# Molecular pathogenesis of COVID-19-associated coagulopathy and new therapeutic approaches

> **NIH HL R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2026 · $695,610

## Abstract

Project Summary
Many studies have highlighted a large incidence of hemostatic derangements in the form of hypercoagulable
and hypofibrinolytic states following SARS-CoV-2 infection. These hemostatic disturbances are fueled by and a
consequence of the concomitant activation of the endothelium following a severe inflammatory response, with
likely contribution from many other pathways and components, such as the complement pathway and neutrophil
activation. In COVID-19 patients, the resulting hyperinflammation, vascular dysfunction, and systemic
hypercoagulability, collectively referred to as COVID-19-associated coagulopathy (CAC), manifests as the
increased tendency of micro-thrombosis of different organs leading to organ dysfunction, venous
thromboembolism, pulmonary embolism, and deep vein thrombosis. Reducing the deleterious impact of CAC
during severe SARS-CoV-2 infections continues to represent a major therapeutic challenge. Despite the
enormous effort exerted during the pandemic to understand the pathological mechanisms responsible for the
severity of SARS-CoV-2 infections, a major knowledge gap about the drivers and mechanisms underlying CAC
still exists. Furthermore, as the link between CAC and long COVID becomes more apparent, understanding CAC
is more urgent than ever. Proposed studies are designed to gain knowledge on the drivers and mechanisms
underlying CAC and will test the feasibility of several potential pharmacological approaches to blunt it. Levering
our novel and carefully optimized mouse model of COVID-19 and CAC, relying on a human pathological SARS-
CoV-2 strain and recapitulating major pathological alterations and development of CAC observed in human
patients presents a unique opportunity for hypotheses-driven research in a controlled and systematic manner to
gain important new insights on CAC. Mimicking worldwide observations that males are more susceptible to
severe disease after SARS-CoV-2 infection compared to females, a sex-dependent bias i

## Key facts

- **NIH application ID:** 11251250
- **Project number:** 5R01HL172048-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Roberto  Aiolfi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $695,610
- **Award type:** 5
- **Project period:** 2024-01-01T00:00:00 → 2028-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11251250

## Citation

> US National Institutes of Health, RePORTER application 11251250, Molecular pathogenesis of COVID-19-associated coagulopathy and new therapeutic approaches (5R01HL172048-03). Retrieved via AI Analytics 2026-07-16 from https://api.ai-analytics.org/grant/nih/11251250. Licensed CC0.

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