Analysis of the Pathophysiology and Pathology of Coronavirus Disease 2019 (COVID-19), Including Chronic Morbidity

NCT04747366 | Unknown DMC

• 1 other identifier: NAPKON-HAP
• Study Type: observational
• Target: 750
• Locations: 1 country
• Sites: 11

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).

Conditions

Covid19

Keywords

COVID-19; coronavirus; SARS-CoV-2; cohort; observational; phenotyping; NAPKON-HAP; NAPKON; chronic morbidity; pa-covid

Outcome Measures

Primary Outcomes (29)

• Changes in Patient-reported Quality of life recorded with the help of the European Quality of Life 5 Dimensions 5 Level Version (Eq5d5l) questionnaire

  Health related quality of life after hospital discharge will be assessed with the questionnaire European Quality of Life 5 Dimensions 5 Level Version (Eq5d5l)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the Short Form Health 36 (Sf36)

  Health related quality of life after hospital discharge will be assessed with the questionnaire Short Form Health 36 (Sf36)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the Patient-Reported Outcomes Measurement Information System (PROMIS Profile)

  Health related quality of life after hospital discharge will be assessed with the questionnaire Patient-Reported Outcomes Measurement Information System (PROMIS Profile)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the Neuropathy Questionnaire (Mnsi)

  Health related quality of life after hospital discharge will be assessed with the questionnaire Neuropathy Questionnaire (Mnsi)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the Trauma Patient Health Questionnaire

  Health related quality of life after hospital discharge will be assessed with the questionnaire Trauma Patient Health Questionnaire

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• 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).

  Health related quality of life after hospital discharge will be assessed with the PTSD (Post-traumatic stress disorder) Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5). The PTSD Checklist for DSM-5 is a 20-questions self-report measure that assesses the presence and severity of PTSD symptoms.

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the National Eye Institute Visual Function Questionnaire (NEI-VFQ)

  Health related quality of life after hospital discharge will be assessed with the questionnaire National Eye Institute Visual Function Questionnaire (NEI-VFQ)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in Patient-reported Quality of life recorded with the help of the St. George's Respiratory Questionnaire (SGRQ)

  Health related quality of life after hospital discharge will be assessed with the questionnaire St. George's Respiratory Questionnaire (SGRQ)

  day 1 of enrollment in the study, immediately before discharge, 3, 12, 24 and 36 months after symptom onset

• Changes in neruocognitive testing with Cambridge Neuropsychological Test Automated Battery (CANTAB)

  CANTAB tests can detect changes in neuropsychological performance and include tests of working memory, learning and executive function; visual, verbal and episodic memory; attention, information processing and reaction time; social and emotion recognition, decision making and response control.

  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)

• Changes in neruocognitive testing with Montreal Cognitive Assessment Test (MOCA)

  This test is a screening procedure to determine cognitive deficits. Central cognitive functions are examined using 11 task complexes. This includes time and spatial orientation, learning and memory, attention, language and language skills, reading, writing, drawing and calculating (test duration approx. 10 minutes).

  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)

• Changes in blood pressure measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Using spiroergometry blood pressure is measured during the test and compared with normative values.

  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)

• Changes in sensomotory testing with the questionnaire for peripheral neuropathy (Michigan Neuropathy Screening Instrument, MNSI)

  The MNSI will be used to screen patients for peripheral neuropathy.

  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)

• Changes in sensomotory testing with the questionnaire (painDETECT-questionnaire, pDQ)

  PainDETECT will be used to screen patients for for neuropathic pain.

  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)

• Changes in Quantitative sensory testing (QST)

  Quantitative sensory testing (QST) is a method for semiquantative evaluation of somatosensory nervous system disorders, including chronic pain and pain related to various diseases. It essentially determines the sensation and pain thresholds for cold and warm temperatures, and the vibration sensation threshold by stimulating the skin and comparing the results to normative values.

  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)

• Changes in Point-of-care neurography

  Point-of-care neuography measures nerve conduction using a point-of-care device (DPNcheck, Neurometrix Inc, USA).

