Covid-19 disease, women’s predominant non-heparin vaccine-induced thrombotic thrombocytopenia and kounis syndrome: A passepartout cytokine storm interplay

Nicholas G. Kounis, Ioanna Koniari, Cesare De Gregorio, Stelios F. Assimakopoulos, Dimitrios Velissaris, Ming Yow Hung, Virginia Mplani, Luca Saba, Aikaterini Brinia, Sophia N. Kouni, Christos Gogos, Mattia Giovannini, Elio Novembre, Vinu Arumugham, Darrell O. Ricke, George D. Soufras, Kenneth Nugent, Piero Sestili, Robert W. Malone

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Article number959
Issue number8
Publication statusPublished - Aug 2021


  • Anaphylaxis
  • COVID-19
  • Cytokine storm
  • Heparin
  • Kounis syndrome
  • Thrombocytopenia
  • Thrombosis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology


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