Clinical trial NCT04747366: Analysis of the Pathophysiology and Pathology of Coronavirus Disease 2019 (COVID-19), Including Chronic Morbidity
Official title: National Pandemic Cohort Network - High-resolution Platform (HAP) Analysis of the Pathophysiology and Pathology of Coronavirus Disease 2019 (COVID-19), Including Chronic Morbidity
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Covid19
Keywords: COVID-19
coronavirus
SARS-CoV-2
cohort
observational
phenotyping
NAPKON-HAP
NAPKON
chronic morbidity
pa-covid
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Network University Medicine NUM
name: Berlin Institute of Health
First posted: 2021-02-10
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: COVID-19 patients, hospitalised at any of the participating hospitals (see study sites) over the age of 18 years, who are willing and deemed able to participate in the study

Brief summary: NAPKON-HAP is the deep phenotyping platform of the National Pandemic Cohort Network (NAPKON) in Germany. NAPKON is a data and biospecimen collection of patients with COVID-19 and is part of the University Medicine Network (NUM) in Germany. The primary objective of the study is to provide a comprehensive collection of data and biosamples for researchers from national consortia and for participation in international research collaborations for studying COVID-19 and future pandemics.

Data is collected from patients with COVID-19 three times per week during their hospitalization and at follow-up visits after hospital discharge 3, 6, 12, 24, and 36 months after symptom onset. Data include epidemiological and demographic parameters, medical history and potential risk factors, documentation of routine medical procedures, and clinical course, including different patterns of organ involvement, quality of care, morbidity, and quality of life. Moreover, extensive serial high-quality bio sampling consisting of various sample types is performed to allow deep molecular, immunological, and virological phenotyping.

Patients not requiring Intensive Care Unit (ICU)/ Intermediate Care (IMC) treatment will receive 7 and patients requiring ICU/IMC treatment will receive 16 full-phenotyping visits including sampling for biobanking. During hospitalisation the planned blood sampling rate in total is 35 ml at each visit. The total amounts and/or sampling dates may differ according to the ethics committee's regulations for different study centers.

At follow-up visits, the clinical assessment includes an update of the medical history and recent medical events from which additional clinical data is collected (i.e. outpatient CT-scans, echocardiography, external laboratory data). Clinical symptoms are recorded and a physical examination will be performed. Vital signs are recorded and routine blood testing and biosampling is continued. Quality of life is measured with patient-reported outcome questionnaires.

Follow-up visits at months 3 and 12 are "deep phenotyping" visits with a comprehensive and detailed set of examinations. In the following visits at months 24 and 36, only examinations with pathologic results from the last deep phenotyping visit at month 12 will be performed.

A shorter follow-up visit to record quality of life, recent medical events and with a reduced number of examinations focusing on cardiorespiratory performance will take place at month 6.

In case of relevant medical events, new medical information or changes in the participant´s health status, an unscheduled visit can take place anytime within the entire study period.

Data collection during follow up includes standardized quality of life assessment including PROMIS® (Patient-Reported Outcomes Measurement Information System). The pulmonary characterization will include body plethysmography, diffusion capacity, respiratory muscles strength measurement, spiroergometry, capillary blood gas analysis and lung imaging studies (low-dose Computed Tomography (CT), Magnetic Resonance Imaging (MRI) of the lung). Cardiological phenotyping includes echocardiography, electrocardiogram (ECG), 24h-ECG, 24h-blood pressure monitoring, stress cardiac MRI and pulse wave analysis. Neurocognitive testing includes brain MRI, electroencephalogram (EEG), somatosensory testing, refractometry (Visit 3 and 12 months), physical activity test, neurocognitive tests, somatosensory phenotyping, taste- and smell-test. Endocrinological phenotyping will incorporate Advanced Glycation Endproducts (AGE) reader, continuous glucose monitoring for 14 days, Air Displacement Plethysmography (ADP) or bioelectrical impedance analysis (BIA).


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Willingness to participate in the study (consent to participate by patient or appropriate legal representative) or inclusion via deferred consent
* Hospitalization at time of enrollment
* Positive evidence for SARS-CoV-2 infection with PCR (polymerase chain reaction) or initial positive rapid diagnostic test in conjunction with typical clinical symptoms, confirmed by a later positive PCR test.

