Studying the pathophysiology of coronavirus disease 2019 – a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19)

Kurth, Florian; Roennefarth, Maria; Thibeault, Charlotte; Corman, Victor M.; Mueller-Redetzky, Holger; Mittermaier, Mirja; Ruwwe-Gloesenkamp, Christoph; Krannich, Alexander; Kretzler, Lucie; Dang-Heine, Chantip; Rose, Matthias; Hummel, Michael; Hocke, Andreas C.; Huebner, Ralf H.; Mall, Marcus; Roehmel, Jobst; Landmesser, Ulf; Pieske, Burkert; Knauß, Samuel; Endres, Matthias; Spranger, Joachim; Mockenhaupt, Frank P.; Tacke, Frank; Treskatsch, Sascha; Angermair, Stefan; Siegmund, Britta; Spies, Claudia; Weber‐Carstens, Steffen; Uhrig, Alexander; Zöller, Thomas; Drosten, Christian; Suttorp, Norbert; Witzenrath, Martin; Hippenstiel, Stefan; Kalle, Christoph von; Sander, Leif Erik

doi:10.1101/2020.05.06.20092833

Cited by 19 publications

(26 citation statements)

References 25 publications

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“…Patients were recruited within the Pa-COVID-19 study conducted at Charité - Universitätsmedizin Berlin, a prospective observational cohort study on the pathophysiology of COVID-19. The study protocol has been described in detail before 100 . All patients with PCR-confirmed SARS-CoV-2 infection were eligible for inclusion.…”

Section: Methodsmentioning

confidence: 99%

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Demichev¹,

Tober‐Lau²,

Nazarenko³

et al. 2020

Preprint

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COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.

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Section: Methodsmentioning

confidence: 99%

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Demichev¹,

Tober‐Lau²,

Nazarenko³

et al. 2020

Preprint

Self Cite

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show abstract

“…Data collection was performed within the Pa-COVID-19 study, a prospective observational cohort study conducted at Charité – Universitätsmedizin Berlin, as described [14]. Adult patients admitted between March 1 st and June 30 th , 2020, with PCR-confirmed SARS-CoV-2 infection were included if patients or their legal representatives gave informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we report clinical characteristics, laboratory and virological parameters, clinical course, and outcome of 168 COVID-19 patients included in a prospective observational cohort study conducted at Charité – Universitätsmedizin Berlin, Germany. The study was designed for deep clinical, molecular, and immunological phenotyping of COVID-19 [14-18].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Virological Characteristics of Hospitalized COVID-19 Patients in a German Tertiary Care Center during the First Wave of the SARS-CoV-2 Pandemic

Thibeault

Muehlemann

Helbig

et al. 2020

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BackgroundAdequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories.MethodsA cohort of 168 hospitalized adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care center was analyzed.ResultsForty-four percent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95%CI 1.10-1.37, p<0.01), age 60-69 as compared to 18-59 years (aOR 4.33, 95%CI 1.07-20.10, p=0.04), and history of hypertension (aOR 5.55, 95%CI 2.00-16.82, p<0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p<0.01). Median duration of hospitalization was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV-patients.ConclusionOur results indicate a short duration of symptoms before admission as a risk factor for severe disease and different viral load kinetics in severely affected patients.

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“…Charite Universitätsmedizin Berlin procedures were performed within the framework of the Pa-COVID-19 protocol 18 .…”

Section: Ethics Committee Approvalmentioning

confidence: 99%

HLA-C^*04:01 is a Genetic Risk Allele for Severe Course of COVID-19

Weiner

Suwalski

Holtgrewe

et al. 2020

Preprint

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BackgroundSince the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing demand to identify predictors of severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors. We sought to evaluate this hypothesis by conducting an international multicenter study using HLA sequencing with subsequent independent validation.MethodsWe analyzed a total of 332 samples. First, we enrolled 233 patients in Germany, Spain, and Switzerland for HLA and whole exome sequencing. Furthermore, we validated our results in a public data set (United States, n=99). Patients older than 18 years presenting with COVID-19 were included, representing the full spectrum of the disease. HLA candidate alleles were identified in the derivation cohort (n=92) and tested in two independent validation cohorts (n=240).ResultsWe identified HLA-C* 04:01 as a novel genetic predictor for severe clinical course in COVID-19. Carriers of HLA-C* 04:01 had twice the risk of intubation when infected with SARS-CoV-2 (hazard ratio 2.1, adjusted p-value=0.0036). Importantly, these findings were successfully replicated in an independent data set. Furthermore, our findings are biologically plausible, as HLA-C* 04:01 has fewer predicted bindings sites with relevant SARS-CoV-2 peptides as compared to other HLA alleles. Exome sequencing confirmed findings from HLA analysis.ConclusionsHLA-C* 04:01 carriage is associated with a twofold increased risk of intubation in patients infected with SARS-CoV-2. Testing for HLA-C* 04:01 could have clinical implications to identify high-risk patients and individualize management.

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Studying the pathophysiology of coronavirus disease 2019 – a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19)

Cited by 19 publications

References 25 publications

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Clinical and Virological Characteristics of Hospitalized COVID-19 Patients in a German Tertiary Care Center during the First Wave of the SARS-CoV-2 Pandemic

HLA-C^*04:01 is a Genetic Risk Allele for Severe Course of COVID-19

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Studying the pathophysiology of coronavirus disease 2019 – a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19)

Cited by 19 publications

References 25 publications

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome

Clinical and Virological Characteristics of Hospitalized COVID-19 Patients in a German Tertiary Care Center during the First Wave of the SARS-CoV-2 Pandemic

HLA-C*04:01 is a Genetic Risk Allele for Severe Course of COVID-19

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Product

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HLA-C^*04:01 is a Genetic Risk Allele for Severe Course of COVID-19