Prof. Dr. Christian Drosten - Berlin site manager of the National Research Platform for Zoonoses - includes in his considerations in his much-received podcast on NDR a large number of studies that are currently published on pre-print servers. As a special service we have linked the studies to the individual episodes below.
Sources:
Christophe Fraser/ Feretti et al.
https://science.sciencemag.org/content/early/2020/03/30/science.abb6936
Calculation of the proportion of pre-sympathetic, sympathetic and asympathetic transmissions, etc.
Efficiency of different measures, hypothetical app with contact tracing and information to persons who were in the vicinity
→ Even if isolation is carried out immediately at the onset of symptoms, there are already infected persons from the isolated person as well as from those infected
Transmission via surfaces evaluated as a maximum of 10% (mentioned in episode 28)
Chen et al. (Chinese Chloroquine Study)
https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2
Small randomized study groups, but small, significant improvement effect visible, comparability of both test groups not fully clarified
Link to the episode (German)
Sources:
Measures that are recommended by "Leopoldina"
https://www.leopoldina.org/uploads/tx_leopublication/2020_04_03_Leopoldina_Stellungnahme_Gesundheitsrelevante_Ma%C3%9Fnahmen_Corona.pdf
→ With masks and voluntary apps until mid-May below 1.0 newly infected persons per infected person possible
Mask study from Hong Kong (pre sars-cov2)
https://www.nature.com/articles/s41591-020-0843-2
→ 11 Coronavirus-infected persons with mask, after 30 minutes no virus found in the room air, in 10 infected persons without mask already
Publication on stability of sars-cov2 (New England Journal)
https://www.nejm.org/doi/full/10.1056/NEJMc2004973
In aerosol, virus is still infectious for 3 hours (but only under laboratory conditions with high virus concentration)
Study from Singapore, indoor air analysed over several days
https://www.medrxiv.org/content/10.1101/2020.03.29.20046557v2
SARS-CoV2 patients, One patient (day 9) with little virus in airways → in ambient air nothing detectable; 2 patients with much virus in airways, to both droplet sizes in ambient air virus RNA detectable. (→ Transmitted by breathing in ambient air possible)
Wipe samples were also taken from surfaces in 30 hospitals. Only in first week of symptoms
positive wipe samples! → The later in the disease the less infectious.
Study from Iran: loss of taste and smell described
https://www.medrxiv.org/content/10.1101/2020.03.23.20041889v1
Symptom more frequently described in a family of sufferers of olfactory system failure than respiratory problems
Mentioned in the note:
Belgian study on the same phenomenon
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134551/
Sources:
Dutch study "Virus in wastewater as an indicator"
https://www.medrxiv.org/content/10.1101/2020.03.29.20045880v1
SARS-cov2 RNA detectable in wastewater (This does NOT mean that this wastewater is infectious)
also: "Munich Study" by Charité Berlin
https://www.nature.com/articles/s41586-020-2196-x
No infectious virus detectable from stool RNA
Link to the episode (German)
Sources:
Corona data donation Link
https://corona-datenspende.de/
Epidemiological modelling of the spread of influenza-like diseases, Radin et al (USA)
https://www.thelancet.com/journals/landig/article/PIIS2589-7500(19)30222-5/full text
Link to the episode (German)
Quellen:
"Munich Study" (already mentioned in episode 29)
https://www.nature.com/articles/s41586-020-2196-x_reference.pdf
Excretion over time in 9 patients (detection limit of PCR visible)
-> statistical distribution phenomena, as virus is present but not always detectable
(Explanation for alleged reinfections in discharged patients in South Korea)
Reference to:
First study from Wuhan (5/55 recovered patients tested positive again)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102560/
Unsicherheit über die Abstrichmethode (einige Arten von Proben sind signifikant länger positiv als andere)
Zweite Studie aus Wuhan (25/172 genesene Patienten wieder positiv getestet)
https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa398/5817588
Im Mittel 5,23 Tage nach Entlassung wieder positiv getestet,
Entlassungskriterium waren 2 negative Rachenabstriche (dieser Probentyp ist sehr früh negativ) hintereinander
Link to the episode (German)
Sources:
Epidemiological study on Italian village
https://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1
Almost all inhabitants of the small village were tested twice and asked about symptoms.
