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Summarized by Gudrun Westermann
From June 16 - 19, the KIT Congress took place as a purely virtual event. At the opening on the evening of the first day of the congress, RKI head Prof. Lothar Wieler emphasized that public health measures are the core of pandemic control. Many presentations at KIT also dealt with COVID-19, including historical pandemics, SARS-CoV-2 in children, and hygiene and testing concepts.
What can we learn from historical pandemics?
Against the background of the current COVID-19 pandemic, the question also arises as to what we can learn from historical pandemics. Prof. Johannes Krause from Leipzig reported on the results of his research group, which is studying the genetic history of the plague. The focus of research initially shifted away from infectious diseases in the 20th century in favour of lifestyle diseases such as diabetes and heart disease. Since the 1980s, however, there have been new waves of infectious diseases: HIV, Hanta, Ebola, SARS I, etc. Many infectious diseases started as zoonoses. Little is known about the early evolution of pathogens, especially for zoonoses. In the research project "Ancient Pathogen Genomics", the genomes of ancient pathogens are now being obtained and studied. DNA can be extracted from skeletons, for example. This can provide information about how pathogens have changed over the centuries and how they have adapted to the new host (humans).
There have been at least three major plague pandemics in Europe, and later in Asia, where plague still exists today and is very common in rodents. Samples from various sites across Europe show that these strains are all identical. Thus, in the 14th century, all plague victims died from a clone of the same bacterium within 5 years – there was apparently no change in the genome within that time.
Strains existing today in Africa and Asia all originated in Europe and arose by microevolution from the strain of that time. A new tool also allows new finds to be compared with a database, making it possible to process huge data sets even without a clue as to the cause of death. The research has also shown that plague has adapted to fleas as vectors over the millennia, and that the mutation rate of the pathogens is 10 times higher than previously thought. In general, the mobility of pathogens is always accelerated by humans (through migration, trade, conquest campaigns, ships, etc.). Here we find parallels to today's rapid spread of the Corona virus.
COVID-19 hygiene concepts
Dr. Janine Zweigner, Cologne, described the hygiene measures against COVID-19. Personal protective equipment, especially masks are in focus. The tightness of the mask is crucial for its effectiveness, especially for beard wearers. Wearing caps is not really necessary, she explained. There are still bottlenecks in some cases, for example with non-sterile protective gloves, she said.
At the University Hospital in Cologne, masks with and without splash protection were produced in-house, and these are now even CE-certified. Hand disinfectants were filled into existing bottles, because the lack of bottles was the main problem, since they are manufactured in China.
Zweigner stressed the importance of hand disinfection after removing gloves. A certain detectability of the virus on inanimate surfaces exists after all. Training in this context is essential and must be adapted depending on the occupational group.
Contact tracing is also an essential component. Zweigner presented the concept of Cologne University Hospital. Information and communication are the essential components: there is a newsletter, a hotline, information on the intranet, plus posters and flyers also for patients and visitors.
Prof. Eike Steinmann from Bochum spoke about possibilities to inactivate SARS-CoV-2. He described different types of viruses – enveloped and non-enveloped – and explained that SARS-CoV-2 viruses are relatively labile. Different components are destroyed to different degrees by heat. A review paper from early 2020 presented that SARS-CoV-2 viruses are sensitive to disinfectants and also to soap. WHO formulations based on ethanol and iso-propanol work very well, already proven against SARS and MERS, as well as against SARS-CoV-2 viruses.The same sensitivities apply to the new variants.
Steinmann then went on to discuss mouth rinses that may be able to help reduce viral loads. All mouth rinses showed some effect, some even complete inactivation. Clinical studies are still pending. Steinmann pointed out that infectivity is crucial, not just the PCR reaction – no great influence is to be expected on PCR results. Therefore, one must always also investigate the virus culture in order to evaluate the influence of mouth rinses on infectivity.
Finally, Steinmann mentioned a study on the stability and inactivation of corona viruses on banknotes and coins. Touch transfer studies with animal corona viruses, which are not infectious for humans, showed that after a short drying period there is practically no more transmissibility here. The virus is even more labile on coins (made of copper) than on banknotes.
