Breaking down the clotting conundrum: analyzing the role of plasma tissue plasminogen activator in COVID-19 patients through a systematic review and meta-analysis

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INTRODUCTION: The SARS-CoV-2 virus pandemic has been a global challenge for medical services in terms of patient care and early prognosis of hospitalized patients' situations. Early identification and classification of COVID-19 patients in hospitals is critical for optimal management. The purpose of this study is to compile existing data on tissue plasminogen activator (tPA) concentrations in COVID-19 patients. MATERIAL AND METHODS: A systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Qualified articles were found systematically using relevant databases such as PubMed Central, Scopus, EMBASE, and the Cochrane databases until May 4 th , 2023. RESULTS: Tissue plasminogen activator levels among COVID-19 positive vs negative patients T-PA levels among COVID-19 positive vs negative patients varied and amounted to 26.67 ± 40.65 vs 4.68 ± 3.83, respectively (SMD = 2.49; 95% CI: 1.85 to 3.14; p < 0.001). The mean t-PA level among patients requiring ICU admission was 24.06 ± 12.44, compared to 16.55 ± 10.01 for patients not treated in the ICU (SMD = 0.69; 95% CI: −0.68 to 2.05; p = 0.32). Moreover, t-PA levels among severe COVID-19 compared to non-severe were 11.89 ± 9.05 and 16.87 ± 20.39, respectively (SMD = 2.74; 95% CI: −0.71 to 6.19; p = 0.12). The t-PA values were, respectively: 15.33 ± 8.01 for patients who survived hospital discharge, and 19.04 ± 11.88 for patients who died in hospital due to COVID-19 (SMD = −0.50; 95% CI: −2.45 to 1.44; p = 0.61). CONCLUSIONS: According to this meta-analysis, the key conclusion of this study is that COVID-19 infection is connected to t-PA levels. Nonetheless, extensive prospective studies addressing the possible diagnostic relevance of t-PA as a marker of COVID-19 severity are required to corroborate the presented results.