# SARS-COV-2 causes significant abnormalities in the fibrinolysis system of patients: correlation between viral mutations, variants and thrombosis

**Authors:** Esra’a Abudouleh, Tarek Owaidah, Fatimah Alhamlan, Arwa A. Al-Qahtani, Reem M. Aljowaie, Fatimah Al-Ghnnam, Marie Fe Bohol, Ahmed A. Al-Qahtani

PMC · DOI: 10.3389/fcimb.2025.1531412 · Frontiers in Cellular and Infection Microbiology · 2025-04-15

## TL;DR

This study finds that specific SARS-CoV-2 mutations are linked to blood clotting issues and ICU admissions in COVID-19 patients.

## Contribution

The study identifies specific viral mutations and variants correlated with fibrinolysis abnormalities and thrombosis in severe cases.

## Key findings

- SARS-CoV-2 mutations like N501Y and Omicron BA.1.1 are linked to higher ICU admissions and thrombosis.
- tPA, aPTT, and D-dimer levels are elevated in patients with the N501Y mutation.
- Thrombosis is most common in severe cases, especially among unvaccinated individuals with comorbidities.

## Abstract

Coronavirus disease (COVID-19) is reported as a complex disorder affecting multiple systems and coagulopathy that can cause mortality. In this study, we investigated the correlation of SARS-CoV-2 mutations found in blood samples with various changes in the fibrinolysis system, as well as the severity of the disease based on outcome and whether or not these patients were admitted into the ICU.

COVID-19 patients (n = 446) admitted to our institute between 2021 and 2022 were recruited. Blood samples were collected, and a sequence analysis of the SARS-CoV-2 spike gene was isolated from the blood. Measured several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, and fibrinogen levels.

SARS-CoV-2 RNA was found in 123/446 (27.6%) of the blood samples. The N501Y, D614G, K417N, and P681R mutations among COVID-19 patients were associated with higher admissions to the ICU (P = 0.0057, P = 0.0068, P = 0.0193, and P = 0.018, respectively). Omicron (BA.1.1) variant variants are highly associated with thrombosis (P = 0.002) in hospitalized COVID-19 patients that are unvaccinated and have comorbidity conditions. The plasma levels of tPA, aPTT, and D-dimer were significantly higher in participants who had the N501Y mutation (P = 0.044, P = 0.024, and P = 0.027, respectively).

Thrombosis was the most prevalent condition among severe COVID-19 patients. The correlation between specific SARS-CoV-2 new variants and thrombosis warrants more investigation.

## Linked entities

- **Proteins:** SERPINF2 (serpin family F member 2), LOC125948914 (serine protease snake-like), CPB2 (carboxypeptidase B2), PLAT (plasminogen activator, tissue type), SERPINE1 (serpin family E member 1)
- **Diseases:** thrombosis (MONDO:0000831), coagulopathy (MONDO:0001531)

## Full-text entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, CPB2 (carboxypeptidase B2) [NCBI Gene 1361] {aka CPU, PCPB, TAFI}, SERPINF2 (serpin family F member 2) [NCBI Gene 5345] {aka A2AP, AAP, ALPHA-2-PI, API, PLI, alpha2AP}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}
- **Diseases:** Thrombosis (MESH:D013927), COVID-19 (MESH:D000086382), coagulopathy (MESH:D001778), Coronavirus disease (MESH:D018352)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** K417N, N501Y, D614G, P681R

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12037514/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12037514/full.md

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Source: https://tomesphere.com/paper/PMC12037514