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COVID-19 in children
Prof. Sandra Ciesek from Frankfurt reported on testing strategies at schools and kindergartens, especially the SAFE KIDS study (SARS-CoV-2 early detection). In this study, dual swabs were performed once a week.
However, with only this swab, many cases were missed. With an additional anal swab, detection was increased to almost 40%, compared to only 10% positives previously.
The first study was performed at quite a low incidence rate, so a second study with the same design followed during a high incidence phase. Clusters were not found here either, only single infectious children and breakthrough infections in educators not previously known. The SAFE Kids 3 study was conducted using the lollipop method, and results are expected in July.
In her conclusion, Ciesek said, "Infections in daycare centers are rare during low incidence phases. However, despite higher numbers of infections at higher incidences, no clusters were detected, so it appears daycare centers are not a reservoir for SARS-CoV-2, she said. Viral loads in school children are comparable, but they rarely become severely ill.
Teachers talk loudly and a lot, so aerosol formation plays a greater role here, and they teach multiple classes. The SAFE School study therefore focused on teachers who self-administered an antigen test every 2 days. Out of 4000 tests, 13 were positive but negative in the PCR follow-up test. After the fall break during a high incidence phase, 11 of 9000 were positive, 7 of which were confirmed by PCR. False positive tests resulted especially from S. aureus colonization, Ciesek explained. When incidence is high, antigen tests are useful to quickly detect clusters. In the meantime, they are also standard in schools for students.
Prof. Arne Simon from Homburg reported on a SARS-CoV-2 outbreak in a neonatology unit in South Africa. The index patient was a nurse. Problems here included the long latency from specimen collection to PCR test results, plus visits by mothers who went home again each day and then came back to the clinic, which encouraged the introduction of further infections.
Another study found risk factors for nosocomial transmission of SARS-CoV-2: Patient contact without adequate protective clothing and staff contact without distance and protective equipment in the community outside the hospital. Mildly or asymptomatically infected visitors may also transmit the virus. Measures are often not as observed for contacts between staff as they are for patient contact; transmission is possible here as well.
Simon went on to discuss the Infection Protection Act. It is discussed to use only vaccinated personnel in contact with vulnerable patients. According to §23a, the employer can also request information on vaccination protection and, if necessary, can no longer deploy employees in such areas. However, the de facto nursing shortage counteracts this.
Prof. Reinhard Berner, Dresden, spoke about SARS-CoV-2 in children. Overall, he said, SARS-CoV-2 cases requiring intensive care are rare, often affect children with preexisting conditions, and deaths are also rare. He presented the Pediatric Inflammatory Multisystem Syndrome (PIMS) registry. The incidence is approximately 1:5000 as a result of SARS-CoV-2 infection in children and follows COVID disease in a time interval of approximately 4 weeks. Therefore, an immunologic cause should be suspected. The PIMS course is usually more severe than in the similar Kawaski syndrome. In the registry so far 350 cases have been reported in Germany. Two thirds of the children are older than 7 years, with a clear clustering in boys. There is gastrointestinal involvement in 75% of patients, in addition to fever and cardiovascular symptoms. Residual symptoms, however, regress with time.
The older the children are, the higher the risk for a severe course.
In addition to high inflammatory parameters, hyponatremia is common, often leading to circulatory symptomatology. There are hypotheses about pathogenesis, such as an HLA dependency, but much remains to be learned here, Berner said.
Microbiome and COVID-19
PD Dr. Jan Kehrmann from Essen spoke about the importance of the gut microbiome. Severe courses of COVID-19 occur mainly in patients with underlying diseases in which the microbiome is also altered, for example in diabetics.
Studies of rectal swabs have also shown an inflammatory signature of the gut microbiome in SARS-CoV-2 positive patients, in terms of marked dysbiosis of the gut microbiome. The changes are not specific and are also found in other (viral) infections. For example, the gut microbiome is known to influence the severity of influenza infections of the lung.
Christoph Stein-Thöringer from the German Cancer Research Institute (DKFZ) in Heidelberg presented a study on the oropharyngeal microbiome. Despite increasing knowledge of the clinical and immunological features underlying COVID-19, biological variables that explain the course of infection and its severity remain elusive. However, at the entry site of SARS-CoV-2, the oropharyngeal microbiome likely plays a role.
