Post-acute COVID-19 Sequelae in Denmark

COVID-19 Clinical Trial

Official title:

Investigation of COVID-19 Post-acute Sequelae in Patients From Hvidovre Hospitals Catchment Area, and in a Register of the Danish Population 2000-2026

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06191302
• Other study ID #: H-23072177
• Status: Not yet recruiting
• Start date: February 1, 2024
• Est. completion date: March 1, 2026

Study information

• Verified date: January 2024
• Source: Hvidovre University Hospital
• Contact: Ove Andersen, Professor
• Phone: +4529333262
• Email: ove.andersen[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Since the first SARS-CoV-2 cases in 2019, over 660 million COVID-19 cases have been reported globally, including 183 million in the EU. Up to 70% of those infected experience reduced organ function four months or more after a COVID-19 diagnosis, potentially increasing the risk of non-communicable diseases (NCDs). The post-acute phase (PAP) after COVID-19 (four months or more after the acute phase) can lead to impaired function in various organ systems, with a focus on the lungs, cardiovascular system, and kidneys. These three NCDs collectively impose a significant burden on individuals and society. Urgently, we need to understand the connection between COVID-19's PAP and NCDs, identifying robust biomarkers for early detection. This study examines PAP and associated risk factors, investigating the link between PAP and the heightened risk of lung, heart, and kidney complications. Utilizing data from a cohort of COVID-19 patients and a control group with respiratory diseases, the study aims to determine prevalence and risk ratios more precisely. The aim is to contribute to minimizing the risk of NCD development or exacerbation in current and future COVID-19 patients, enhancing our understanding of chronic disease development at the population leve

Description:

The post-acute phase (PAP) after COVID-19 (four months or more after the acute phase of COVID-19) can manifest with reduced function in multiple organ systems, with a particular focus on the lungs, cardiovascular system, and kidneys. Collectively, these three non-communicable diseases (NCDs) represent a significant burden for both the individual and society as a whole. There is an urgent need to elucidate this connection and build a more detailed understanding of the link between COVID-19's PAP and individual NCDs, as well as to identify robust biomarkers that can assist in the early identification of the development of these NCDs.

This study focuses on PAP and the associated risk factors in this later phase of the disease, examining the relationship between PAP and the increased risk of specifically lung, heart, and kidney complications in the Danish population. Additionally, data (medical records, registry data, patient reported outcomes and blood samples) from a cohort of former patients hospitalized with COVID-19, as well as a control group hospitalized with other respiratory diseases, are investigated to determine the prevalence and risk ratios in disease development more precisely.

The purpose of the study is to contribute to minimizing the risk of developing or worsening NCDs in current and future COVID-19 patients, as well as contributing to our understanding of chronic disease development at the population level. We will identify molecular mechanisms for PAP after COVID-19, examining whether there are biomarkers that can be used for early risk assessment and provide information about disease progression. Furthermore, the project has the potential to contribute to the discovery of new drugs that can reduce the risk associated with PAP after COVID-19, as data from the project will be used in the construction of a trans-European simulation model for virtual drug testing ("virtual twin").

The population in the registry study is the entire population of Denmark. The population in the clinical cohort consists of former patients who have been admitted to Hvidovre Hospital with the diagnosis OBS COVID. Participants consent to the use of residual material from their blood sample, taken during their hospitalization with the diagnosis OBS-COVID in the period 2020-2022 (index blood sample). After obtaining consent, patients come to Hvidovre Hospital, where a blood sample (follow-up blood sample) is taken, and an online questionnaire is completed and stored in REDCap. Blood samples are analyzed and compared with collected registry data and questionnaire data, after which the results are reported in international peer-reviewed journals.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 800
• Est. completion date: March 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a blood sample in the clinical biobank related to the OBS-COVID index admission

• Aged above 18 years at time of index-admission

Exclusion Criteria:

• Patients without a Danish personal identification number

• Terminal patients

• Patients who do not understand or speak Danish

Related Conditions & MeSH terms

• COVID-19
• Non-communicable Disease
• Noncommunicable Diseases

Intervention

Procedure:
• blood sample
Blood sample collected in the post-acute period (follow-up visit) will be analysed for biomarkers predictive for diseases related to and disease progression in various organ systems (e.g., cardiovascular, pulmonary, and renal systems), including e.g., Pro-BNP, NGAL, and interleukins.

