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

Radon, Katja; Saathoff, Elmar; Pritsch, Michael; Noller, Jessica Michelle Guggenbühl; Kroidl, Inge; Olbrich, Laura; Thiel, Verena; Diefenbach, Maximilian N.; Riess, Friedrich; Forster, Felix; Theis, Fabian J.; Höelscher, Michael

doi:10.1101/2020.04.28.20082743

Cited by 28 publications

(35 citation statements)

References 33 publications

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“…Because of the crucial patho-mechanistic and potentially therapeutic implications, we sought to verify our findings by focusing on ISG expression at an early timepoint upon infection. To again concentrate on protective immunity, we chose a prospective cohort of ambulatory patients, which prospectively enrolled SARS-CoV 2 PCR-positive individuals, who were not hospitalized due to paucity of symptoms (validation cohort: KoCo19-Immu, see Methods) 73, 74 . We included PBMC samples early after RT-PCR-positivity (day 4) and after convalescence (day 60) (n=39).…”

Section: Resultsmentioning

confidence: 99%

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Pekayvaz

Leunig

Kaiser

et al. 2021

Preprint

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The immune system of most SARS-CoV-2 infected individuals limits viral spread to the upper airways without pulmonary involvement. This prevents the development of pneumonic COVID-19. However, the protective immunological responses causative of successful viral containment in the upper airways remain unclear. Here, we combine longitudinal single-cell RNA sequencing, proteomic profiling, multidimensional flow cytometry, RNA-Seq of FACS-sorted leukocyte subsets and multiplex plasma interferon profiling to uncover temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients. We compare host responses in a high-risk patient population infected with SARS-CoV-2 but without pulmonary involvement to patients with COVID-19 pneumonia. Our data reveal a distinct immunological signature of successful viral containment, characterized by an early prominent interferon stimulated gene (ISG) upregulation across immune cell subsets. In addition, reduced cytotoxic potential of Natural Killer (NK) and T cells, as well as a monocyte phenotype with immune-modulatory potential are hallmarks of protective immunity. Temporal resolution across disease trajectories highlights ISG upregulation as particularly prominent early in the disease and confirms increased expression also in comparison to healthy controls. We validate this distinct temporal ISG signature by in-depth RNA-seq of FACS-sorted leukocyte subsets in a large prospective ambulatory SARS-CoV-2 infected cohort confirming early and robust ISG upregulation particularly in monocytes and T cells. In conclusion, our data demonstrate a protective ISG phenotype in patients with successful containment of SARS-CoV-2 infection without progression to COVID-19. This early protective interferon response might be exploited as a therapeutic approach and for disease course prediction.

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Section: Resultsmentioning

confidence: 99%

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Pekayvaz

Leunig

Kaiser

et al. 2021

Preprint

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“…Therefore, additional data on daily deaths and hospital admissions and the number of tests performed should be considered. Furthermore, it is possible to estimate the proportion of undetected cases with the help of representative studies such as the one currently conducted in Munich, see [20]. In a recent paper [21] performed a time-varying estimation of the case detection ratio (CDR) for different age groups.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the early COVID-19 epidemic curve in Germany by regression models with change points

et al. 2021

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We analysed the coronavirus disease 2019 epidemic curve from March to the end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analysed by a trend regression model with change points. The change points are estimated directly from the data. We carry out the analysis for the whole of Germany and the federal state of Bavaria, where we have more detailed data. Both analyses show a major change between 9 and 13 March for the time series of infections: from a strong increase to a decrease. Another change was found between 25 March and 29 March, where the decline intensified. Furthermore, we perform an analysis stratified by age. A main result is a delayed course of the pandemic for the age group 80 + resulting in a turning point at the end of March. Our results differ from those by other authors as we take into account the reporting delay, which turned out to be time dependent and therefore changes the structure of the epidemic curve compared to the curve of newly reported cases.

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“…Serological studies in the region Munich indicate that during the first half of 2020 the ratio of counted people was about α = 0.25 in Germany, i.e. for each counted person there were persons entering the dark sector Radon, Saathoff and Pritschl (2020). Of course this ratio varies in space and time, for example if the number of available tests increases or, the other way round, it is too small for a rapidly increasing number of infected people.…”

Section: Selected Countries/territoriesmentioning

confidence: 99%

Studying the course of Covid-19 by a recursive delay approach

Kreck

Scholz

2021

Preprint

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In an earlier paper we proposed a recursive model for epidemics; in the present paper we generalize this model to include the asymptomatic or unrecorded symptomatic people, which we call dark people (dark sector). We call this the SEPARd-model. A delay differential equation version of the model is added; it allows a better comparison to other models. We carry this out by a comparison with the classical SIR model and indicate why we believe that the SEPARd model may work better for Covid-19 than other approaches.In the second part of the paper we explain how to deal with the data provided by the JHU, in particular we explain how to derive central model parameters from the data. Other parameters, like the size of the dark sector, are less accessible and have to be estimated more roughly, at best by results of representative serological studies which are accessible, however, only for a few countries. We start our country studies with Switzerland where such data are available. Then we apply the model to a collection of other countries, three European ones (Germany, France, Sweden), the three most stricken countries from three other continents (USA, Brazil, India). Finally we show that even the aggregated world data can be well represented by our approach.At the end of the paper we discuss the use of the model. Perhaps the most striking application is that it allows a quantitative analysis of the influence of the time until people are sent to quarantine or hospital. This suggests that imposing means to shorten this time is a powerful tool to flatten the curves.

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

Cited by 28 publications

References 33 publications

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Analysis of the early COVID-19 epidemic curve in Germany by regression models with change points

Studying the course of Covid-19 by a recursive delay approach

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