SARS-CoV-2 infection triggers a series of complex pathophysiological events involving three main mechanisms: viral entry, cytokine storm, and multisystem injury. The process begins with binding of the viral spike protein to the ACE2 receptor. This interaction is facilitated by the TMPRSS2 protease, which promotes cleavage of the S protein and viral internalization. Genetic polymorphisms in these receptors modulate susceptibility and severity of infection. A literature search was conducted in PubMed, ScienceDirect, and LILACS databases between April and June 2025 using DeCS descriptors and associated MeSH terminology, ensuring a systematic and comprehensive approach. Filters were applied to include full-text, open-access articles published within the last five years. The search yielded 90 articles, of which 48 were selected based on title screening. Abstract reading subsequently led to the exclusion of 38 articles that did not meet established criteria, such as correlating more than one pathology, addressing pathological mechanisms in animal models, or describing therapeutic strategies for SARS-CoV-2. Ten articles were included in the present review. Following viral replication, dysregulated immune system activation is observed, characterized by excessive release of pro-inflammatory cytokines. This exacerbated response is directly associated with the development of diffuse tissue injury, coagulopathy, and acute respiratory distress syndrome. Massive recruitment of neutrophils and monocytes significantly contributes to pulmonary injury and respiratory failure. Concurrently, systemic endothelial dysfunction occurs, marked by increased vascular permeability, activation of the coagulation cascade, and microthrombus formation. Reduced ACE2 availability due to viral internalization disrupts the renin–angiotensin–aldosterone system, leading to angiotensin II accumulation. These mechanisms explain the high incidence of thromboembolic complications in severe cases. Viral dissemination compromises multiple organs, causing myocarditis and cardiac arrhythmias, as well as acute kidney injury through combined mechanisms of hypoxia and systemic inflammation. These complications result from both direct viral invasion and secondary immune responses. The pathophysiology of C-19 represents a balance between viral factors, host immune response, and systemic consequences, whose understanding is essential for clinical management.
Marchelli et al. (2026) studied this question.