Semin Thromb Hemost 2022; 48(07): 858-868
DOI: 10.1055/s-0042-1756306
Review Article

Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness

Lize M. Grobbelaar
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
,
Arneaux Kruger
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
,
Chantelle Venter
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
,
Este M. Burger
2   BioCODE Technologies, Stellenbosch, South Africa
,
Gert J. Laubscher
3   Mediclinic Stellenbosch, Stellenbosch, South Africa
,
Tongai G. Maponga
4   Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa
,
Maritha J. Kotze
5   Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
,
Hau C. Kwaan
6   Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
,
Joseph B. Miller
7   Departments of Emergency Medicine and Internal Medicine, Henry Ford Hospital, Detroit, Michigan
,
Daniel Fulkerson
8   Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, Indiana
,
Wei Huff
8   Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, Indiana
,
Eric Chang
9   Indiana University School of Medicine - South Bend, Notre Dame, Indiana
,
Grant Wiarda
10   Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
,
Connor M. Bunch
7   Departments of Emergency Medicine and Internal Medicine, Henry Ford Hospital, Detroit, Michigan
,
Mark M. Walsh
9   Indiana University School of Medicine - South Bend, Notre Dame, Indiana
10   Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
11   Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
,
Syed Raza
12   Department of Critical Care Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
,
Mahmud Zamlut
12   Department of Critical Care Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
,
Hunter B. Moore
13   Division of Transplant Surgery, Department of Surgery, Denver Health and University of Colorado Health Sciences Center, Denver, Colorado
,
Ernest E. Moore
14   Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health and University of Colorado Health Sciences Center, Denver, Colorado
,
Matthew D. Neal
15   Pittsburgh Trauma Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
,
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
16   Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, England, United Kingdom
17   The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
,
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
17   The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
› Author Affiliations
Funding D.B.K.: Novo Nordisk Foundation for support (grant NNF20CC0035580). M.J.K. and T.G.M.: Research reported in this article was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation (Project Code 96825). E.P.: Laboratory research supported by NRF of South Africa (grant number 142142) and SA MRC (self-initiated research (SIR) grant). The content and findings reported and illustrated are the sole deduction, view, and responsibility of the researchers and do not reflect the official position and sentiments of the funders.

Abstract

Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with omicron variants are significantly raised over those of healthy, matched controls, they are raised to levels significantly lower than those seen with more severe variants such as beta and delta. We also observed that individuals infected with omicron variants manifested less extensive microclot formation in platelet-poor plasma compared with those harboring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of “internal control” that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots may play an important role in reflecting the severity of symptoms observed in COVID-19.

Ethics Statement

Ethical approval for blood collection and microclot analysis of blood samples from participants with COVID-19 and healthy individuals was given by the Health Research Ethics Committee (HREC) of Stellenbosch University (reference N19/03/043, project ID 9521; renewal 2021 and 2022). This laboratory study was performed in strict adherence to the International Declaration of Helsinki, South African Guidelines for Good Clinical Practice, and the South African Medical Research Council (SAMRC) Ethical Guidelines for research. Consent was obtained from all participants. A positive COVID-19 test was confirmed before blood collection. Genomic sequencing to confirm SARS-CoV-2 is covered under Health Research Ethics Committee (HREC) of Stellenbosch University (reference #N20/04/008_COVID-19) as part of the National Genomics Surveillance Program.




Publication History

Article published online:
29 September 2022

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