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Nature ; 594(7862): 265-270, 2021 06.
Article in English | MEDLINE | ID: covidwho-1246377


Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning-a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.

Blockchain , Clinical Decision-Making/methods , Confidentiality , Datasets as Topic , Machine Learning , Precision Medicine/methods , COVID-19/diagnosis , COVID-19/epidemiology , Disease Outbreaks , Female , Humans , Leukemia/diagnosis , Leukemia/pathology , Leukocytes/pathology , Lung Diseases/diagnosis , Machine Learning/trends , Male , Software , Tuberculosis/diagnosis
Nat Commun ; 12(1): 2117, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1174671


To estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered seroprevalence survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with an immunoassay, followed by confirmatory testing of borderline and positive test results with a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (PRNT). Those with a borderline or positive immunoassay result were retested after 4 to 5 months. At baseline, 4771 persons participated (88% response rate). Between April 24th and June 30th, 2020, seroprevalence was 0.97% (95% CI: 0.72-1.30) by immunoassay and 0.36% (95% CI: 0.21-0.61) when considering only those with two additional positive confirmatory tests. Importantly, about 20% of PRNT+ individuals lost their neutralizing antibodies within five months. Here, we show that neutralizing antibodies are detectable in only one third of those with a positive immunoassay result, and wane relatively quickly.

Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19/virology , Cohort Studies , Female , Germany , Humans , Immunoassay/methods , Male , Middle Aged , Neutralization Tests/methods , Population Surveillance/methods , SARS-CoV-2/physiology , Seroepidemiologic Studies
Genome Med ; 13(1): 7, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1027902


BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

COVID-19/pathology , Neutrophils/metabolism , Transcriptome , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Case-Control Studies , Down-Regulation , Drug Repositioning , Humans , Neutrophils/cytology , Neutrophils/immunology , Phenotype , Principal Component Analysis , RNA/blood , RNA/chemistry , RNA/metabolism , Sequence Analysis, RNA , Severity of Illness Index , Up-Regulation