In a multicenter clinical trial the oropharyngeal microbiome in healthy adults, patients with non-SARS-CoV-2 infection, or with mild, moderate, and severe COVID-19 disease was analyzed, which included a total of 345 participants.
Significantly reduced microbiome diversity and high dysbiosis were observed in severely ill hospitalized patients. This is exacerbated by administration of antibiotics. Ventilation also disrupts the microbiome.
Are there biomarkers that can predict outcome in COVID-19 patients? To find out, samples were taken from patients on the first three days after admission. This showed that species variability correlated quite well with outcome, better than clinical factors (e.g., obesity). High levels of Neisseria and Haemophilus spp. appear to be predictors of better survival. However, the pathophysiologic significance of these findings remains to be elucidated.
Travel in pandemic and post-pandemic times.
Dr. Sophie Schneitler, Saarland University Hospitals, spoke about testing for travellers. She presented the grouping of travellers by corona status and explained that convalescents are reclassified as unvaccinated/not previously ill after 6 months. When arriving from a virus variant area, everyone must be quarantined for 14 days regardless of classification.
Today, a pandemic can spread within a few days, especially through travel. Early detection is therefore important. But when does testing make sense? Schneitler reported on a case where infected persons were already symptomatic, but the PCR of the original carrier only became positive afterwards. Nevertheless, testing is definitely useful, and also represents an opportunity to detect other travel-associated diseases and hazards.
However, questions remain: What counts as travel? Is crossing the border the defining characteristic? Harmonization would make the process easier for everyone, Schneitler said. For example, decisions need to be made about how to handle patients who are still PCR-positive in the absence of infectivity; currently, if the positive test is older than 28 days, a certificate is usually issued that permits for example air travel.
Prof. Patricia Schlagenhauf from Zurich spoke about vaccinations. The COVID-19 vaccination can be confirmed in the yellow WHO vaccination certificate and then has international validity. The EU certificate has been available since mid-June.
However, vaccination should not be a prerequisite for travel, as otherwise travellers might be preferentially vaccinated and there could be a bottleneck for prioritized individuals. And what if there is no access to vaccination or someone cannot be vaccinated? Will travel become a privilege for rich countries?
Despite these issues, the certificates are a step forward and will make travel easier, especially for those at low risk, and economic and tourism factors will be positively impacted, Schlagenhauf said.
The variants present a new challenge for vaccination, and the duration of vaccine protection is a factor. Currently, efficacy is assumed for a duration of 12 months. 8 days after a COVID vaccination, other vaccinations are possible, she said. The other way around, however, the interval should be longer, since no experience is available yet.
What role do models play?
Prof. André Karch from Münster posed the question of what role mathematical models play in the pandemic and emphasized that mathematical models basically cannot and do not want to be prognosis models. The goal of modelling, he said, is primarily to depict realistic scenarios, and it is important to remember that the results of modelling themselves will change the future if they are taken seriously and trigger appropriate reactions or changes in behaviour.
Last year was the first time that models and modelers received public attention and not only positive reactions, in part because the models appeared to have an impact on pandemic management.
Karch presented study documents that may have played a role at the beginning of the first wave: Report 9, which, in addition to an expected high death toll, presented the fact that individual classical infection prevention measures alone would not have a significant impact on the course in each case.
Karch emphasized that modelers are in a very critical situation, especially with new diseases. They are expected to make predictions based on very little information, which may then be used to make decisions in a charged situation. In the pandemic, decisions must initially be made with little evidence; over time, the evidence improves, but the questions also become more complex.
The crucial part of any modelling study is finding the appropriate parameters; this takes up the bulk of the work, Karch said, illustrating this with the contact structure in the population. Not only does the number of contacts play a role, but the particular setting in which people meet is also crucial. The data from the first wave can be reconciled very well with so-called small-world networks, i.e., people have contact with each other in certain groups, and individuals from each group also have contact with people from another small network. With respect to contact tracing, modelling shows that minimizing the delay in isolation has the best effect.
