Socioeconomic and risk-related drivers of compliance with measures to prevent SARS-CoV-2 infection: evidence from the Munich-based KoCo19 study.

OBJECTIVES: Although a growing share of the population in many countries has been vaccinated against the SARS-CoV-2 virus to different degrees, social distancing and hygienic non-pharmaceutical interventions still play a substantial role in containing the pandemic. The goal of this study was to investigate which factors are correlated with a higher compliance with these regulations in the context of a cohort study in the city of Munich, southern Germany, during the summer of 2020, i.e. after the first lockdown phase. METHODS: Using self-reported compliance with six regulations and personal hygiene rules (washing hands, avoiding touching face, wearing a mask, keeping distance, avoiding social gatherings, avoiding public spaces) we extracted two compliance factor scores, namely compliance with personal hygiene measures and compliance with social distancing regulations. Using linear and logistic regressions, we estimated the correlation of several socio-demographic and risk perception variables with both compliance scores. RESULTS: Risk aversion proved to be a consistent and significant driver of compliance across all compliance behaviors. Furthermore, being female, being retired and having a migration background were positively associated with compliance with personal hygiene regulations, whereas older age was related with a higher compliance with social distancing regulations. Generally, socioeconomic characteristics were not related with compliance, except for education, which was negatively related with compliance with personal hygiene measures. CONCLUSIONS: Our results suggest that for a targeted approach to improve compliance with measures to prevent SARS-CoV-2 infection, special attention should be given to younger, male and risk-prone individuals.

Integrative modelling of reported case numbers and seroprevalence reveals time-dependent test efficiency and infectious contacts.

Mathematical models have been widely used during the ongoing SARS-CoV-2 pandemic for data interpretation, forecasting, and policy making. However, most models are based on officially reported case numbers, which depend on test availability and test strategies. The time dependence of these factors renders interpretation difficult and might even result in estimation biases. Here, we present a computational modelling framework that allows for the integration of reported case numbers with seroprevalence estimates obtained from representative population cohorts. To account for the time dependence of infection and testing rates, we embed flexible splines in an epidemiological model. The parameters of these splines are estimated, along with the other parameters, from the available data using a Bayesian approach. The application of this approach to the official case numbers reported for Munich (Germany) and the seroprevalence reported by the prospective COVID-19 Cohort Munich (KoCo19) provides first estimates for the time dependence of the under-reporting factor. Furthermore, we estimate how the effectiveness of non-pharmaceutical interventions and of the testing strategy evolves over time. Overall, our results show that the integration of temporally highly resolved and representative data is beneficial for accurate epidemiological analyses.

The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 - Results from a prospective cohort of outpatient COVID-19 cases.

Risk factors for disease progression and severity of SARS-CoV-2 infections require an understanding of acute and long-term virological and immunological dynamics. Fifty-one RT-PCR positive COVID-19 outpatients were recruited between May and December 2020 in Munich, Germany, and followed up at multiple defined timepoints for up to one year. RT-PCR and viral culture were performed and seroresponses measured. Participants were classified applying the WHO clinical progression scale. Short symptom to test time (median 5.0 days; p = 0.0016) and high viral loads (VL; median maximum VL: 3∙108 copies/mL; p = 0.0015) were indicative for viral culture positivity. Participants with WHO grade 3 at baseline had significantly higher VLs compared to those with WHO 1 and 2 (p = 0.01). VLs dropped fast within 1 week of symptom onset. Maximum VLs were positively correlated with the magnitude of Ro-N-Ig seroresponse (p = 0.022). Our results describe the dynamics of VLs and antibodies to SARS-CoV-2 in mild to moderate cases that can support public health measures during the ongoing global pandemic.

Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2.

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Spatially resolved qualified sewage spot sampling to track SARS-CoV-2 dynamics in Munich - One year of experience.

Wastewater-based epidemiology (WBE) is a tool now increasingly proposed to monitor the SARS-CoV-2 burden in populations without the need for individual mass testing. It is especially interesting in metropolitan areas where spread can be very fast, and proper sewage systems are available for sampling with short flow times and thus little decay of the virus. We started in March 2020 to set up a once-a-week qualified spot sampling protocol in six different locations in Munich carefully chosen to contain primarily wastewater of permanent residential areas, rather than industry or hospitals. We used RT-PCR and sequencing to track the spread of SARS-CoV-2 in the Munich population with temporo-spatial resolution. The study became fully operational in mid-April 2020 and has been tracking SARS-CoV-2 RNA load weekly for one year. Sequencing of the isolated viral RNA was performed to obtain information about the presence and abundance of variants of concern in the Munich area over time. We demonstrate that the evolution of SARS-CoV-2 RNA loads (between <7.5 and 3874/ml) in these different areas within Munich correlates well with official seven day incidence notification data (between 0.0 and 327 per 100,000) obtained from the authorities within the respective region. Wastewater viral loads predicted the dynamic of SARS-CoV-2 local incidence about 3 weeks in advance of data based on respiratory swab analyses. Aligning with multiple different point-mutations characteristic for certain variants of concern, we could demonstrate the gradual increase of variant of concern B.1.1.7 in the Munich population beginning in January 2021, weeks before it became apparent in sequencing results of swabs samples taken from patients living in Munich. Overall, the study highlights the potential of WBE to monitor the SARS-CoV-2 pandemic, including the introduction of variants of concern in a local population.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich.

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.

Adaptation of an international virtual patient collection to the COVID-19 pandemic.

The COVID-19 pandemic posed new global challenges for teaching. We met these challenges as an international collaboration by adapting a collection of virtual patients for clinical reasoning training to this novel context.

Publisher Correction to: Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19).

An amendment to this paper has been published and can be accessed via the original article.

Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19).

BACKGROUND: Due to the SARS-CoV-2 pandemic, public health interventions have been introduced globally in order to prevent the spread of the virus and avoid the overload of health care systems, especially for the most severely affected patients. Scientific studies to date have focused primarily on describing the clinical course of patients, identifying treatment options and developing vaccines. In Germany, as in many other regions, current tests for SARS-CoV2 are not conducted on a representative basis and in a longitudinal design. Furthermore, knowledge about the immune status of the population is lacking. Nonetheless, these data are needed to understand the dynamics of the pandemic and hence to appropriately design and evaluate interventions. For this purpose, we recently started a prospective population-based cohort in Munich, Germany, with the aim to develop a better understanding of the state and dynamics of the pandemic. METHODS: In 100 out of 755 randomly selected constituencies, 3000 Munich households are identified via random route and offered enrollment into the study. All household members are asked to complete a baseline questionnaire and subjects ≥14 years of age are asked to provide a venous blood sample of ≤3 ml for the determination of SARS-CoV-2 IgG/IgA status. The residual plasma and the blood pellet are preserved for later genetic and molecular biological investigations. For twelve months, each household member is asked to keep a diary of daily symptoms, whereabouts and contacts via WebApp. If symptoms suggestive for COVID-19 are reported, family members, including children < 14 years, are offered a pharyngeal swab taken at the Division of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich, for molecular testing for SARS-CoV-2. In case of severe symptoms, participants will be transferred to a Munich hospital. For one year, the study teams re-visits the households for blood sampling every six weeks. DISCUSSION: With the planned study we will establish a reliable epidemiological tool to improve the understanding of the spread of SARS-CoV-2 and to better assess the effectiveness of public health measures as well as their socio-economic effects. This will support policy makers in managing the epidemic based on scientific evidence.