Ten times more people than previously thought may have already acquired immunity to the coronavirus.
The Daily Telegraph reports that this is according to scientists from the University of Bonn who claimed their findings show that 1.8m people across Germany have already been infected with the virus. That is more than ten times as many as have tested positive so far, and would mean more than 1.6m may have been infected and recovered without knowing it.
The report says the findings are based on the first comprehensive study of the effects of the virus on a single community in Gangelt, the town at the epicentre of Germany’s first major outbreak.
The study’s authors now believe that 0.37% is the general fatality rate for the virus and that it can be used to extrapolate the total number of undetected infections from the death toll. “Because our research allows us to determine exactly how many individuals are infected, we can also determine the percentage of deaths among all those infected with great accuracy,” Professor Hendrik Streeck, the study’s leader.
It is still not clear whether those who recover from the virus have any form of immunity, or how long it may last, Streeck is quoted in the report as saying “But we can draw conclusions from the laboratory,” he said. “Trained immune responses can block the virus, and we know in the case of other corona viruses that you can have at least partial immunity.”
But, the report says, the Gangelt study has proved controversial in Germany. Rival scientists have questioned its methodology and they were quick to cast doubt on the findings. Professor Gérard Krause of the Helmholtz Centre for Infection Research pointed to the fact only seven people are known to have died of the virus in Gangelt. “That means one death more or less would make a really significant difference to the study,” he said.
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 Professor Hendrik Streeck and Professor 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.
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 super-spreading event. Approximately 15% 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%,” says 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 positively. 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 behaviour of the virus. Until now, basis for such data has been relatively uncertain,” says Hartmann, director of the Institute for Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn. 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.
The description of symptoms is another aspect the study covers. Loss of smell and taste, as previously identified by Streeck, are the most striking symptoms for this infection. Interestingly, 22% of infected persons in Gangelt were asymptomatic. People who participated in the carnival event had more often symptoms. “In order 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 Hartmann.
“Apparently one in five infections occurs without noticeable symptoms suggests that infected persons who secrete virus and can infect others cannot be reliably identified on the basis of recognizable symptoms of the disease,” says Professor 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 apparently not dependent on age,” says Streeck. There are also no significant differences between genders.
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 30 March and 6 April, 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 and ELSIA tests we are able to detect acute as well as elapsed infections,” says Hartmann. Preliminary studies showed that the ELISA test is false 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.
For studies planned to take place across Germany with an estimated infection rate of approximately one to two percent a one percent false positive rate pose rather a problem. “Which conclusions can be drawn from the study results depends on many factors that go beyond pure scientific considerations,” says Streeck. “The evaluation of our findings and their impact on concrete decisions are the responsibility of society and politics.”
Abstract
The world faces an unprecedented SARS-CoV2 pandemic where many critical factors still remain unknown. The case fatality rates (CFR) reported in the context of the SARS-CoV-2 pandemic substantially differ between countries. For SARS-CoV-2 infection with its broad clinical spectrum from asymptomatic to severe disease courses, the infection fatality rate (IFR) is the more reliable parameter to predict the consequences of the pandemic. Here we combined virus RT-PCR testing and assessment for SARS-CoV2 antibodies to determine the total number of individuals with SARS-CoV-2 infections in a given population.
Methods: A sero-epidemiological GCP- and GEP-compliant study was performed in a small German town which was exposed to a super-spreading event (carnival festivities) followed by strict social distancing measures causing a transient wave of infections. Questionnaire-based information and biomaterials were collected from a random, household-based study population within a seven-day period, six weeks after the outbreak. The number of present and past infections was determined by integrating results from anti-SARS-CoV-2 IgG analyses in blood, PCR testing for viral RNA in pharyngeal swabs and reported previous positive PCR tests.
Results: Of the 919 individuals with evaluable infection status (out of 1,007; 405 households) 15.5% (95% CI: [12.3%; 19.0%]) were infected. This is 5-fold higher than the number of officially reported cases for this community (3.1%). Infection was associated with characteristic symptoms such as loss of smell and taste. 22.2% of all infected individuals were asymptomatic. With the seven SARS-CoV-2-associated reported deaths the estimated IFR was 0.36% [0.29%; 0.45%]. Age and sex were not found to be associated with the infection rate. Participation in carnival festivities increased both the infection rate (21.3% vs. 9.5%, p=0.007). The risk of a person being infected was not found to be associated with the number of study participants in the household this person lived in. The secondary infection risk for study participants living in the same household increased from 15.5% to 43.6%, to 35.5% and to 18.3% for households with two, three or four people respectively (p< 0.001).
Conclusions: While the number of infections in this high prevalence community is not representative for other parts of the world, the IFR calculated on the basis of the infection rate in this community can be utilized to estimate the percentage of infected based on the number of reported fatalities in other places with similar population characteristics. Whether the specific circumstances of a super-spreading event not only have an impact on the infection rate and number of symptoms but also on the IFR requires further investigation. The unexpectedly low secondary infection risk among persons living in the same household has important implications for measures installed to contain the SARS-CoV-2 virus pandemic.
Authors
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
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[link url="https://www.uni-bonn.de/news/111-2020"]University of Bonn material[/link]
[link url="https://www.ukbonn.de/C12582D3002FD21D/vwLookupDownloads/Streeck_et_al_Infection_fatality_rate_of_SARS_CoV_2_infection2.pdf/%24FILE/Streeck_et_al_Infection_fatality_rate_of_SARS_CoV_2_infection2.pdf"]Abstract[/link]