Scope: Covid 19: Researching COVID To Enhance Recovery: IDeA States COnsortium for clinical REsearch (ISCORE) Network

Grants and Contracts Details

Description

CICN Site at UK: Coagulation and IgG Responses in Acute and Long COVID-19 Patients The scientific goals of the University of Kentucky (UK) CICN site are to understand the dysfunction in hemostasis/thrombosis occurring in acute and long COVID-19 patients and to define the immune responses to both primary infection and vaccines. In our ongoing longitudinal study, we are recruiting ICU and hospitalized inpatients, ambulatory outpatients, and healthy controls from central, northern, and eastern KY, including the underserved Appalachian region. In the first year of the pandemic, our hospital admitted 1,033 unique patients requiring at least supplemental O2. Our center has facilitated over 109,000 tests (as of 3/15/21). We expect to recruit and analyze, in detail, 200 SARS-CoV2+ patients/year in Aim 1 and more for serology in Aim 2. Based on our present data, 24% will be long COVID-19 patients. Our data show dysregulation in the coagulation system of COVID-19 patients and significant variations in anti-viral IgGs. These data justify our two specific aims. In addition to these Aims, we will provide appropriate samples and patient data to the greater CICN consortium. Aim 1: Define the alterations in hemostatic systems occurring in Acute and Long COVID-19 patients. We hypothesize that immune cells involved in anti- SARS-CoV-2 responses affect coagulation factors and/or platelets to increase occlusive thrombotic risk. From our preliminary data, plasmas from hospitalized patients have increased thrombin generation potential, decreased anticoagulant Protein S (PS) (Fig. A), increased procoagulant von Willebrand Factor (vWF) (Fig. B), and increased complement activation (Fig. C). Platelets from the same patients show modest activation as measured by flow cytometry of platelet- leukocyte aggregates and morphological changes. Expression of Tissue Factor (TF), an initiator of coagulation, is higher on activated monocytes from inpatients, suggesting that virus-reacting monocytes may trigger the coagulation cascade. To define alterations in hemostatic systems, we will measure PS, VWF, and activated complement factor c5 by ELISA; plasma thrombin generation by thrombography; and platelet, lymphocyte, and immune cell (monocyte, macrophage, T cells) phenotypes, such as TF expression, using the Flow Cytometry and Immune Monitoring Core at UK. These metrics will be correlated with EMR data. Aim 2: Determine underlying conditions that affect SARS CoV2 vaccine immune responses. In preliminary studies, 2/2 transplant patients on immunosuppression, lacked detectable anti-spike (S) IgG/M despite two vaccinations; 10/10 controls had anti-S IgG (Fig. D). Socio-economic and medical factors (i.e., cancer, diabetes/obesity, depression) can confound vaccination efficacy resulting in low anti-SARS-CoV-2 IgG. These confounders are prevalent in Kentucky, particularly Appalachia. We hypothesize that conditions, known to affect immune systems, will reduce vaccine efficacy. We also hypothesize that patients with long COVID will have immune deficits that reduce responses to infection and/or vaccination. To test these, we will use serology of plasmas and a validated at-home blood collection kit (Mitra, Fig. E) to measure Ig responses in recruited patients. Measurements will use ELISAs against S and N protein (N protein activity distinguishes COVID-induced responses). Results will be correlated with the medical and socio-economic conditions of the subjects. Patient Recruitment: Of the 25 poorest US counties, Appalachian KY has 10. This region is overwhelmingly rural and isolated. We will leverage longstanding regional engagement infrastructure (Center for Excellence in Rural Health) and partner with community-based organizations, community health workers, and local health care providers to recruit patients from this population. Our post-ICU clinic will also be a source of patients as will our Infectious Disease Clinic. We have created a research registry for COVID-19 patients allowing patients to self- refer via link or QR code posted in high traffic areas. Wild Health, who conducts much of the regional testing, will add this link to every result sent. All respondents will receive a health survey. We will recruit adults that demographically reflect our population: 10% African American, 3% Hispanic, 1% Asian, and 1% Native American. Patients will be screened with a HIPAA Waiver of Authorization form, approved as per IRB protocols. Enrollment is complete following consent either electronically via a secured RedCAP system or in person. Data will be extracted from EMRs to correlate with clinical parameters at the time of the research blood draw.
StatusFinished
Effective start/end date10/1/219/16/22

Funding

  • West Virginia University

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