Study Stopped
Grant application to fund this work was not funded. We won't be posting data for this study.
Understanding Immunology and Patient Outcomes of COVID-19 in Hospitalized Patients
1 other identifier
observational
16
1 country
1
Brief Summary
The adaptive immune response, consisting of antiviral T and B cells, is critical for providing protection against viruses such as SARS-CoV-2, both during an active infection and later following a subsequent exposure. They can both also potentially contribute to pathogenesis if they are overstimulated. Despite these advances in knowledge, there are still significant gaps in understanding of what constitutes a protective or immunopathologic immune response and its durability. Significant knowledge gaps also remain pertaining to the early recognition of COVID patients with increased risk of clinical deterioration who require continued hospitalization and the use of more intensive treatments designed to improve outcomes. Data from non-COVID patients with MI show that platelet surface expression of FcγRIIa, the low-affinity receptor for the Fc fragment of immunoglobulin (Ig) G, identifies patients at high and low risk of subsequent cardiovascular events. Platelet expression of FcγRIIa is increased by interferon γ20 that is significantly elevated in severe COVID-19 infections. The high prevalence of arterial thrombosis among COVID-19 patients and the central role of thrombosis in respiratory failure support the hypothesis that elevated platelet expression of FcγRIIa will identify COVID patients at increased risk of thrombotic complications and clinical deterioration. In addition to the potential role of platelet activation in thrombosis associated with COIVD-19, the endothelium may also play a significant role. The investigators hypothesize that elevated EMPs in plasma will identify patients at high risk of thrombosis and clinical deterioration. To begin to address the knowledge gaps above and obtain preliminary data for future large grant submission, the investigators propose a small, prospective, single-center cohort study that will enroll patients hospitalized for COVID-19 infection and exhibiting a range of disease severity. Biosamples will be obtained and used to study T and B cells, antibody repertoire, and durability of protective immunity, and also to quantify platelet expression of FcγRIIa and circulating EMPs, as described in the protocol.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Feb 2021
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 3, 2021
CompletedFirst Submitted
Initial submission to the registry
February 9, 2021
CompletedFirst Posted
Study publicly available on registry
May 19, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2023
CompletedMay 14, 2025
February 1, 2025
2.4 years
February 9, 2021
May 9, 2025
Conditions
Outcome Measures
Primary Outcomes (14)
To compare the polyfunctionality and frequency of antiviral CD4 and CD8 T cells.
The investigators hypothesize patients with severe disease will have higher frequencies of antiviral T cells that contribute to the cytokine storm observed in the most severe cases of COVID-19.
Four weeks (while hospitalized)
To compare the polyfunctionality and frequency of antiviral CD4 and CD8 T cells.
The investigators hypothesize patients with severe disease will have higher frequencies of antiviral T cells that contribute to the cytokine storm observed in the most severe cases of COVID-19.
12 months after hospital admission
To compare the frequency of plasmablasts (early B cells that produce antiviral antibodies) and plasma antiviral antibody titer during acute infection.
The investigators predict that patients with severe disease will have greater numbers of antiviral plasmablasts and plasma antiviral antibody levels compared to those with mild disease.
Four weeks (while hospitalized)
To compare the frequency of plasmablasts (early B cells that produce antiviral antibodies) and plasma antiviral antibody titer during acute infection.
The investigators predict that patients with severe disease will have greater numbers of antiviral plasmablasts and plasma antiviral antibody levels compared to those with mild disease.
12 months after hospital admission
The number of virus specific CD4 T cells will be measured using flow cytometry.
The investigators hypothesize that severe disease will result in the formation of higher magnitude antiviral B and T cell CHRMS (Medical) #STUDY00001369 Approved: 1/25/2021 4Human subjects protocol form 7/19/19responses during acute disease due to increased viral load and antigen in these patients. The investigators further predict that higher frequency T and B cells during acute disease will correlate with more robust durability of these responses during convalescence.
Four weeks (while hospitalized)
The number of virus specific CD8 T cells will be measured using flow cytometry.
The investigators hypothesize that severe disease will result in the formation of higher magnitude antiviral B and T cell CHRMS (Medical) #STUDY00001369 Approved: 1/25/2021 4Human subjects protocol form 7/19/19responses during acute disease due to increased viral load and antigen in these patients. The investigators further predict that higher frequency T and B cells during acute disease will correlate with more robust durability of these responses during convalescence.