  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)

• Changes in pulmonary function assessed by body plethysmography

  Body plethysmography will yield information on the static and dynamic lung volumes to assess obstructive and restrictive ventilation patterns.

  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)

• Changes in pulmonary function assessed by single breath CO (carbon monoxide) diffusion capacity (DLCO)

  The DLCO test provides a general assessment of the lungs' ability to take up oxygen from the inspiratory air and to release carbon dioxide.

  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)

• Changes in heart rate measured with ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The patient´s heart rate will be assessed longitudinally and compared to normative values.

  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)

• Changes in the oxygen saturation of the blood measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Two blood samples are taken 2 hours apart. The first one is taken before the spiroergometry test and the second one - 120 minutes after the first one. The total concentration of carbon dioxide (ctCO2) of the blood is measured and compared with normative values.

  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)

• Changes in the total concentration of carbon dioxide (ctCO2) of the blood measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. The carbon dioxide content of the blood is measured during the test and compared with normative values.

  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)

• Changes in the pH value of the blood measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Two blood samples are taken 2 hours apart. The first one is taken before the spiroergometry test and the second one - 120 minutes after the first one. The pH value of the blood is measured and compared with normative values. The pH value describes how acidic or basic the blood is.

  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)

• Changes in the bicarbonate content of the blood measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Two blood samples are taken 2 hours apart. The first one is taken before the spiroergometry test and the second one - 120 minutes after the first one. The bicarbonate content of the blood is measured and compared with normative values. Bicarbonate is a form of carbon dioxide.

  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)

• Changes in the blood lactate levels during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Two blood samples are taken 2 hours apart. The first one is taken before the spiroergometry test and the second one - 120 minutes after the first one. The lactate saturation is measured and compared with normative values.

  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)

• Changes in the partial pressure of carbon dioxide (pCO2) of the blood measured during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. Two blood samples are taken 2 hours apart. The first one is taken before the spiroergometry test and the second one - 120 minutes after the first one. The partial pressure of carbon dioxide (pCO2) of the blood is measured and compared with normative values.

  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)

• Changes in heart rhythm type measured with ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The patient´s heart rhythm will be assessed. Any abnormalities (too slow, too fast, irregular) will be documented and subsequently clinical consequences are being taken.

  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

• Changes in time intervals of PQ measured with ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The time interval of PQ corresponds to the time interval from the beginning of the P wave to the beginning of the Q wave of the QRS complex. The time interval of PQ gives us information about the time required for the action potential to be transmitted from the atria to the ventricles. The recorded PQ time will be compared to normative values. In case of delayed PQ times, further diagnostic is carried out according to current guidelines.

  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)

• Changes in time intervals of QRS measured with ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The QRS complex is combination of the Q wave, R wave and S wave. The time interval of QRS corresponds to the time needed for ventricular depolarization. The recorded QRS time will be compared to normative values. In case of new diagnosed bundle blocks, further diagnostic is carried out according to current guidelines.

  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)

• Changes in time intervals of QT measured with ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The time interval of QT corresponds to the time interval from the beginning of the Q wave to the end of the T wave. The time interval of QT gives us information about the time required for ventricular depolarisation and repolarisation. The recorded QT time will be compared to normative values. In case of abnormal QT times, further diagnostic is carried out according to current guidelines.

  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)

• Deviations in the ST segment depicted with the use of ECG (Electrocardiogram) during spiroergometry testing

  Spiroergometry (spirometry while the participant exercises on a bicycle ergometer) is used to evaluate physical performance and fitness. ECG is a test, used to monitor the electrical activity of the heart. Standard placement of 12-lead electrodes will be used. The ST-segment is a section between the end of the S wave and the beginning of the T wave and reflects the depolarized state and initial repolarization of the ventricles. Deviations in the ST segment (elevation or depression) will be documented. In case of ST segment elevation or depression, further diagnostic is carried out according to current guidelines.

