Predictors of Mortality Amongst Tocilizumab Administered COVID-19 Asian Indians: A Premonition Study From a Tertiary Care Centre

Abstract

Introduction Hyper-cytokinemia is a dreaded complication of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and an important predictor of mortality in coronavirus disease 2019 (COVID-19). The current evidence at best is still ambiguous for use of tocilizumab in cytokine storm in COVID-19. Moreover, the factors that are associated with beneficial response from tocilizumab are unknown in COVID-19. We aimed to study the clinical outcomes especially mortality vis-à-vis clinical and laboratory characteristics of patients administered tocilizumab and identify predictors of mortality benefits amongst deceased vs recovered COVID-19 patients. Methods The present study is a retrospective observation of the demographic, clinical, and biological data of all the consecutive patients treated with tocilizumab for COVID-19 pneumonia at the COVID tertiary care centre from July 2020 to October 2020 at Ahmedabad, India. We compared the deceased group with those who recovered/discharged and evaluated patient-level demographics, clinical attributes, and laboratory investigations available to identify subgroups in whom tocilizumab reduced mortality. Results Of the 112 patients included, the mean (SD) age was 56.84 ± 13.56 years and 80 (71.4%) were male. There were 97 (86.6%) patients in the survivors and 15 (13.39%) in the deceased group. Deceased were older than the recovered group (mean: 66.14, SD: 14.41 vs mean: 55.36, SD: 12.98; p=0.04). Hypertension (33.03%) was the commonest comorbidity observed. Mortality was significantly higher in patients with cancer and type-2 diabetes (p=0.05 and p=0.01, respectively). Level of D-dimer and lactate dehydrogenase (LDH) showed trends towards significance as a predictor of mortality (p=0.07 and p=0.08, respectively) not reaching significance. D-dimer level > 5,000 nanograms per millilitre (ng/mL) was the significant predictor of subsequent deaths (p<0.0001). Fourteen patients reported adverse events of tocilizumab. Patients who developed in-hospital complications (such as septic or vasodilatory shock and/or sepsis, acute kidney injury, multiorgan dysfunction) had significantly higher mortality (p<0.0001, p=0.009, and p=0.03, respectively). Conclusion Tocilizumab might be more beneficial in younger patients without sepsis/ septic shock, acute kidney injury, multiorgan dysfunction, and who were non-ventilated. The predictors of mortality amongst Asian Indians treated with tocilizumab were older patients, the presence of type-2 diabetes, cancer, in-hospital complication (such as acute kidney injury, sepsis/septic shock, multiorgan dysfunction), higher D-dimer > 5,000 ng/mL. A larger study with pre-defined inclusion cutoffs of these variables may aid in defining patient's characteristics of Asian Indians who may benefit from tocilizumab in COVID-19.

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

“…There were more men than women in our cohort, and the percentage skewed even more in the deceased group, a common observation in COVID-19. However, in agreement with previous TCZ-cohorts of COVID-19, sex was not associated with the risk of death ( Moreno-Pérez et al, 2020 ; Morrison et al, 2020 ; Desai et al, 2021 ). On the contrary, risk death did increase with age, while literature shows contradictory results ( Moreno-Pérez et al, 2020 ; Morrison et al, 2020 ; Desai et al, 2021 ).…”

“…In our study, the comorbidities associated with a higher hazard of death were immunosuppression and diabetes mellitus. Diabetes mellitus has been largely associated to poorer outcomes in COVID-19 patients [reviewed in ( Huang et al, 2020b )], while contradictory results have been observed in cohorts under TCZ treatment ( Moreno-Pérez et al, 2020 ; Morrison et al, 2020 ; Desai et al, 2021 ). Obesity has been related to a higher risk of death in COVID-19 patients ( Demeulemeester et al, 2021 ) and may act as a cofounder or modifier variable for this finding.…”

“…In TCZ-COVID-19 cohorts, the effect of immunosuppression was not estimated ( Moreno-Pérez et al, 2020 ; Morrison et al, 2020 ) or the variable was included in the group of comorbidities, precluding a specific analysis ( Lohse et al, 2020 ; Galván-Román et al, 2021 ). Nevertheless, a publication recently reported a higher risk of death among cancer patients receiving TCZ due to COVID-19, but not among patients with previous rheumatology/infectious diseases ( Desai et al, 2021 ). Due to our study design, we cannot conclude whether the TCZ-induced immunosuppression acted as an added risk factor for death in previously immunocompromised patients.…”

Symptomatic Reinfection in Previously Recovered Coronavirus Disease 2019 (COVID-19) Geriatric Patient

“…and is associated with immunodeficiency as well as hyper inflammation, the latter manifesting as a cytokine storm [7]. COVID-19 was earlier thought to be a respiratory disease, but it has affected multiple organs [8][9][10][11].…”

Favipiravir-Induced Drug Fever in a Young Adult COVID-19 Patient

“…Coronavirus disease 2019 (COVID-19) has induced a negative effect on social, economic, and psychological well-being in addition to causing physical discomfort [ 2 ]. Hypercytokinemia, which usually appears in the second week of COVID-19 and is associated with immunodeficiency as well as hyperinflammation, also known as a cytokine storm, is a feature of SARS-CoV-2 [ 3 ]. COVID-19 was previously believed to be a pulmonary illness, but studies have shown that it also affects other tissues in the body [ 4 - 6 ].…”