Four weeks (while hospitalized)
The number of virus specific CD4 T cells will be measured using flow cytometry.
The investigators hypothesize that severe disease will result in the formation of higher magnitude antiviral B and T cell CHRMS (Medical) #STUDY00001369 Approved: 1/25/2021 4 Human subjects protocol form 7/19/19 responses during acute disease due to increased viral load and antigen in these patients. The investigators further predict that higher frequency T and B cells during acute disease will correlate with more robust durability of these responses during convalescence.
12 months after hospital admission
The number of virus specific CD8 T cells will be measured using flow cytometry.
The investigators hypothesize that severe disease will result in the formation of higher magnitude antiviral B and T cell CHRMS (Medical) #STUDY00001369 Approved: 1/25/2021 4Human subjects protocol form 7/19/19responses during acute disease due to increased viral load and antigen in these patients. The investigators further predict that higher frequency T and B cells during acute disease will correlate with more robust durability of these responses during convalescence.
12 months after hospital admission
To obtain preliminary data on platelet activation in patients hospitalized with COVID-19
To compare platelet activation, measured by platelet surface FcγRIIa while in hospital and 12 months after infection, in patients with severe (i.e., mechanical ventilation in ICU) vs. non-severe (hospitalized, but not in an ICU) COVID-19 disease.
Four weeks (while hospitalized)
To obtain preliminary data on platelet activation in patients hospitalized with COVID-19
To compare platelet activation, measured by platelet surface FcγRIIa while in hospital and 12 months after infection, in patients with severe (i.e., mechanical ventilation in ICU) vs. non-severe (hospitalized, but not in an ICU) COVID-19 disease.
12 months after hospital admission
To obtain preliminary data on endothelial activation in patients hospitalized with COVID-19
To compare endothelial activation, measured by circulating EMPs while in hospital and 12 months after infection, in patients with severe (i.e., mechanical ventilation in ICU) vs. non-severe (hospitalized, but not in an ICU) COVID-19 disease.
Four weeks (while hospitalized)
To obtain preliminary data on endothelial activation in patients hospitalized with COVID-19
To compare endothelial activation, measured by circulating EMPs while in hospital and 12 months after infection, in patients with severe (i.e., mechanical ventilation in ICU) vs. non-severe (hospitalized, but not in an ICU) COVID-19 disease.
12 months after hospital admission
Preliminarily determine if the FcγRIIa and EMPs have utility as biomarkers
To preliminarily determine if the FcγRIIa and EMPs have utility as biomarkers for prediction of thrombotic events and clinical deterioration in hospitalized patients with COVID-19.
Four weeks (while hospitalized)
Preliminarily determine if the FcγRIIa and EMPs have utility as biomarkers
To preliminarily determine if the FcγRIIa and EMPs have utility as biomarkers for prediction of thrombotic events and clinical deterioration in hospitalized patients with COVID-19.
12 months after hospital admission
Study Arms (1)
Covid-19+
Hospitalized patients with Covid-19 infection confirmed by PCR test
Interventions
Eligibility Criteria
This study will enroll patients hospitalized at the University of Vermont Medical Center who have a positive test result for COVID-19. These patients are expected to have a greater acuity of illness and burden of disease based on the fact that they require inpatient care. Enrolling hospitalized patients ensures a greater opportunity to collect serial biological specimens over the course of the illness due to the proximity of the patient to medical and research staff and UVM laboratories.
You may qualify if:
- Adult (≥18 years old) at the time of consent
- Positive COVID-19 PCR test result
You may not qualify if:
- Expected death or withdrawal of life-sustaining treatments within 3 days
- Hemoglobin ≤7.0 at the time of consent
- Unable to provide consent and no legally authorized representative (LAR) identified or reached by phone
- Pregnant
- Incarcerated
- Physician declines patient enrollment (attending physician or study physician)
- Patient or LAR do not consent to participate in the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Vermont
Burlington, Vermont, 05405, United States
Biospecimen
blood, nasal swabs
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Renee Stapleton, MD, PhD
University of Vermont
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Medicine
Study Record Dates
First Submitted
February 9, 2021
First Posted
May 19, 2021
Study Start
February 3, 2021
Primary Completion
June 30, 2023
Study Completion
June 30, 2023
Last Updated
May 14, 2025
Record last verified: 2025-02