-> 43.2% asymptomatic Covid19 cases. However, just as high virus excretion!
Californian antibody study with ELISA rapid test
https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1
1.5% of those tested; after calculation on age groups 2.8% of the population with antibodies;
of positive controls (known infected) only 70% detected.
-> Population prevalence in the lower single-digit percentage range, thus still far from herd immunity
Icelandic study, from which it was concluded that children under 10 years of age would not be infected
https://www.nejm.org/doi/full/10.1056/NEJMoa2006100?query=featured_coronavirus
Test subjects were once returnees from risk areas and their contact persons,
once volunteers (without too strong symptoms), therefore rather no asymptomatic cases,
as they often seem to be with children -> significance difficult to judge
Study from Shenzen
https://www.medrxiv.org/content/10.1101/2020.03.03.20028423v3
Cohort study with 1286 contacts of 400 infected persons.
Attack rate (rate of contacts of infected persons who also became infected) the same
between different age groups from 0-9, 10-19 and 20-30 years.
However, only one study, no data on virus excretion between children and adults
Study from Hong Kong by Gabriel Leung
https://www.nature.com/articles/s41591-020-0869-5
"44% of transmission before symptoms begin"
Most infectious day the day before the onset of symptoms, after 4 days usually hardly infectious, after one week not at all
Sources:
English Office for Statistics on Mortality during Corona
https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsregisteredweeklyinenglandandwalesprovisional/weekending10april2020
New York Times, charts of mortality curves from different countries
https://www.nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html
Significant increase up to doubling of the mortality rate in various countries, despite measures in these countries
Many countries with a 'missed' month, because they only reacted to rising death rates. Germany with a lead
Modelling study from France
https://hal-pasteur.archives-ouvertes.fr/pasteur-02548181/document
Even after a long lockdown from epicenters of the epidemic, little has been achieved,
2.6% of infected persons have to go to hospital, infectious mortality rate modelled at 0.53%,
8.3 % for over 80-year-olds (retirement homes omitted)
Link to the episode (German)
Sources:
Statement by Ranga Yogeshwar on the question whether the "lockdown" was for nothing (German)
https://www.youtube.com/watch?v=OLBav50d-X8&feature=youtu.be
When viewing the reproduction figure curve of the RKI, prior soft measures and
the change in test capacities can be included. The effect of the lockdown at the beginning of April is also
can be recognized by a bend in the curve.
Vaccination study on rhesus monkeys from Beijing
https://www.biorxiv.org/content/10.1101/2020.04.17.046375v1.full.pdf
Eight rhesus monkeys vaccinated (dead vaccine) and infected.
Vaccinated animals without lung damage, almost no virus replication to be found.
Furthermore no side effects like a boosted immune reaction.
Study on T-helper cells, by Charité Berlin
https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1
Indications of T cell immunity after coronavirus-induced cold.
However: Not necessarily 30% of Germans are immune, even negative effects are conceivable,
or explanation for many asymptomatic to mild cases
Link to the episode (German)
Sources:
Household contact study from Wuhan
https://www.nature.com/articles/s41586-020-2271-3
Children without symptoms, but 15% of children in households with first-time infections infected in the observation period
i.e. just as frequently as all other age groups
Study from the Netherlands
https://www.rivm.nl/coronavirus-covid-19/kinderen
Broken down by contact person, children had much less contact with infected persons, but not significant, as only a few children were included in the study
Basic study on autophagy from Bonn
https://www.biorxiv.org/content/10.1101/2020.04.15.997254v1.full.pdf
Like the MERS virus, SARS-Cov2 interferes with autophagy via the Beclin-2 network,
Autophagy supporting pharmaceuticals like niclosamide, MK-2206, spermidine could help.
