Abstract
Background and objectives : COVID-19 patients exhibit a broad range of manifestations, presenting with a flu-like respiratory tract infection that can advance to a systemic and severe disease characterized by pneumonia, pulmonary edema, severe damage to the airways, and acute respiratory distress syndrome (ARDS, causing fatality in 70% of COVID-19 cases). A ‘cytokine storm’ profile is found in most severely influenced COVID-19 patients. The treatment protocol of the disease also includes tocilizumab, which is a humanized monoclonal antibody used to treat autoimmune and inflammatory conditions. This study was designed (1) to assess the role of tocilizumab in COVID-19 patients regarding therapeutic efficacy through evaluation of cytokine release syndrome (CRS) resolution and anticoagulant effect, analyzing clinical safety via monitoring of associated adverse effects profile; and (2) to compare the clinical safety and therapeutic efficacy of institutional treatment regimen (alone) versus tocilizumab added to an institutional treatment module in COVID-19 patients. Materials and Methods: In this study, the endpoints parametric assessment of severely diseased patients of COVID-19 was performed (total n = 172, control group (institutional protocol treatment provided), n = 101 and test group (tocilizumab provided), n = 71) at the Khyber Teaching Institution, MTI, Peshawar. The assessments were compared using non-parametric analyses at baseline and after a follow-up of 12-18 days until the patient discharged or expired. Results : Results of the study revealed an insignificant difference among the control vs. test group in resolving inflammatory parameters (C-reactive protein (CRP) 21.30 vs. 50.07; p = 0.470, ferritin 482.9 vs. 211.5; p = 0.612, lactate dehydrogenase (LDH) 29.12 vs.18.8; p = 0.0863, and D-dimer 464 vs.164.4; p = 0.131). However, a statistically significant difference was found between the control group and test group regarding coagulation parameters (international normalized ratio (INR) 0.12 vs. -0.07; p ≤ 0.001; activated partial thromboplastin time (aPTT) 0.42 vs. -1.16; p ≤ 0.001; prothrombin time (PT) 0.31 vs. -0.96; p ≤ 0.001; platelet count -12.34 vs. -1.47; p = 0.012) and clinical survival rate (89.10 vs. 90.14; p < 0.001). Furthermore, there was significantly higher infection rates and raised alanine aminotransferase (ALT) and alkaline phosphatase (ALP) associated with the tocilizumab group as compared to those receiving institutional treatment (bacterial infections: 0.99% vs. 15.49%; p ≤ 0.01, ALT: 3.96% vs. 28.16%; p ≤ 0.01, ALP: 1.98% vs. 22.53%; p ≤ 0.01). Conclusions : From this study, it was concluded that tocilizumab can be a better drug of choice in terms of efficacy, particularly in resolving coagulopathy in severe COVID-19 patients.
Keywords: COVID-19; coagulopathy; inflammatory parameters; tocilizumab.
【저자키워드】 COVID-19, Coagulopathy, tocilizumab., inflammatory parameters, 【초록키워드】 Treatment, Efficacy, ARDS, Cytokine storm, Tocilizumab, Pneumonia, respiratory tract infection, LDH, C-reactive protein, CRP, D-dimer, ferritin, lactate dehydrogenase, Cytokine release syndrome, International, Treatment protocol, Platelet, Manifestations, Pulmonary edema, Autoimmune, Follow-up, survival rate, infection rate, assessment, Teaching, COVID-19 patients, Bacterial, acute respiratory distress, fatality, CRS, Anticoagulant, ALT, Inflammatory, severe disease, COVID-19 cases, COVID-19 patient, airways, Prothrombin time, alanine aminotransferase, alkaline phosphatase, adverse effect, Endpoint, control group, institution, therapeutic efficacy, syndrome, severe COVID-19 patients, statistically significant difference, treatment regimen, treat, institutional protocol, material, inflammatory conditions, humanized monoclonal antibody, Result, include, the patient, the disease, raised, provided, receiving, was performed, characterized, activated, added, analysis, significantly higher, discharged, presenting, ALP, baseline, coagulation parameter, expired, inflammatory parameter, INR, normalized, patients of COVID-19, 【제목키워드】 Safety, clinical, assessment,