VEGF and sFlt-1 Levels in the Pathogenesis and Severity of COVID-19 Disease

COVID-19 RELATED SUBMISSION: VEGF and sFlt-1 Levels in the Pathogenesis and Severity of COVID-19 Disease

To assess blood levels of vasoactive mediators that may regulate pulmonary endothelial permeability and contribute to multi-organ injury in patients with COVID-19 disease and to correlate the levels of these mediators with disease outcomes such as ICU admission, length of ventilatory support, respiratory failure, kidney failure, heart failure, and death.

Study Overview

• Status: Completed
• Conditions: COVID-19 Disease

Detailed Description

When patients are sick with other lung infections (pneumonias) caused by viruses or bacteria there are changes in a pathway that regulates the "leakiness" the tiny airspaces inside the lungs. Even bigger changes in this pathway are seen when patients develop severe breathing difficulties (acute respiratory distress syndrome) similar to what is seen in patients who get really sick with COVID-19 disease.

There are important changes in this pathway that occur in patients who have preexisting cardiovascular (heart) disease who do not have lung infections. The investigator will evaluate these levels in patients with COVID-19 because the investigator believes that this baseline difference in pathway regulation may be one reason patients with heart disease who contract COVID-19 get sicker than patients without heart or vascular disease.

The investigator will also assess the levels of components of this pathway in patients who are less sick with those who became sick enough to require a tube to help them breathe because this is important to determine if COVID-19 lung disease has a similar effect on this pathway as other lung infections like flu and bacterial pneumonias.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients who have available specimens in the UAB CCTS Biorepository for COVID-19 patients. (IRB-300005127: COVID-19 Enterprise Biorepository.)

Description

Inclusion Criteria:

• Positive test for COVID-19 (SARS-CoV-2 infection)
• >=18 years
• Blood (plasma) specimen(s) available in the CCTS biorepository

Exclusion Criteria:

• <18 years
• Lack of blood specimen

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Group 1: Group 1: COVID-19 + inpatients who did not require mechanical ventilation (25 patients);
Group 2: Group 2: COVID-19 + inpatients who required mechanical ventilation (25 patients).
Group 3: Group 3: COVID-19 + inpatients with no preexisting cardiovascular disease (25 patients)
Group 4: Group 4: COVID-19 + inpatients with preexisting cardiovascular disease (25 patients).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory Assays	The primary outcome measure is the ratio of soluble fms-like tyrosine kinase receptor-1 (sFlt-1) to vascular endothelial growth factor (VEGF) which will be obtained using an immunoassay on blood samples. The specimens will be analyzed using enzyme-linked immunosorbent assay and reported as a ratio	7-14 days after symptom onset
VEGF-A	Plasma samples will be analyzed to measure VEGF-A	7-14 days after symptom onset
VEGF-C	Plasma samples will be analyzed to measure VEGF-C	7-14 days after symptom onset
VEGF-D	Plasma samples will be analyzed to measure VEGF-D	7-14 days after symptom onset
Tie-2	Plasma samples will be analyzed to measure Tie-2	7-14 days after symptom onset
Flt-1	Plasma samples will be analyzed to measure Flt-1	7-14 days after symptom onset
PlGF	Plasma samples will be analyzed to measure PlGF	7-14 days after symptom onset
FGF	Plasma samples will be analyzed to measure FGF	7-14 days after symptom onset

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Dylan Addis, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Actual): October 6, 2025
• Study Completion (Actual): October 6, 2025

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; SARS-CoV-2 viral infection; VEGF and sFlt-1 levels
• Additional Relevant MeSH Terms: 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
• Other Study ID Numbers: IRB-300005378; UAB (Other Identifier: UAB)

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