Munich Long COVID Registry Study for Children, Adolescents and Adults (MLC-R), COVID-19, SARS-CoV-2

Sponsor

Technical University of Munich (Other)

Overall Status

Recruiting

CT.gov ID

NCT05638724

Collaborator

Kliniken für Kinder- und Jugendmedizin der Charité Berlin (Other), Universitätskinderklinik Bochum (Other), Ruhr-Universität Bochum, Klinische Kinderpsychologie (Other), Universitätsklinikum der Technischen Universität Dresden (Other), Universitätsklinikum Freiburg (Other), Universitätsklinikum Hamburg-Eppendorf (Other), Hannover Medical School (Other), University Hospital, Saarland (Other), Universitätskinderklinik Jena (Other), Klinikum Kassel (Other), Uniklinik Köln (Other)

1,000

Enrollment

Location

Anticipated Duration (Months)

16.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Long COVID refers to persistent symptoms after a generally mild acute COVID-19. Because the symptoms are often complex and vary from person to person, the term post-COVID syndrome is used synonymously. In the ICD-10 catalog, Long COVID is mapped as U09.9 as "post-COVID-19 conditions." Long COVID carries a high risk for chronic morbidity. This has serious consequences for individuals and society, especially when manifesting in young adulthood, adolescence, and childhood. Current data show that predominantly young women aged 30-40 years are affected by severe Long COVID. Despite only mild acute COVID-19, 10-15% of patients still show persistent symptoms six months later, including particularly frequently pathological exhaustion (fatigue), exercise intolerance with symptom worsening after exertion (so-called post-exertional malaise), neurocognitive complaints and circulatory disorders. In addition, general symptoms such as sleep disturbances, pain, or subfebrile temperatures have been described, as well as symptoms of all organ systems.

In children and adolescents, less prevalence data are available to date. In initial studies, 4.4% and 4.6% of children and adolescents, respectively, show persistent symptoms after four weeks, 9.8% of 2-11 year olds and 13% of 12-16 year olds after five weeks, and 1.8% of children and adolescents with confirmed/probable SARS-CoV-2 infection after two months.

Long COVID often results in impairment of daily life with limited ability to go to school or to work, up to and including inability to go to school or to work. Some patients manifest full-blown CFS, which has also been described after other viral infections, such as after glandular fever caused by Epstein-Bar virus (EBV). Similar to post-COVID CFS, CFS after primary EBV infection manifests predominantly in female adolescents and young adults. Whether it is the same severe, chronic disease despite similar clinical phenotype is uncertain.

The mechanisms of pathogenesis of Long COVID and postinfectious CFS have been poorly elucidated. Initial studies of Long COVID suggest that autoimmunity, chronic inflammation, endothelial dysfunction, and psychosocial aspects contribute to pathogenesis. For postinfectious CFS, a causal interplay of genetic factors, stress, and infections has also been postulated, inducing a vicious cycle of dysregulation of the central and autonomic nervous system, immune defense, and metabolism.

Condition or Disease	Intervention/Treatment	Phase
Long COVID

Detailed Description

Infections with the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) and the resulting "coronavirus disease 2019" (COVID-19) have been observed in Germany since January 2020 and subsequently represent a risk for the development of a complex chronic disease, which is referred to as Long COVID.

Long COVID describes the persistence of symptoms over a period of more than four weeks from the onset of acute COVID-19. If the symptoms persist for more than twelve weeks, they are also referred to as post-COVID syndrome according to the NICE guideline. Other causes for the symptoms must be excluded.

Patients experience a variety of symptoms, including fatigue, exercise intolerance with worsening of symptoms after low exertion (post-exertional malaise, PEM), brain fog, cardiac and/or pulmonary symptoms.

Long COVID occurs in most cases after initially mild COVID-19. The age spectrum includes mainly young adults, although it also occurs in adolescents and children. In adults, approximately 10-15% of patients with COVID-19 Long are thought to develop COVID symptoms.

In childhood, the number is likely to be much lower. With only limited data, a prevalence of 2-10% is discussed. Among these, the risk for adolescents appears to be higher and closer to the risk for adults than for younger children.

There appears to be a predominance of females in all age groups. Some affected individuals manifest full-blown postinfectious chronic fatigue syndrome (CFS).

Due to the high number of cases for COVID-19 worldwide, the prevalence of Long COVID is also expected to increase. The increase is also reflected in the inquiry statistics at our MRI Chronic Fatigue Center for Young People (MCFC). Many affected individuals are severely limited in their quality of life by Long COVID, and in some cases are unable to attend school or work. Therefore, the disease represents a major health and socioeconomic problem for society.

While progress has been made in deciphering the pathogenesis of acute COVID-19, the mechanisms of Long COVID are poorly understood and have been poorly studied. There is increasing evidence that alterations in the microcirculation and autonomic nervous system may occur due to damage from the virus itself or from persistent inflammation or autoimmunologic processes, including the emergence of autoantibodies. For postinfectious CFS, a similar interplay of genetic factors, stress, and infections has been postulated to induce a vicious cycle leading to dysregulation of the central and autonomic nervous systems, immune defenses, and metabolism.