→ Permitted concentration of niclosamide prevents virus in vitro, therefor currently applying for clinical trials on infected persons
Link to the episode (German)
Sources:
Analysis of viral load by age of patients at Charité Berlin
https://virologie-ccm.charite.de/fileadmin/user_upload/microsites/m_cc05/virologie-ccm/dateien_upload/Weitere_Dateien/analysis-of-SARS-CoV-2-viral-load-by-patient-age-v2.pdf
Children not with lower virus concentration in respiratory tract than adults; the (few) symptomatic children rather with lower virus concentration (!)
The Lancet study: Contacts in households
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30357-1/full text
Children and adults with an infection rate of approximately 12%.
Science study from Shanghai on the risk of infection for children
https://science.sciencemag.org/content/early/2020/04/28/science.abb8001?rss=1
6.2 % of children (0-15), 8.6 % of adults in index patient infected, but with included probability of contact, children have only one third of the risk of infection
Link to the episode (German)
Sources:
"Heinsberg Study" from Gangelt by Dr. Streeck (Bonn)
https://www.uni-bonn.de/news/111-2020?set_language=en
High number of unreported cases; projected 1.8 million infections in Germany (10 times as high as the official figure), -> Still a long way to herd immunity;
Infection mortality rate of 0.36% (confirmed antibody tests were not included in this calculation)
Study on high school in Oise (Northern France)
https://www.medrxiv.org/content/10.1101/2020.04.18.20071134v1.full.pdf
5 weeks of unnoticed outbreak in school, 38.3% students, 43.4% teachers, 60% other employees infected
but possibly not representative (voluntary nature of the study with mutual effects)
Study on the risk of infection for smokers
https://www.qeios.com/read/WPP19W.3
Only "strikingly" low proportion of smokers among infected persons in French university hospital -> Does not mean that courses are also easier
No explanation provided, must first stand up to scrutiny (Dr. Drosten is not convinced yet)
Data from 15 schools in Australia
http://ncirs.org.au/covid-19-in-schools
Only low attack rates of students, study not yet completed, no scientific publication (not even preprint),
nevertheless already translated into political decisions
Geneva study by Isabella Eckerle
https://www.medrxiv.org/content/10.1101/2020.04.27.20076778v1
23 children's cases (between 0 and 16 years) from hospitals and sending practices were examined,
on average considerable virus concentration with infectious virus, in younger children perhaps lower
-> No statistical reason to assume that virus concentration in children is different from that in adults
Link to the episode (German)
Sources:
Study on antigen test
https://www.medrxiv.org/content/10.1101/2020.04.24.20077776v1.full.pdf
"Pregnancy test for sars-cov2" with monoclonal antibodies of the sars virus' from 2003,
75% of highly infectious patients detectable, low infectious patients poorly detectable
-> helpful for first decision making in emergency rooms etc
Study from Toronto on the significance of saliva tests
https://www.medrxiv.org/content/10.1101/2020.05.01.20081026v1.full.pdf
Thai study on the same question
https://www.medrxiv.org/content/10.1101/2020.04.17.20070045v1
US study
https://www.medrxiv.org/content/10.1101/2020.04.16.20067835v1
-> Saliva samples in comparison to other respiratory diseases Saliva samples in
Covid19 very sensitive; slightly less accurate (in Thai study compared to double smear) to better (US study) than smear
Less prone to sampling errors
Link to the episode (German)
Sources:
Chinese study (mentioned)
https://wwwnc.cdc.gov/eid/article/26/7/20-0764_article
Aerosol transmission component quite a factor, shown in restaurant in Guangzhou
Modelling study by Columbia University
https://www.mailman.columbia.edu/public-health-now/news/projections-suggest-potential-late-may-covid-19-rebound
Two different models for possible second wave in May
Study from France
https://www.sciencedirect.com/science/article/pii/S0924857920301643
Sample of a pneumonia patient from December 2019 tested positive for SARS-COV2 by PCR,
but without further testing and sequencing of the virus, obviously too much positive control -> cross-contamination?
