The coronavirus disease 2019 (COVID-19) pandemic began in Wuhan, China, on December 2019, caused by severe acute respiratory distress syndrome coronavirus (SARS-CoV-2), a new coronavirus related to bat-origin SARS-like viruses. It quickly spread globally due to its high transmissibility, leading to a wide range of disease severities, from asymptomatic to fatal, among certain populations, such as the elderly and those with pre-existing morbidities, being more vulnerable. Over time, SARS-CoV-2 developed multiple variants, including Alpha, Beta, Delta and Omicron, with Omicron showing the most mutations and highest spread. The disease course has been divided into three phases: the initial or first phase, characterized by virus invasion and replication, with clinical mild symptoms; the second phase, with immunity responses and predominant respiratory clinical symptoms; the third or last phase, usually in 10–20% of cases progressing to systemic inflammation or hyperinflammation phase, eventually resulting in intensive care unit treatment. The three phases have presented consistent overlap in many patients. However, the virus primarily affects the vascular system, causing “angiocentric inflammation” characterized by endothelial dysfunction, inflammation and intravascular clotting, which can lead to multiorgan failure. The virus enters cells through angiotensin-converting enzyme 2 (ACE2) receptors, triggering immune responses and inflammatory damage, and progresses through stages: viral replication, pulmonary inflammation and hyperinflammation, which can lead to acute respiratory distress syndrome (ARDS). COVID-19 also causes the cytokine storm, characterized by an overactive immune response that worsens tissue damage. Additionally, the virus affects platelets, neutrophils and the complement system, leading to intravascular clotting and further inflammation. COVID-19 is increasingly recognized as a systemic vascular disease, affecting microcirculation, and in some individuals, it leads to long-term effects known as long COVID. The fight against the virus requires ongoing monitoring of new variants and a deeper understanding of the disease’s pathophysiological processes across its various stages. The disease’s focus on the vascular system calls for further research into the interactions between endothelial cells and pericytes, both under normal conditions and during viral infection, to clarify their role in disease progression. Additionally, improving viscometric techniques to analyze the blood of COVID-19 patients could provide crucial insights into the effects on microcirculation. Advancing in vivo assessments of microcirculation through sublingual methods could also enhance understanding of the mechanisms behind microvascular damage in COVID-19 patients.