Other:
• Online questionaire
The participants will complete an online questionnaire related to disease and health issues associated with COVID-19 and COVID-19 post-acute sequalae's and existing Non-Communicable Disease.

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital, Amager and Hvidovre	Hvidovre

Sponsors (1)

Lead Sponsor	Collaborator
Hvidovre University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1.1: Research question: Do pre-existing chronic conditions (e.g., chronic obstructive pulmonary disease (COPD), diabetes, and ischemic heart disease) affect the incidence and progression of new NCD and progression of pre-existing NCD in the PAP?	Assess the association between SARS-CoV-2 infection and incidence or exacerbation of NCD, by determining differences in the incidence of comorbidities (e.g., COPD, diabetes, and ischemic heart disease) and in the incidence and severity of NCD (e.g., pulmonary, cardiovascular, and renal disease) among SARS-CoV-2 infected and not infected individuals.	Follow-up from index-admission to March 1, 2026
Primary	1.2 Research question: Do the different SARS-CoV-2 strains affect the incidence and progression of new NCD and progression of pre-existing NCD in the PAP?	Determine the relationship between strains and incidence or exacerbation of NCD (e.g., pulmonary, cardiovascular, and renal disease).	Follow-up from index-admission to March 1, 2026
Primary	1.3 Research question: Do sex and/or SES affect the incidence or exacerbation of NCD after SARS-CoV-2 infection?	Examine associations of SES and sex with NCD incidence/severity, using SES indicators such as income, education, occupation, employment, ethnicity, public benefits and NCD incidence/severity indicators	Follow-up from index-admission to March 1, 2026
Primary	2.1 Research question: Are there differences in the distribution of biomarkers and clinical characteristics at admission between SARS-CoV-2 positive patients and patients admitted with other respiratory diseases and other respiratory symptoms?	Examine the association and difference in biomarker levels (e.g., inflammatory markers, cytokines, organ- and disease-specific markers) and clinical characteristics in COVID-19-positive patients compared to COVID-19-negative patients.	First 6-hours of index-hospitalization
Primary	2.2 Is there a difference in the association of admission biomarkers and incidence, severity, and disease progression of NCD in PAP, between SARS-CoV-2 positive patients and patients admitted with other respiratory disease/symptoms?	Assess the association between measured biomarkers and the occurrence, severity, or types of NCD (e.g., pulmonary, cardiovascular, and renal disease)	Follow-up from index-admission to March 1, 2026
Primary	2.3 Research question: Does SARS-CoV-2 infection modify the in-hospital disease progression of pre-existing conditions (e.g., COPD, diabetes, and ischemic heart diseases)?	Medicine, interventions, and biomarkers related to acute disease progression as well as standard blood biomarkers (e.g., soluble urokinase plasminogen activator receptor (suPAR), lactate dehydrogenase, leukocytes, albumin, C-reactive protein (CRP), blood urea nitrogen, glomerular filtration rate)	Follow-up from admission to discharge at index-hospitalization
Primary	3.1 Research question: Is there a difference in the prevalence and symptom burden of NCD in the PAP between SARS-CoV-2 -positive patients and patients admitted with other respiratory diseases and other respiratory symptoms?	Assess and analyse patient-reported outcomes (e.g., perceived symptom severity, quality of life, and functional impairment)	Follow-up from index-admission to March 1, 2026
Primary	3.2 Research question: Is the association between pre-existing conditions and NCD-related outcomes modified by the post-acute SARS-CoV-2 status?	Examine if pre-existing conditions predispose post-acute COVID-19 individuals to increased/exacerbated NCD by delineate associations.	Follow-up from index-admission to March 1, 2026
