COVID-19 Disease, Women’s Predominant Non-Heparin Vaccine-Induced Thrombotic Thrombocytopenia and Kounis Syndrome: A Passepartout Cytokine Storm Interplay

Abstract

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions.

The Involvement of CXC Motif Chemokine Ligand 10 (CXCL10) and Its Related Chemokines in the Pathogenesis of Coronary Artery Disease and in the COVID-19 Vaccination: A Narrative Review

“…The development of selective evasins or evasin-like peptides that may be differentially expressed that bind and even neutralize CXCL9/CXCL10 versus CXCL11 could offer an interesting therapeutic alternative to limit the pathogenic and preserve the regulatory CXCR3 functions. The early cytokine/chemokine signature featuring IL-15, IFN-g and CXCL10 may be involved in the pathogenesis of myocardial damage, myocardities and thromboses [110,121] but may also be involved to monitor effective vaccinations and as a guide to optimize the efficacy of the mRNA vaccination [111].…”

“…The severity of COVID-19 disease is related to an uncontrolled inflammation and the ensuing cytokine storm. Indeed, an increase in multiple type 2 effectors IL-5, IL-8, eosinophils, immunoglobulin E, type 2 antibody isotype IgE and CXCL10 were found in severe form of the disease and continued to increase during the course of disease [109,110]. However, an early but transient inflammatory cytokine response with increased CXCL10, IFN-g, IP-10/, IL-6 and CRP was observed at day 2 and returned to baseline levels by day 8 following a COVID-19 vaccination with BNT162b2 mRNA (Pfizer/BioNtech).…”

Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases

“…The PF4/polyanion pair act as autoantigen-inducing antibodies of the IgG class. On the other hand, PF4-polyanion-IgG complexes can also be detected in 3-5% of healthy subjects, with a risk of platelet aggregation via FcRIIa/CD32 receptors on their surface, which could be a common pathway for VITT, HIT, or DIC syndromes [4,5,7,8,16,57,58]. Similarly, spike proteins during COVID-19 infection have also been demonstrated to cause PF4 degranulation, platelet aggregation, and thrombosis [4,64,65].…”

“…However, side effects have been reported after vaccine shots. Rare serious Vaccines 2022, 10, 232 2 of 15 adverse events such as vascular syndromes, myocarditis, pericarditis, neurological disease, and other illnesses have been described in a variable proportion of recipients [1][2][3][4][5]. Vascular thrombosis occurred in some individuals, particularly young women, at times surprisingly involving the cerebral venous sinus (CVS) vessels.…”

Acute Myocardial Infarction Within 24 Hours After COVID-19 Vaccination: Is Kounis Syndrome the Culprit?

“… 11 Alternatives to these excipients, such as alkylsaccharides, are promising agents because they can reduce immunogenicity, improve stability, suppress oxidative damage problems, and may prevent thrombotic and cardiovascular events. 12 COVID-19 free allergenic vaccines would be beneficial.…”