The purpose of the present study is to see if the presence of angiotensin-converting enzyme 2 (ACE-2), transmembrane serine protease 2 (TMPRSS), and P-selectin in platelets increases the risk of thrombosis in COVID-19 patients. This was a cross-sectional study conducted in the COVID-19 isolation center between January and September 2021 and comprised 61 COVID-19-infected patients, 21 of whom were in the intensive care unit (ICU) and 40 of whom were non-ICU patients (non-ICUP) in the isolation center. The coagulation profile, as well as the ACE-2, TMPRES, and P-selectin receptors, were all assessed in addition to the complete blood count (CBC). A questionnaire was also utilized to collect social and demographic data. All platelet indices and coagulation profiles were significantly altered in COVID-19 ICUP and non-ICUP in this research; additionally, there is a significant association between the presence of ACE-2, P-selectin, and TMPRRS2 in COVID-19 patients with coagulation profile and platelet indices leading to hypercoagulable state. In summary, the interaction of ACE-2, TMPRSS, and P-selectin in platelets appears to be a key element contributing to COVID-19 severity via their impact on thrombus development. Further investigation into these pathways may provide possible treatment targets for reducing the severe consequences of the COVID-19 infection.