Background: Coronavirus Disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with its cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications constitutes one of the deadliest pandemics in modern history. A common pathogenetic mechanism of these complications seems to be the Covid-19-induced excessive immune response of uncontrolled release of interleukins, chemokines, interferons, tumor necrosis factors and colony-stimulating factors, the so called cytokine storm syndrome. Severe anaphylactic reactions with profound hypotension or hypoxemia can be also associated with release of pro-inflammatory cytokines. Aim: Careful investigation for similarities in clinical manifestations and correlated multi-organ complications of Covid-19 with other viral infections including dengue and human immunodeficiency viruses together with the action of inflammatory cells inducing the Kounis syndrome could provide a better understanding on pathophysiolgy and trigger mechanisms, elucidating potential preventing and therapeutic strategies. Methods: A search was performed in Medline (via PubMed), for current literature on the pathophysiology, causality, clinical appearance, variance, prevention, and treatment of Covid-19, anaphylaxis with profuse hypotension and the Kounis anaphylaxis associated acute coronary syndrome. Results: Insights from research in allergy/anaphylaxis-associated cardiac syndromes and Covid-19, suggest that the same key immune cells are invollved in cardiovascular complications of Covid-19 and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with Covid-19 has been attributed to coronary spasm, plaque rupture and microthrombi, hypoxic injury or cytokine storm and shares the same patho-physiology with the 3 clinical variants of Kounis syndrome. Conclusion: The patho-physiology, etiology, clinical manifestations and therapeutic approaches of the severe Covid-19 and their associations might be proved beneficial for future treatments. Early immunological interventions targeting inflammatory markers that are predictive of worse disease outcome would be more beneficial than those blocking late-appearing cytokine related storm. Individualized, tailored to each patient treatment approach is required in Covid-19 cases