Chinese study on SARS-like viruses in bats
https://www.biorxiv.org/content/10.1101/2020.03.02.974139v3.full.pdf
cleavage site in the spike protein as well as in SARS-COV2
Study from Los Alamos
https://www.biorxiv.org/content/10.1101/2020.04.29.069054v2.full.pdf
Hypotheses on changes in infectiousness based on molecular changes in the spike protein,
Wuhan virus without mutation seems to be harmless compared to the virus that came into the world from Shanghai,
but possibly only by chance, as no clear difference in fitness has been shown so far
Link to the episode (German)
Sources:
Economic study
https://www.ifo.de/DocDL/sd-2020-digital-06-ifo-helmholtz-wirtschaft-gesundheit-corona_1.pdf
Dance with the tiger, slow, assured loosening most effective, because quarantine measures
may be more economically harmful than light restrictions; R=0.75 optimal for economy
and also good for health
Hamburg study
https://www.nejm.org/doi/full/10.1056/NEJMc2011400
virus replicates in various organs, including kidneys and damages them
Studies on Kawasaki syndrome-like clinical picture
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31103-X/full text
Vascular inflammation apparently caused by SARS-COV2, also observed in children,
fortunately rare and treatable
Link to the episode (German)
Sources:
Epidemiological study from Italy
https://www.bmj.com/content/369/bmj.m1835
excess mortality in Italy much higher than the officially reported Corona deaths
in a small Italian town of 11,500 inhabitants with a mortality rate 15 times higher than normal
NYT report on Covid19 outbreak in Nigerian town of Kano
https://www.nytimes.com/2020/05/17/world/africa/coronavirus-kano-nigeria-hotspot.html
Relatively small number of cases documented, but a large number of infected persons among tested doctors
Study on the mortality risk of swine flu
https://journals.lww.com/epidem/fulltext/2013/11000/Case_Fatality_Risk_of_Influenza_A__H1N1pdm09___A.6.aspx
As many deaths as during normal flu waves, but a great many middle-aged adults were affected by swine flu
affected, -> cross-immunity of old people by H1N1 virus of the Spanish flu and subsequent years -> was unexpected
Link to the episode (German)
Sources:
Statement of the German Society for Pediatric Infectiology
https://dgpi.de/stellungnahme-schulen-und-kitas-sollen-wieder-geoeffnet-werden/
Claim: "Children play a subordinate role in the spread of SARS-CoV2",
However, the introduction of the virus by children into the family should not be investigated;
nevertheless important contribution to the discussion
Japanese Study
https://www.medrxiv.org/content/10.1101/2020.02.28.20029272v2
19 times the risk of being infected indoors compared to outdoors
Chinese study on household outbreaks
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281
108 out of 318 outbreaks associated with public transport, only 14 with restaurant visits
Another Chinese study on attack rate by age group
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281
U18-year-olds only infected by index patients in 4% of households, but 17.1% of adults,
but which, under Chinese quarantine conditions.
Study from Geneva in Switzerland on attack rate
https://www.medrxiv.org/content/10.1101/2020.05.02.20088898v1
5-19-year-olds and 20-49-year-olds here without major differences (no other age groups examined)
Swedish study
https://www.folkhalsomyndigheten.se/the-public-health-agency-of-sweden/
Random samples tested with PCR, no significant differences of
Distribution of infected persons between children and adults
Link to the episode (German)
Sources:
Study on stochastics
https://covid.idmod.org/data/Stochasticity_heterogeneity_transmission_dynamics_SARS-CoV-2.pdf
Research group names 4 categories of superspreading events: opportunities (choir, cruise, etc.), permanent venues (such as accommodation),
social behaviour and unknown biological factors
Review in "Science" by Kai Kupferschmidt
https://www.sciencemag.org/news/2020/05/why-do-some-covid-19-patients-infect-many-others-whereas-most-don-t-spread-virus-all
"Nature" study by Lloyd Smith
https://www.nature.com/articles/nature04153
Prevent social situations that encourage many infections:
At a control power of 30% (assuming masks are that effective), which is only half as effective in 20% of the most infectious persons
"arrives", an epidemic of the magnitude SARS-1 (dispersion factor 0.1) must be stopped.