Primary	4.1 Research question: Can cell-free plasma or serum from individuals with post-acute COVID-19 and NCD affect the fitness of a cell culture, and which circulating biomarkers are involved?	In cell culture, examine cellular fitness (e.g., morphology, bioenergetics (metabolism), stress response, fibrosis, viability/proliferation, senescence, and inflammation).	Feb 1, 2024 to Jan 31, 2028
Primary	4.2 Research question: Can circulating biomarkers found in 4.1 be used to describe the risk or progression of NCD?	Identify biomarkers and investigate biomarker-NCD associations	Feb 1, 2024 to Jan 31, 2028
Secondary	1.1: Research question: Do pre-existing chronic conditions (e.g., chronic obstructive pulmonary disease (COPD), diabetes, and ischemic heart disease) affect the incidence and progression of new NCD and progression of pre-existing NCD in the PAP?	Length of hospitalization (LOS), all-cause mortality, severity of COVID-19 symptoms in individuals with comorbidities, COVID-19 complications (e.g., pneumonia) in individuals with comorbidities, vaccine effectiveness, after-COVID-19 symptoms and quality of life, and severity grading of NCD.	Follow-up from index-admission to March 1, 2026
Secondary	1.2 Do the different SARS-CoV-2 strains affect the incidence and progression of new NCD and progression of pre-existing NCD in the PAP?	Distribution of SARS-CoV-2 types. Determine differences in the LOS, mortality rate, complications, interventions, pharmacological treatment, and vaccine effectiveness in groups infected with different strains.	Follow-up from index-admission to March 1, 2026
Secondary	1.3 Research question: Do sex and/or SES affect the incidence or exacerbation of NCD after SARS-CoV-2 infection?	LOS, all-cause mortality, severity of COVID-19 symptoms in individuals with comorbidities, COVID-19 complications, vaccination status, and sick leave.	Follow-up from index-admission to March 1, 2026
Secondary	2.1 Research question: Are there differences in the distribution of biomarkers and clinical characteristics at admission between SARS-CoV-2 positive patients and patients admitted with other respiratory diseases and other respiratory symptoms?	All-cause mortality, LOS, inpatient disease progression (e.g., ICU, invasive mechanical ventilation, treatment response, and biomarker dynamics/profiles).	First 6-hours of index-hospitalization
Secondary	2.2 Is there a difference in the association of admission biomarkers and incidence, severity, and disease progression of NCD in PAP, between SARS-CoV-2 positive patients and patients admitted with other respiratory disease/symptoms?	Predictive values of measured biomarkers and biomarker patterns compared to LOS, risk of inpatient disease progression, after-COVID symptoms, and quality of life.	Follow-up from index-admission to March 1, 2026
Secondary	2.3 Research question: Does SARS-CoV-2 infection modify the in-hospital disease progression of pre-existing conditions (e.g., COPD, diabetes, and ischemic heart diseases)?	Hospital admission, risk of inpatient disease progression.	Follow-up from admission to discharge at index-hospitalization
Secondary	3.1 Research question: Is there a difference in the prevalence and symptom burden of NCD in the PAP between SARS-CoV-2 -positive patients and patients admitted with other respiratory diseases and other respiratory symptoms?	Medicines, interventions, biomarkers related to biological ageing, acute disease progression as well as standard blood biomarkers (e.g., suPAR, lactate dehydrogenase, leukocytes, albumin, CRP, blood urea nitrogen, glomerular filtration rate)	Follow-up from index-admission to March 1, 2026
Secondary	3.2 Research question: Is the association between pre-existing conditions and NCD-related outcomes modified by the post-acute SARS-CoV-2 status?	Type of NCD, impact of pre-existing conditions on NCD recovery, mortality, and treatment response.	Follow-up from index-admission to March 1, 2026
Secondary	4.2 Research question: Can circulating biomarkers found in 4.1 be used to describe the risk or progression of NCD?	Virtual modelling of post infection NCD related to pulmonary, renal, and cardiovascular tissues.	Feb 1, 2024 to Jan 31, 2028