Exclusion Criteria:

* Refusal to participate by patient, or appropriate legal representative
* Any condition that prohibits supplemental blood-sampling beyond routine blood drawing

Primary outcomes:
measure: Changes in Patient-reported Quality of life recorded with the help of the European Quality of Life 5 Dimensions 5 Level Version (Eq5d5l) questionnaire
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the Short Form Health 36 (Sf36)
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the Patient-Reported Outcomes Measurement Information System (PROMIS Profile)
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the Neuropathy Questionnaire (Mnsi)
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the Trauma Patient Health Questionnaire
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the PTSD (Post-traumatic stress disorder) Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5).
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the National Eye Institute Visual Function Questionnaire (NEI-VFQ)
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in Patient-reported Quality of life recorded with the help of the St. George's Respiratory Questionnaire (SGRQ)
timeFrame: day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset
measure: Changes in neruocognitive testing with Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in neruocognitive testing with Montreal Cognitive Assessment Test (MOCA)
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in blood pressure measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in sensomotory testing with the questionnaire for peripheral neuropathy (Michigan Neuropathy Screening Instrument, MNSI)
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in sensomotory testing with the questionnaire (painDETECT-questionnaire, pDQ)
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in Quantitative sensory testing (QST)
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in Point-of-care neurography
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in pulmonary function assessed by body plethysmography
timeFrame: immediately before discharge, at follow-up visits (3, 6 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in pulmonary function assessed by single breath CO (carbon monoxide) diffusion capacity (DLCO)
timeFrame: immediately before discharge, at follow-up visits (3, 6 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in heart rate measured with ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the oxygen saturation of the blood measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the total concentration of carbon dioxide (ctCO2) of the blood measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the pH value of the blood measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the bicarbonate content of the blood measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the blood lactate levels during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in the partial pressure of carbon dioxide (pCO2) of the blood measured during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in heart rhythm type measured with ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results
measure: Changes in time intervals of PQ measured with ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in time intervals of QRS measured with ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Changes in time intervals of QT measured with ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
measure: Deviations in the ST segment depicted with the use of ECG (Electrocardiogram) during spiroergometry testing
timeFrame: at follow-up visits (3 and 12 months after symptom onset and 24 and 36 months after symptom onset (only in case of abnormal results)
Secondary outcomes:
measure: Changes in body temperature
timeFrame: every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks
measure: Changes in blood pressure
timeFrame: every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks
measure: Changes in heart rate
timeFrame: every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks
measure: Changes in breath frequency (respiratory rate)
timeFrame: every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks
measure: Changes in peripheral oxygen saturation
timeFrame: every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks
measure: Changes in the clinical score SOFA (sequential organ failure assessment)
timeFrame: at primary admission to hospital, upon admission to ICU ward, every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score Berlin ARDS (acute respiratory distress syndrome) severity score (if provided)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score APACHE (Acute Physiology and Chronic Health Evaluation) Score
timeFrame: upon admission to ICU
measure: Changes in the clinical score NEWS (National Early Warning Score)
timeFrame: day 1 of enrollment in the study (day of hospitalization), if available
measure: Changes in the clinical score qSOFA Score (quick sequential organ failure assessment)
timeFrame: day 1 of enrollment in the study (day of hospitalization), if available
measure: Changes in the Barthel Index
timeFrame: day 1 of enrollment in the study, every Monday, Wednesday and Friday during hospitalisation, (assessed up to 100 weeks?), immediately before discharge, at follow up visits 3, 12, 24 and 36 months after symptom onset
measure: Changes in the Frailty score
timeFrame: day 1 of enrollment in the study, every Monday, Wednesday and Friday during hospitalisation, (assessed up to 100 weeks?), immediately before discharge, at follow up visits 3, 12, 24 and 36 months after symptom onset