Swiss study from January
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.4.2000058
Dispersion factor estimated at 0,3 to 0,6
London study
https://wellcomeopenresearch.org/articles/5-67
Assume 10% "superspreaders"; estimate dispersion factor 0.1 to 0.3,
Data basis (from countries other than China) uncertain
Hong Kong Study by Gabriel Leung
https://www.researchsquare.com/article/rs-29548/v1
Cluster with minimum size in Hong Kong studied, dispersion factor of 0.45,
Even with early isolation several people are already infected -> Isolation in
Cluster candidates must be done before diagnostics!
Link to the episode (German)
Sources:
Study on effect of measures from "The Lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31142-9/full text
Investigation of Remdesivir as a drug against Covid19
https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
Used in patients with severe course, but little effect
-> Works against virus, but not against inflammation
Link to the episode (German)
Sources:
Virus load of the Charité (updated study)
https://virologie-ccm.charite.de/fileadmin/user_upload/microsites/m_cc05/virologie-ccm/dateien_upload/Weitere_Dateien/Charite_SARS-CoV-2_viral_load_2020-06-02.pdf
More precise statistical methods used; distinction between the origin of the samples (for example, outpatient clinic or intensive care unit);
intensive care patients often already in the second week of illness and thus hardly any virus in throat swabs;
At least 30% of children with a high viral load; no difference in the mean value according to age
Study by Viola Priesemann in "Science
https://science.sciencemag.org/content/early/2020/05/14/science.abb9789
Model calculation for effect of measures in Germany; ban on major events reduced propagation rate from 0.43 to 0.25;
school closures then down to 0.15; after general contact limitation down to 0.09
Preprint from Oxford
https://www.medrxiv.org/content/10.1101/2020.05.28.20116129v2.article-info
Effects of nine different measures examined; data from 41 countries;
school closures in the period of expansion strongest effect in this model (50% reduction)
Link to the episode (German)
Sources:
Localization of infected tissue types with GFP
https://www.cell.com/cell/pdf/S0092-8674(20)30675-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306759%3Fshowwall%3Dtruehttps://www.biorxiv.org/content/10.1101/2020.05.28.118992v2
Green fluorescent protein incorporated into virus to mark infected cells in tissues;
SARS-Cov2 particularly often found in nasal mucosa epithelium
Link to the episode (German)
Sources:
Study on susceptibility of different blood groups
https://www.medrxiv.org/content/10.1101/2020.05.31.20114991v1
Higher risk of a severe course with blood group A,
little heavy with blood group 0
New antibody study from Zurich
https://www.biorxiv.org/content/10.1101/2020.05.21.108308v1.full.pdf
IgA antibodies in addition to IgG antibodies;
Symptomless positives without IgG, but already with IgA antibodies;
-> apparently local IgA infection
Study on the effect of the prevented effects
https://www.nature.com/articles/s41586-020-2405-7
Germany with only 0.85 % infected compared to England, Italy, France and Spain with several percent,
several hundred thousand deaths acceptable without any measures at all
Study from California by economists
https://www.nature.com/articles/s41586-020-2404-8
Without measures, a daily growth rate of up to 38% could have been possible (based on rough estimates)
Study on compulsory masks in Jena
https://download.uni-mainz.de/presse/03_wiwi_corona_masken_paper_zusammenfassung.pdf
Comparison of a hypothetical maskless Jena with the actual Jena; 23% less increase of infections;
Apparently, "announcement effect" also visible;
in addition, a comparison of districts: districts with compulsory masks 40% less increase per day compared to comparable districts without compulsory masks
