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The Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) created a global pandemic that continues to this day. In addition to pulmonary symptoms, the virus can have destructive effects on other organs, especially the heart. For example, large pericardial effusion has been observed as a critical and life-threatening finding in Coronavirus disease of 2019 (COVID-19) patients. In this case report based systematic review, we review the reports of moderate to severe pericardial effusion associated with tamponade physiology. Direct cardiomyocyte and pericardium invasion, inflammation and cytokine storms and oxidative stress due to acute respiratory distress syndrome, are the pathogenesis of this phenomenon. The results showed that the manifestations of this finding are variable. Pericardial effusion can be seen as a delayed complication, accompanied by myocarditis or pericarditis, isolated, or with acute …