# Cellular effects of SARS-CoV-2 in mediating thrombotic susceptibility

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $673,720

## Abstract

Project Summary
Infection with severe acute respiratory syndrome novel corona virus (SARS-CoV-2) causes COVID-19. In
severe cases, COVID-19 leads to profound inflammation (“cytokine storm”) followed by coagulopathy and a
prothrombotic-state with progression to multiple organ failure. Several cytokines, including IL6 are elevated.
Further, a proinflammatory galectin, Galectin-3 (Gal-3) is also found elevated. Gal-3 upregulates IL6 and other
cytokines, can directly activate platelets, neutrophils, and endothelial cells, and is known to mediate venous
thrombosis via IL6 in a mouse model. A growing body of literature has implicated neutrophil, platelet and
endothelial cell activation as potential drivers of thrombotic complications in COVID-19 patients. However,
there are no direct mechanistic links established between inflammation, vascular cell activation, and
thrombosis during SARS-CoV-2 infection. Our objective is to define the mediators that cause activation of
neutrophils, platelets and/or endothelial cells during SARS-CoV-2 infection and their mechanistic roles in
promoting thrombin generation and thrombosis. At the University of Iowa, we led a multicenter randomized
clinical trial (RCT) comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized
patients with COVID-19 (NCT04360824) and collected plasma samples for biomarkers and mechanistic
studies. Given the upsurge in late thrombotic complications of COVID-19, we now propose to recruit additional
patients to collect serial samples every week during hospitalization and thereafter every 3 months for up to 3
years. We hypothesize that thrombogenicity in COVID-19 is mediated by IL6- and Gal-3-driven activation of
hematopoietic and endothelial cells and that the prothrombotic state persists even after recovery from viral
infection. Our team has a unique combination of expertise and resources that will address the hypothesis in 2
well integrated but independent aims. In Aim 1, using serially collected patient’s samples, we will determine
the mechanistic role of IL6, Gal-3, and NETs in mediating cellular activation and enhancing thrombin
generation and thrombosis in COVID-19. Aim 2 will utilize a novel transgenic mouse model of SARS-CoV-2
infection to determine if targeting IL6, Gal-3, or NETs in vivo protects against cellular activation, thrombin
generation and thrombosis. A strength of this proposal is in utilizing clinical samples and a novel preclinical
model to identify critical mechanistic pathways for cellular activation, thrombin generation and in vivo
thrombosis in COVID-19. Thus, the overall impact of the proposed research agenda is very high and is likely to
provide therapeutic targets for decreasing thrombotic burden in COVID-19.

## Key facts

- **NIH application ID:** 10467274
- **Project number:** 1R01AI162778-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Sanjana Dayal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $673,720
- **Award type:** 1
- **Project period:** 2022-02-09 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467274

## Citation

> US National Institutes of Health, RePORTER application 10467274, Cellular effects of SARS-CoV-2 in mediating thrombotic susceptibility (1R01AI162778-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467274. Licensed CC0.

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