Regarding herd immunity, Karch explained that the simple assumption that 2/3 immunes in the population were sufficient was not so. Fewer people would then become infected, but there will still be infections until about 90% are infected or immune. He illustrated this course with measles: Since the availability of vaccination, the epidemics have decreased significantly, but continue to occur again and again, because there are always new susceptible people and, on the other hand, immune people die, so that the threshold for herd immunity can be undercut again and again (possibly only locally).
Models were initially used, for example, in the question of how best to prioritize vaccination; the decision to make a distinction between those over 80 and those over 60 was based on this, for example. Similarly, it can be shown in the models that the effect of vaccinating children and adolescents would be marginal both on deaths in this group and on overall infection dynamics.
Finally, Karch explained that current events, such as the images from Bergamo at the beginning of the pandemic, have a stronger influence on decisions than possible results from modelers.
COVID – how is it going elsewhere?
Hojoon Sohn of Johns Hopkins University reported on the handling of COVID-19 in South Korea. He showed that waves of infection have been significantly contained by spacing and masks, and especially with the start of the vaccination campaign, numbers have dropped significantly. He also showed that the reopening of schools has led to a slight, but not significant, increase in infection numbers. There is still a great deal of testing going on.
Sohn summarized the learning points from the 2015 MERS epidemic. Delayed identification of cases, as well as lack of structures for communication and lack of training for medical staff on how to deal with this novel infection, led to numerous outbreaks.
Much has changed since then, as Sohn explained, based on the current structures of the South Korean healthcare system. Among other things, a national laboratory system has been established that allows rapid diagnosis everywhere. There are also free testing facilities, and epidemiological investigations and contact management have been massively expanded. Among other things, for confirmed cases, the contact and movement data of these patients are matched using, among other things, mobile phone data, credit card transactions or use of public transport. However, this has also led to privacy issues. With regard to travellers, quarantine measures are very effective. For example, there are special carriages on trains and specially equipped taxis for passengers arriving internationally.
Prof. Ayola Akim Adegnika, University of Tübingen, reported on the measures in Gabon. He explained that in many places in Africa, there is insufficient testing infrastructure, which can lead to relatively low reported case numbers. Since the first cases appeared in Gabon in March 2020, schools have been closed, currently there is also still a night curfew, and the well-known measures play an important role: masks, testing, social distancing, and contact tracing. The laboratory structure has been significantly expanded so that patients with fever or other symptoms, as well as travellers, can be tested free of charge. What about treatment? Intensive care units exist only in the provincial capitals. The majority of cases are asymptomatic or mild, and mortality is low. However, not all cases of illness and death are likely to be reported either. The vaccination campaign with the Chinese vaccine Sinopharm started in March 2021 and will be carried out at more than 20 vaccination centres in the country. Anyone over 18 can be vaccinated. However, there is a great deal of vaccination scepticism in the country. Negative reports spread quickly throughout the country via social media. Variants of SARS-CoV-2 are also spreading in the country. Therefore, there are also restrictions and quarantine and testing obligations for travellers.
Yannik Eggers from Düsseldorf reported on activities of the Hirsch Tropical Medicine Institute in Ethiopia, which is an outpost of Heinrich Heine University. The city of Asella in the Aris region has about 4 million inhabitants. The first case in Ethiopia was identified in March 2020. Since then, laboratory capacity has been expanded, primarily at the regional level.
Eggers reported on activities on the ground in Asella and at the institute, including training, laboratory expansion and testing.
Especially at the beginning of the pandemic, COVID-19 had a strong impact locally, e.g., supply shortages, unclear management of emergency patients, and stigma and discrimination also played a major role.
The majority of patients treated in the hospital have no preexisting conditions. Approximately 60% of patients receiving intensive care died. Many patients with minor symptoms were also admitted, especially in the beginning, mainly to isolate them from their environment.
In the meantime, a lot of practical experience has been gained, the implementation of hygiene measures has improved significantly and has become commonplace, and the capacities for PCR testing and the digital infrastructure have been expanded.
Moreover, various studies have been initiated, such as the introduction of an app for contact tracing and the COVSERO study on seroprevalence.
