Post-acute COVID-19 Sequelae in Denmark

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

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, 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

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Non-communicable Disease
• Intervention / Treatment: Procedure: blood sample; Other: Online questionaire

Detailed 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. The study aims to investigate the hypothesis that biomarkers can predict if SARS-CoV-2 infection leads to increased and exacerbated non-communicable pulmonary, cardiovascular, and renal diseases.

Further, we address the unmet need to understand the molecular mechanisms responsible for the link between post-acute effects of SARS-CoV-2 and complications in the pulmonary, cardiovascular, and renal system. More specific we will investigate the molecular mechanisms responsible for the aetiology and decline in organ function.

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.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Ove Andersen, Professor; Phone Number: +4529333262; Email: ove.andersen@regionh.dk
• Study Contact Backup: Name: Mette Bendtz Lindstroem, MPH; Phone Number: +4538623308; Email: mlin0062@regionh.dk

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Copenhagen University Hospital, Amager and Hvidovre
    • Contact: Ove Andersen, Professor; Phone Number: +4529333262; Email: ove.andersen@regionh.dk
    • Contact: Mette Lindstroem, MPH; Phone Number: +4538623308; Email: mlin0062@regionh.dk
    • Contact: Ove Andersen, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The participating patients are former patients admitted to Hvidovre Hospital with the diagnosis OBS-COVID

Description

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
• Patients who do not understand or speak Danish

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SARS-CoV-2 positive patients; a cohort of former patients hospitalized with COVID-19	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.
SARS-CoV-2 negative patients; a control group of former patients hospitalized with other respiratory diseases	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.Is there a difference in the incidence and disease progression of NCD (pulmonary, cardiovascular, and renal disease) in the PAP between SARS-CoV-2-positive patients and a control group of patients admitted with other respiratory diseases?	Primary outcomes: Incidence of incipient NCD; Change in health-state of pre-existing NCD	Follow-up from index-admission to March 1, 2026
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 a control group of patients admitted with other respiratory diseases?	• Level in admission biomarkers associated with incipient or worsening of NCD in PAP	Follow-up from index-admission to March 1, 2026
3. Which biomarkers are involved in development or disease progression of NCDs in PAP?	Principal outcomes: Identify in vivo biomarkers in admission and follow-up blood samples associated with tissue /organ damage, and inflammation; Investigate in vitro molecular mechanisms in follow-up blood samples by examining cellular morphology, metabolism, stress response, fibrosis, viability, proliferation, senescence, and inflammation.	Follow-up from index-admission to March 1, 2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.Is there a difference in the incidence and disease progression of NCD (pulmonary, cardiovascular, and renal disease) in the PAP between SARS-CoV-2-positive patients and a control group of patients admitted with other respiratory diseases?	Other outcomes: Incidence of incipient NCD stratified by the socioeconomic position of patients; Change in health-state of pre-existing NCD stratified by the socioeconomic position of patients	Follow-up from index-admission to March 1, 2026
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 a control group of patients admitted with other respiratory diseases?	• Level in admission biomarkers associated with symptoms, lower quality of life, functional impairment in PAP.	Follow-up from index-admission to March 1, 2026

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Investigators: Principal Investigator: Ove Andersen, Professor, Department of Clinical Research, Copenhagen University Hospital, Hvidovre; Study Chair: Jon Ambaek Durhuus, PhD, Department of Clinical Research, Copenhagen University Hospital, Hvidovre

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Ageing; Sequelae; Non-communicable disease
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Noncommunicable Diseases
• Other Study ID Numbers: H-24039578

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Only aggregated data can be available for other researchers due to Danish Data Protection Law

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No