Prof. Hendrik Streeck: “The Heinsberg Study is the first to collect extensive data on the occurrence of COVID-19 infections in a hot spot. The study offers starting points for follow-up research. The Robert Koch Institute, the Charité in Berlin, the University of Munich (LMU), and the Helmholtz Association are now conducting studies with a similar approach.”
Publication:
“Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event“
By Hendrik Streeck, Bianca Schulte, Beate M. Kümmerer, Enrico Richter, Tobias Höller, Christine Fuhrmann, Eva Bartok, Ramona Dolscheid, Moritz Berger, Lukas Wessendorf, Monika Eschbach-Bludau, Angelika Kellings, Astrid Schwaiger, Martin Coenen, Per Hoffmann, Birgit Stoffel-Wagner, Markus M. Nöthen, Anna-Maria Eis-Hübinger, Martin Exner, Ricarda Maria Schmithausen, Matthias Schmid and Gunther Hartmann