Coagulation Parameters in Post-Covid-19 Condition in Relation to Various Titers of Anti-SARS-CoV-2 IgG in Blood Plasma.

Background and Objectives: Post-COVID-19 condition is thought to affect 10-20% of people at least 3 months after a diagnosis of COVID-19 and two months of symptoms. Post-COVID-19 condition presents itself with many clinical effects with varying degrees of severity ranging from a mild cough to a life-threatening coagulopathy. Our study aimed to identify a relationship between the titers of anti-SARS-CoV-2 IgG and anticoagulation parameters: antithrombin III (ATIII), protein C (PC) and thrombomodulin (TM). Materials and Methods: Blood plasma was collected from healthy donors aged 25-45 who had recovered from COVID-19 3-6 months ago and their titers of anti-SARS-CoV-2 IgG and ATIII, PC, and TM were measured. Results: We found that concentrations and activities of key anticoagulation parameters (ATIII, PC, and TM) measured in donor plasma during the post-COVID-19 varied in relation to the titers of anti-SARS-CoV-2 IgG. Conclusion: While we identified a dysfunction of anticoagulation parameters in patients with post-COVID-19, we aim to explore the subpopulation antibody IgG fraction directly using in vivo and in vitro experiments with the possibility to contribute to the development of treatment options for post-COVID-19 conditions.

A study of fibrinolytic system components in donor groups depending on various titers of circulating anti-SARS-CoV-2 IgG in the bloodstream.

The fibrinolytic system plays an important role in controlling blood coagulation at each stage, from thrombin generation to fibrin clot cleavage. Currently, long-term multiorgan dysfunction post-coronavirus disease 2019 (COVID-19) may include coagulation disorders. Little information is available about the potential causes of post-COVID-19 coagulopathy, but one of them may be subpopulation IgG produced by the immune system against SARS-CoV-2. This article describes the changes in the main parameters of the fibrinolytic system in donors with various titers of anti-SARS-CoV-2 IgG, which is part of a complex study of the hemostasis system in these donor groups. We determined the most significant parameters of the fibrinolytic system, such as potential activity and amount of plasminogen and tissue plasminogen activator (tPA), amount of plasminogen activator inhibitor-1 (PAI-1), inhibitory potentials of α-2-antiplasmin, α-1-antitrypsin, α-2-macroglobulin in the blood plasma of donor groups. The obtained results represent the maximum and minimum values of measurement parameters among donor groups with titers of anti-SARS-CoV-2 IgG at least 10 ±â€Š3 Index (S/C), and their statistical differences from the reference point [donor group with titer of anti-SARS-CoV-2 IgG 0 Index (S/C)]. We established the changes in fibrinolytic parameters depending on the titers of anti-SARS-CoV-2 IgG. One conclusion can be drawn from this: anti-SARS-CoV-2 IgG population may influence coagulation in the post-COVID-19 period. Further research in-vitro and in-vivo experimental models using selected and purified IgG may confirm our previous findings.

Circulating levels of inflammatory cytokines and angiogenesis-related growth factors in patients with osteoarthritis after COVID-19.

Background: The disease COVID-19, caused by SARS-CoV-2 infection, has a systemic effect and is associated with a number of pathophysiological mechanisms that mobilize a wide range of biomolecules. Cytokines and growth factors (GFs) are critical regulators of tissue damage or repair in osteoarthritis (OA) and are being recognized as key players in the pathogenesis of COVID-19. A clear understanding of the long-term consequences of SARS-CoV-2 infection, especially in patients with concomitant chronic diseases, is limited and needs to be elucidated. The study aimed to evaluate the degree of inflammation and levels of pro-angiogenic and hypoxic factors, as well as heat shock proteins HSP60 and HSP70 in plasma, of patients with OA after recovery from COVID-19. Methods: The research involved patients of an orthopedic specialty clinic aged 39 to 80 diagnosed with knee OA. All examined patients were divided into three groups: the Control group included conditionally healthy donors, group OA included patients with knee OA mainly stage II or III and the group of OA and COVID-19 included patients with OA who had COVID-19. The plasma levels of pro-inflammatory molecules IL-1ß, IL-6, TNF-α, NF-κB, angiogenic factors VEGF, FGF-2, PDGF, hypoxic factor HIF-1α and molecular chaperones HSP60 and HSP70 were measured by enzyme-linked immunosorbent assay. Results: The study showed that in both groups of patients, with OA and convalescent COVID-19, there was an increase in the plasma level of IL-1ß and a decrease in TNF-α and NF-κB levels when compared to healthy controls. Systemic deregulation of the cytokine profile was accompanied by reduction in plasma levels of pro-angiogenic growth factors, most pronounced in cases of VEGF and PDGF. This analysis did not reveal any significant difference in the plasma level of HIF-1α. A decrease in the level of stress protein HSP60 in the blood of patients with OA, as well as those patients who have had SARS-CoV-2 infection, has been established. Conclusion: The results suggest the potential role pro-inflammatory cytokines and angiogenesis-related growth factors in pathogenesis of both joint pathologies and long-term systemic post-COVID-19 disorders.

Plasma Levels of MMPs and TIMP-1 in Patients with Osteoarthritis After Recovery from COVID-19.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. OBJECTIVE: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. METHODS: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. CONCLUSION: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

Characteristics of Products of Fibrinogen Origin in the Presence of Anti- SARS-CoV-2 IgG in the Bloodstream.

BACKGROUND: The hemostasis system has been extensively investigated in patients in the acute phase of coronavirus disease 2019 (COVID-19). In contrast, the post-COVID syndrome is a poorly known entity, and there is a lack of information on the mechanisms underlying the hemostasis abnormalities in the post-COVID period. AIM: To analyze the potential changes in the parameters of the hemostasis system in the post- COVID period in the plasma of donors with different titers of anti-SARS-CoV-2 IgG. METHODS: The plasma from 160 donors who had recovered from COVID infection was used in the study. Based on the results of the Abbott SARS-CoV-2 IgG serological assay, all donors were divided into several groups: 5 ± 3 (n = 20); 55 ± 5 (n = 20); 65 ± 5 (n = 20); 75 ± 5 (n = 20); 85 ± 5 (n = 20); 95 ± 5 (n = 20); 125 ± 5 (n = 20); 175 ± 5 (n = 20) Index (S/C). A total of 20 healthy individuals without anti-SARS-CoV-2 IgG constituted the control group. Key laboratory parameters, such as fibrinogen concentrations, soluble fibrin monomer complex (SFMCs), and Ddimer, were investigated. In addition, the qualitative composition of the fraction of SFMCs was analyzed. RESULTS: The slight increase in the concentration of fibrinogen, SFMCs, and D-dimers in some donor groups have been found, which could cause the development of hemostasis disorders. In the fraction of SFMCs, the increase in the number of protein fragments with a molecular weight of less than 250 kDa and an increase in the level of proteins with a molecular weight of more than 270 kDa was revealed. CONCLUSION: The obtained results indicated the relationship between the changes in the parameters of the hemostasis system and the titers of anti-SARS-CoV-2 IgG in donors in the post-COVID period. It can be assumed that donors with higher titers of anti-SARS-CoV-2 IgG (>55 ± 5 Index (S/C)) are more prone to hemostasis abnormalities in the post-COVID period since a pronounced imbalance in the levels of SFMCs and D-dimer characterizes them. The appearance of protein fragments of different molecular weights in the fraction of SFMC points to uncontrolled activation of biochemical processes involving molecules of fibrinogenic origin. Additional studies are required to elucidate the role of anti-SARS-CoV-2 IgG in the post-COVID period.