  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 (33)

• Changes in body temperature

  every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks

• Changes in blood pressure

  every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks

• Changes in heart rate

  every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks

• Changes in breath frequency (respiratory rate)

  every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks

• Changes in peripheral oxygen saturation

  every day during hospitalisation (from date of admission in trial until date of discharge or date of death, assessed up to 100 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Age ≥ 18 years
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Network University Medicine NUM: collaborator
• Berlin Institute of Health: collaborator

Study Sites (11)

University Medical Center Freiburg Department of Internal Medicine II Department of Infectiology

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

University Hospital Heidelberg Clinic for Gastroenterology, Infections, Poisoning

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Clinic of the University of Munich Medical Clinic and Polyclinic III

Munich, Bavaria, 81377, Germany

RECRUITING

University Hospital Frankfurt Medical Clinic II Department of infectiology

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

University Hospital Giessen (+Marburg) Medical Clinic II Pneumology and internal intensive care medicine Infectiology, Gastroenterology, Nephrology

Giessen, Hesse, 35392, Germany

RECRUITING

Hanover Medical School Clinic for Pneumology

Hanover, Lower Saxony, 30625, Germany

RECRUITING

University Hospital Cologne Internal Medicine I and Hematology and Oncology, Infectiology, additional qualification in Emergency Medicine

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

University Medical Center Schleswig-Holstein (Campus Kiel): Internal medicine, gastroenterology, pneumology, allergology, sleep medicine, emergency medicine, intensive care

Kiel, Schleswig-Holstein, 24105, Germany

RECRUITING

University Medical Center Schleswig-Holstein (Campus Lübeck): Internal medicine, gastroenterology, pneumology, allergology, sleep medicine, emergency medicine, intensive care

Lübeck, Schleswig-Holstein, 23538, Germany

RECRUITING

University Hospital Jena Department of Internal Medicine IV

Jena, Thuringia, 07747, Germany

RECRUITING

Charité University Hospital Berlin Medical Clinic Infectiology and Pneumology CCM/CVK

Berlin, 13353, Germany

RECRUITING

Related Publications (3)

• Hartung TJ, Steigerwald F, Romanello A, Kodde C, Endres M, Frank S, Heuschmann P, Koehler P, Krohn S, Pape D, Schaller J, Stocklein S, Vadasz I, Vehreschild J, Witzenrath M, Zoller T, Finke C; NAPKON Study Group. Post-COVID Fatigue Is Associated With Reduced Cortical Thickness After Hospitalization. Ann Clin Transl Neurol. 2025 Nov 25. doi: 10.1002/acn3.70260. Online ahead of print.

  PMID: 41288256 DERIVED

• Appel KS, Lee CH, Nunes de Miranda SM, Maier D, Reese JP, Anton G, Bahmer T, Ballhausen S, Balzuweit B, Bellinghausen C, Blumentritt A, Brechtel M, Chaplinskaya-Sobol I, Erber J, Fiedler K, Geisler R, Heyder R, Illig T, Kohls M, Kollek J, Krist L, Lorbeer R, Miljukov O, Mitrov L, Nurnberger C, Pape C, Pley C, Schafer C, Schaller J, Schattschneider M, Scherer M, Schulze N, Stahl D, Stubbe HC, Tamminga T, Tebbe JJ, Vehreschild MJGT, Wiedmann S, Vehreschild JJ. A precise performance-based reimbursement model for the multi-centre NAPKON cohorts - development and evaluation. Sci Rep. 2024 Jun 13;14(1):13607. doi: 10.1038/s41598-024-63945-5.

  PMID: 38871878 DERIVED

• 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.

  PMID: 35904671 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Saliva, Urin, Oropharyngeal / Nasopharyngeal swab / Bronchoalveolar lavage (BAL) / Endotracheal aspirate (ENTA), whole blood

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Martin Witzenrath, Prof. Dr. med.

  Charite University Hospital Berlin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Witzenrath, Prof. Dr. med.

CONTACT

+49 30 450 553 892; martin.witzenrath@charite.de

Florian Kurth, PD Dr.

CONTACT

florian.kurth@charite.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: February 10, 2021
• Study Start: November 6, 2020
• Primary Completion: November 1, 2025
• Study Completion: November 30, 2025
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)