measure: Changes in the clinical score Murray Score
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score Glasgow Coma Scale (GCS)
timeFrame: upon admission to ICU ward, every Monday, Wednesday and Friday ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score RASS (Richmond Agitation Sedation Scale)
timeFrame: upon admission to ICU ward, every Monday, Wednesday and Friday ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score CAM-ICU (Score Confusion Assessment Method for Intensive Care Unit)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay,assessed up to 100 weeks
measure: Changes in the clinical score SAPSII (Simplified acute physiology Score II)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score NRS (numeric rating scale) pain score
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score BPS (behavioural pain scale) pain score
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score CPOT (Critical Care Pain Observation tool)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the clinical score DDS (Delirium detection score)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the checked items on the ICDSC (Intensive Care Delirium Screening checklist)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the heart time volume
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the cardiac index
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in EVLWI (Extravascular Lung Water Index)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in Systemic Vascular Resistance Index (SVRI)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in ITBVI (Intrathoracic Blood Volume Index)
timeFrame: every Monday, Wednesday and Friday during ICU ward stay, assessed up to 100 weeks
measure: Changes in the score WHO (World Health Organisation) clinical ordinal scale
timeFrame: every day during hospital stay (from day of admission until discharge from hospital, assessed up to 100 weeks) and at follow-up visits (3, 12, 24 and 36 months after symptom onset)
measure: Changes in the NYHA (New York Heart Association) score
timeFrame: at deep phenotyping during follow-up visits (3 and 12 months after symptom onset)
measure: Changes in the Post-COVID-19 Functional Status (PCFS) scale
timeFrame: at follow-up visits (3, 12, 24 and 36 months after symptom onset)
measure: Changes in the National Institutes of Health Stroke Scale (NIHSS)
timeFrame: at deep phenotyping during follow-up visits (3 and 12 months after symptom onset)
measure: Changes in the Katz Index
timeFrame: at follow-up visits (3, 12, 24 and 36 months after symptom onset)
measure: Changes in the Rose Dyspnea Scale
timeFrame: at deep phenotyping during follow-up visits (3 and 12 months after symptom onset)
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University Medical Center Freiburg Department of Internal Medicine II Department of Infectiology
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg Clinic for Gastroenterology, Infections, Poisoning
state: Baden-Württemberg
city: Munich
country: Germany
facility: Clinic of the University of Munich Medical Clinic and Polyclinic III
state: Bayern
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt Medical Clinic II Department of infectiology
state: Hessen
city: Gießen
country: Germany
facility: University Hospital Giessen (+Marburg) Medical Clinic II Pneumology and internal intensive care medicine Infectiology, Gastroenterology, Nephrology
state: Hessen
city: Hannover
country: Germany
facility: Hanover Medical School Clinic for Pneumology
state: Niedersachsen
city: Cologne
country: Germany
facility: University Hospital Cologne Internal Medicine I and Hematology and Oncology, Infectiology, additional qualification in Emergency Medicine
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein (Campus Kiel): Internal medicine, gastroenterology, pneumology, allergology, sleep medicine, emergency medicine, intensive care
state: Schleswig-Holstein
city: Lübeck
country: Germany
facility: University Medical Center Schleswig-Holstein (Campus Lübeck): Internal medicine, gastroenterology, pneumology, allergology, sleep medicine, emergency medicine, intensive care
state: Schleswig-Holstein
city: Jena
country: Germany
facility: University Hospital Jena Department of Internal Medicine IV
state: Thüringen
city: Berlin
country: Germany
facility: Charité University Hospital Berlin Medical Clinic Infectiology and Pneumology CCM/CVK
Study officials:
affiliation: Charite University Hospital Berlin
name: Martin Witzenrath, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schons M, Pilgram L, Reese JP, Stecher M, Anton G, Appel KS, Bahmer T, Bartschke A, Bellinghausen C, Bernemann I, Brechtel M, Brinkmann F, Brunn C, Dhillon C, Fiessler C, Geisler R, Hamelmann E, Hansch S, Hanses F, Hanss S, Herold S, Heyder R, Hofmann AL, Hopff SM, Horn A, Jakob C, Jiru-Hillmann S, Keil T, Khodamoradi Y, Kohls M, Kraus M, Krefting D, Kunze S, Kurth F, Lieb W, Lippert LJ, Lorbeer R, Lorenz-Depiereux B, Maetzler C, Miljukov O, Nauck M, Pape D, Puntmann V, Reinke L, Rommele C, Rudolph S, Sass J, Schafer C, Schaller J, Schattschneider M, Scheer C, Scherer M, Schmidt S, Schmidt J, Seibel K, Stahl D, Steinbeis F, Stork S, Tauchert M, Tebbe JJ, Thibeault C, Toepfner N, Ungethum K, Vadasz I, Valentin H, Wiedmann S, Zoller T, Nagel E, Krawczak M, von Kalle C, Illig T, Schreiber S, Witzenrath M, Heuschmann P, Vehreschild JJ; NAPKON Research Group. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. Eur J Epidemiol. 2022 Aug;37(8):849-870. doi: 10.1007/s10654-022-00896-z. Epub 2022 Jul 29.