Analogous to post-infectious CFS, patients* with Long COVID present with marked fatigue and exercise intolerance with PEM accompanied by pain, sleep disturbances, neurocognitive manifestations, circulatory complaints, and other complex symptoms that impair daily functioning. However, the spectrum of symptomatology in patients* with Long COVID is currently not fully explored. The international literature on minors and very young adults with Long COVID is scarce and largely based on patient interviews without medical visits with appropriate differential diagnosis or seroepidemiological studies.

The MCFC of the Polyclinic for Pediatrics and Adolescent Medicine of the Klinikum rechts der Isar, cares for children, adolescents and young adults up to 25 years of age with post-infectious fatigue or post-infectious CFS and increasingly patients with Long COVID.

Children and adolescents with Long COVID are evaluated and cared for in the university and polyclinic clinics for pediatric and adolescent medicine of the Charité, the University Children's Hospital Bochum, the Carl Gustav Carus University Hospital at the Technical University of Dresden, the University Hospital Freiburg, the University Hospital Hamburg-Eppendorf, the Saarland University Hospital, the University Children's Hospital Jena, the Kassel Hospital, and the University Hospital Cologne.

After a detailed differential diagnosis to exclude organic or psychological causes of the symptoms, a structured anamnesis is taken by means of various questionnaires and the disease of the patients is further phenotyped clinically by laboratory analyses, functional tests and imaging during the presentation at the MCFC and the other clinics mentioned. A common data collection in these study centers has not been established yet.

These extensive medical data from the specialized routine care should be recorded, compiled and made available for research in a standardized, multicenter, longitudinal and, if possible, web-based manner with the help of the proposed Munich Long COVID Registry Study (MLC-R). Prospectively, there is the possibility of recruiting further study centers.

The digital implementation is to be carried out in cooperation with the Munich IT company Bitcare GmbH. Their database concepts have proven themselves in the context of the Transplantation Cohort (Tx Cohort) of the German Center for Infection Research (DZIF) or the COVID-19 study of the MRI of the TUM (COMRI). With support from Bitcare GmbH, our research group is currently establishing a Germany-wide ME/CFS registry.

The aim of the MLC-R is to describe the clinical picture and its course in Germany in a clinically precise manner and, if necessary, to derive epidemiological or medical risk factors, to record the need for care more precisely and to define subcohorts for future treatment approaches.

Primary objective of the study:

Phenotyping of Long COVID through a transition-oriented, longitudinal collection of epidemiological, medical and health care data in a web-based, multicenter registry study

Secondary Objectives of the study:

Generate epidemiologic, medical, and health care data as a basis for innovative care concepts, political measures and public relations.
Define subcohorts and baseline data for clinical trials.
Recording the frequency of comorbidities
Identification of diagnostic parameters
Estimation of prognosis
Identification of treatment approaches
Harmonization of diagnosis
Harmonization of epidemiological and clinical data collection
Networking of dedicated treatment centers
Perspective improvement of care by training of new centers regarding the standardized data collection.
In case of broad consent, storage of residual materials collected in the course of routine care

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Munich Long COVID Registry Study for Children, Adolescents and Adults (MLC-R)

Actual Study Start Date :

Jul 20, 2022

Anticipated Primary Completion Date :

Jul 20, 2027

Anticipated Study Completion Date :

Jul 20, 2027

Outcome Measures

Primary Outcome Measures

Phenotyping Long COVID by inclusion of as many affected patients as possible in a transition-oriented, longitudinal collection of data in a web-based, multicenter registry study. [5 years]
Extensive data are collected from the patients included in the study on questions such as epidemiologic, medical, and health care data.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Inclusion Criteria:

Written consent of the patient or, in the case of children and adolescents, written consent of the patient and written consent of the legal guardian.

II. condition following confirmed or highly probable SARS-CoV-2 infection:

Detection of SARS-CoV-2 infection by polymerase chain reaction (PCR).
Detection of SARS-CoV-2 infection by rapid antigen test (AST) in the context of matching COVID-19 symptoms.
Clinical diagnosis of COVID-19 with the aid of typical CT findings or on the basis of a present olfactory and gustatory disturbance.
History of high-risk contact with subsequent plausible COVID-19 symptomatology.
Detection of anti-SARS-CoV-2-N and/or -S-IgG antibodies following anamnestic plausible COVID-19 symptomatology.
Future valid biomarkers

III. suspected diagnosis according to ICD-10:

U09.9 ! (V) Post-COVID-19 condition, unspecified.
U12.9 ! (V) Adverse reactions to COVID-19 vaccine use, unspecified.

Exclusion Criteria:

Retrospectively available medical data that are not compatible with the inclusion criteria may lead to subsequent exclusion from the study.
Patients whose entire clinical picture, but not individual symptoms, can be explained by another underlying disease according to WHO.
Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	München Klinik Schwabing	München		Germany

Investigators

Principal Investigator: Uta Behrends, München Klinik Schwabing

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Technical University of Munich

ClinicalTrials.gov Identifier:

NCT05638724

Other Study ID Numbers:

MLC-R Study

First Posted:

Dec 6, 2022

Last Update Posted:

Dec 14, 2022

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD: