Disertasi

Hubungan Parameter Perlekatan Virus, Surfaktan, Kerusakan Vaskular dan Inflamasi dengan Derajat Penyakit COVID-19: Kajian terhadap Kadar Furin, TMPRSS2, ACE2, PS-D, VEcadherin, XCL1/lymphotactin dan IL-6 = The Role of Virus Attachment, Surfactant, Vascular Damage, and Inflammation Biomarkers towards COVID-19 Severity: A Study on Furin, TMPRSS, ACE2, PS-D, VE-cadherin, XCL1/ lymphotactin and IL-6 Levels.

Patofisiologi COVID-19 belum diketahui sepenuhnya, sementara patofisiologi penting digunakan sebagai landasan pemahaman prediktor keparahan, gejala, dan tatalaksana COVID-19. Dalam penelitian ini, diteliti hubungan dan peran konsentrasi furin, TMPRSS2, ACE2, PS-D, VE-cadherin, XCL1/lymphotactin, dan IL-6 dalam sirkulasi darah terhadap derajat keparahan COVID-19. Studi ini merupakan studi case cohort. Sebanyak 120 pasien infeksi SARS-CoV-2 berusia > 18 tahun yang dirawat di RSUPN Cipto Mangunkusomo dan RS Medistra pada bulan Juni 2020 hingga Februari 2021 diikutsertakan dalam penelitian ini. Pasien dinilai berdasarkan karakteristik klinis yaitu usia, jenis kelamin, onset, komorbiditas, pemeriksaan darah lengkap, nilai cycle threshold (CT), penggunaan antiinflamasi, jenis antivirus, oksigenasi, dan mortalitas. Mortalitas diamati dalam 28 hari setelah perawatan. Kadar biomarker serum pasien diukur dengan metode ELISA untuk kelompok gejala tidak berat, berat, dan kritis. Kadar furin pada kelompok kritis lebih tinggi dibandingkan kelompok berat dan tidak berat dan kadar ACE2 dalam darah pada kelompok berat dan kritis lebih tinggi dibandingkan kelompok tidak berat dan berat sebagai dampak peningkatan ekspresi parameter perlekatan virus pada COVID-19. Kadar TMPRSS2 dan IL-6 darah kelompok berat menurun pada fase inflamasi diduga karena efek penggunaan steroid. Kadar PS-D darah kelompok berat dan kritis meningkat selaras dengan manifestasi kerusakan alveolus. Kadar XCL1 /lymphotactin kelompok kritis lebih rendah diduga dipengaruhi kondisi limfopenia yang disebabkan oleh migrasi limfosit menuju alveolus. Kadar VE-cadherin tidak berbeda bermakna pada setiap fase dan kelompok mengindikasikan patogenesis COVID-19 tidak melibatkan kerusakan sistem vaskular tingkat endotel. Pada kelompok meninggal ditemukan peningkatan kadar furin, ACE2, dan PS-D pada fase virus.
Kata kunci: Biomarker, COVID-19, derajat keparahan, inflamasi, mortalitas, patofisiologi, virus


Pathophysiology is essential for understanding predictors of severity, symptoms, and management of COVID-19; however, its complete understanding has yet to be achieved. The objective of this research endeavour was to examine the correlation and significance of blood circulation concentrations of furin, TMPRSS2, ACE2, PS-D, VE-cadherin, XCL1/lymphotactin, and IL-6 with respect to COVID-19 severity. We performed a case cohort study at Cipto Mangunkusumo and Medistra hospital, Jakarta. A total 120 patients with SARS-Cov-2 infection who were >18 years old who were admitted to the hospital from June 2020 through February 2021 were included in this study. Clinical characteristics (age, gender, onset, comorbidities, complete blood count, cycle threshold (CT) value, antiinflammatory, antiviral, oxygenation, and mortality) were utilized to evaluate patients. After admittance, mortality was observed within 28 days. The ELISA method was employed to quantify the serum biomarker concentrations of patients categorized as having non-severe, severe, or critical symptoms. Blood levels of furin was higher in the critical group compared to non-severe and severe group, while ACE2 levels were higher in both severe and critical groups compared to nonsevere and severe groups due to the higher expression of virus attachment parameters in COVID-19. The observed reduction in blood levels of TMPRSS2 and IL-6 in the severe group during the inflammation phase was hypothesized to be attributable to administration of steroids. In severe and critical groups, there was an increase in blood PS-D levels, which corresponded to the presence of alveolar damage. The reduced concentrations of XCL1 /lymphotactin observed in the critical group may be attributed to lymphopenia, a condition characterized by lymphocyte migration towards the alveoli. VE-cadherin levels did not differ markedly between phases and groups, suggesting that endothelial damage to the vascular system is not involved in the pathogenesis of COVID-19. Elevated concentrations of furin, ACE2, and PS-D during the viral phase were detected in the non-survivor group.
Keywords: Biomarker, COVID-19, inflammation, mortality, pathophysiology, severity