ABSTRACT
There is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 months of the pandemic in the community had a positive test for SARS-CoV-2. Six out of 18 SARS-CoV-2+ deaths had non-COVID-19 related causes of death (COD). Individuals with confirmed infection and COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p=0.029). Duration between first confirmed infection and death was negatively associated to COVID-19 being COD (p=0.04). Repeated seroprevalence essays on an original sample of 587 individuals in three visits showed modest increases in seroprevalence over time, and substantial seroreversion (30% [27/90] (95% CI: [20.5%; 39.5%])). IFR estimates accordingly varied depending on COVID-19 death attribution and seroprevalence caveats. Careful ascertainment and audit of COVID-19 deaths are important in understanding the impact of the pandemic.
ABSTRACT
BackgroundThe beginning of the COVID-19 pandemic was shaped by superspreading events including large-scale outbreaks. In Germany the first SARS-CoV-2 outbreak was a superspreading event in a rural area during indoor carnival festivities in February 2020. Methods51 days after the event all known participants were asked to give blood samples, pharyngeal swabs and answer a self-administered questionnaire. Metric room coordinates for all tables, seats, and ventilation-points were assessed. FindingsWe analyzed infection rates among all 411 participants, and the risk of infection in relation to various factors including age, alcohol consumption, and ventilation system. Overall, 46% (n=186/404) of the participants had been infected. We demonstrate that the spatial distribution of infected participants was associated with proximity to the ventilation system (represented as inverse distance, with Odds Ratio OR 1.39, 95% KI [0.86; 2.25]). Interestingly, the risk of infection was highly associated with age, whereby children (OR: 0.33 [0.267; 0.414]) and young adults (age 18-25) had a lower risk of infection than older participants resulting in an average infection risk increase of 28% per 10 years age difference. Behavioral differences also impacted the risk of infection including time spent outside (OR: 0.55 [0.33; 0.91]) or smoking (OR: 0.32 [0.124; 0.81]). InterpretationOur findings underline the importance of proper indoor ventilation for events in the future. The lower susceptibility for children and young adults indicates their limited involvement in superspreading events. FundingThe government of North Rhine-Westphalia (Germany) supported the study with 65,000 Euro. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe scientific literature was searched for the term "superspreading event AND Covid-19 OR Sars Cov 2" and identified published papers from China, South Korea, Europe, and North America. Most researchers analyzed superspreading events within a health care setting e.g. in hospitals or nursing homes, or described the general impact of superspreading events on the global pandemic. Only a few metanalyses of transmission clusters analyzed party occasions (e.g. a nightclub in Berlin, Germany) as superspreading events. These reports describe less than 100 infections and are very limited due to missing data or reporting biases. Therefore, the ability to draw scientific conclusions is also limited. Additionally, to our knowledge, there are no studies, which investigated individual behavior, the location, and role of children during a superspreading event. The research for the study started April 2020 and was concluded in June 2021. Added value of this studyOur report analyzes the first COVID-19 superspreading event in Germany in detail, which was not only a unique setting but also included children and adults in the same room. We demonstrate that nearly half of the participants were infected with SARS-CoV-2 and that the proximity of the seating to the ventilation system was an important risk factor for infection. The data showed that low physical distance including singing and duration of attendance at this event increased the risk of infection, while regular smoking and spending the break of the event outside lowered the risk of infection. This underlines the benefit of airing to lower the amount of both droplets and aerosols. Furthermore, we found lower infection in children than adults despite being in the same room suggesting differences in infectability in children. Indeed, we observed that an additional 10 years of age is on average associated with 28% increased risk of infection. Implications of all the available evidenceTaken together, the results demonstrate the importance of the ventilation system during superspreading events. In particular children and young adults had a lower risk of infection during the event indicating that they have a limited role during this pandemic. Overall, our data demonstrate in detail age-dependent infectability as well as highlights to understand transmission dynamics in order to improve comprehensive public health preparedness measures.
ABSTRACT
BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2. ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12{middle dot}4 % in week six, p<0.001). In sera of convalescent PCR-confirmed COVID-19 patients, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from ELISAs using e.g. the S1 spike protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralization. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the six week study period. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralization against live SARS CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%. ConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. Here, we report that low plasma interleukin-3 (IL-3) levels were associated with increased severity and mortality during SARS-CoV-2 infections. IL-3 promoted the recruitment of antiviral circulating plasmacytoid dendritic cells (pDCs) into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells. This study identifies IL-3 as a predictive disease marker and potential therapeutic target for SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.View Full Text
ABSTRACT
The role of environmental transmission of SARS-CoV-2 remains unclear. Particularly the close contact of persons living together or cohabitating in domestic quarantine could result in high risk for exposure to the virus within the households. Therefore, the aim of this study was to investigate the whereabouts of the virus and whether useful precautions to prevent the dissemination can be given. 21 households under quarantine conditions were randomly selected for this study. All persons living in each household were recorded in terms of age, sex and time of household quarantine. Throat swabs for analysis were obtained from all adult individuals and most of the children. Air, wastewater samples and surface swabs (commodities) were obtained and analysed by RT- PCR. Positive swabs were cultivated to analyse for viral infectivity. 26 of all 43 tested adults (60.47 %) tested positive by RT-PCR. All 15 air samples were PCR- negative. 10 of 66 wastewater samples were positive for SARS-CoV-2 (15.15 %) as well as 4 of 119 object samples (3.36 %). No statistically significant correlation between PCR-positive environmental samples and the extent of infection spread inside the household could be observed. No infectious virus could be isolated under cell culture conditions. As we cannot rule out transmission through surfaces, hygienic behavioural measures are important in the households of SARS-CoV-2 infected individuals to avoid potential transmission through surfaces. The role of the domestic environment, in particular the wastewater load in washbasins and showers, in the transmission of SARS CoV-2 should be further clarified. HighlightsO_LIWith public "shut downs" due to SARS-CoV-2, domestic infection is a main possible route of transmission. C_LIO_LIAll analysed air samples were tested negative for SARS-CoV-2. C_LIO_LI15.15 % of all wastewater samples (washbasin, showers and toilets) were tested positive. C_LIO_LIOnly 3.36 % of all object samples were tested positive: one remote control, two metallic door knobs and one wooden stove overlay. C_LIO_LIThis study supports the hypothesis that indirect environmental transmission may only play a minor role, which needs clarifications in further studies. C_LI
ABSTRACT
We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.
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. MethodsA 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. ResultsOf 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<0.001) and the number of symptoms in the infected (estimated relative mean increase 1.6, 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). ConclusionsWhile 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.
ABSTRACT
We report a laboratory-based surveillance for SARS-CoV-2 using minipools of respiratory samples submitted for routine diagnostics. We tested a total of 70 minipools resembling 700 samples shortly before the upsurge of cases in Germany. We identified one SARS-CoV-2 positive patient. Our approach proved its concept, is easily adaptable and resource-saving.
