Efficacy of tocilizumab in patients with severe COVID-19: Survival and clinical outcomes

Albaadani, Abeer; Eltayeb, Nazik; Alsufyani, Eid; AlBahrani, Salma; Basheri, Shareefah; Albayat, Hawra; Batubara, Enas; Ballool, Sulafa; Assiri, Ayed Al; Faqihi, Fahad; Musa, Ali B.; Robert, Asirvatham Alwin; Alsherbeeni, Nisreen; Elzein, Fatehi

doi:10.1016/j.jiph.2021.05.015

Cited by 9 publications

(9 citation statements)

References 31 publications

(36 reference statements)

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“…Among studies that assessed the mortality of COVID-19 patients on tocilizumab in Saudi Arabia, our study reported an overall mortality of 21%. In comparison, other studies reported 16.1% (n = 62) 28-day mortality [36]. In terms of mortality among ICU patients, the current study reported 38.5%, while other studies reported 31.1% (n = 61) [37] and 18.9% (n = 37) [38] mortality.…”

Section: Discussioncontrasting

confidence: 88%

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Safety of Tocilizumab in COVID-19 Patients and Benefit of Single-Dose: The Largest Retrospective Observational Study

et al. 2022

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Severe acute respiratory coronavirus-2 (SARS-CoV-2) still presents a public threat and puts extra strain on healthcare facilities. Without an effective antiviral drug, all available treatment options are considered supportive. Tocilizumab as a treatment option has to date shown variable results. In this retrospective study, we aimed to assess predictors of mortality of COVID-19 patients (n = 300) on tocilizumab and the clinical effectiveness of this drug. The results showed that ICU admission OR = 64.6 (95% CI: 8.2, 507.4); age of the patient OR = 1.1 (95% CI: 1.0, 1.1); and number of tocilizumab doses administered by the patient OR(two doses) = 4.0 (95% CI: 1.5, 10.9), OR(three doses) = 1.5 (95% CI: 0.5, 5.1), and OR(four doses or more) = 7.2 (95% CI: 2.0, 25.5) presented strong correlation factors that may be linked to COVID-19 mortality. Furthermore, our study showed the beneficial effects of early administration of tocilizumab OR = 1.2 (95% CI: 1.1, 1.4) and longer hospital length of stay OR = 0.974 (95% CI: 0.9, 1.0) in reducing COVID-19 mortalities. High blood D-dimer concentration OR = 1.1 (95% CI: 1.0, 1.2) and reciprocal blood phosphate concentration OR = 0.008 (95% CI: 0.0, 1.2) were correlated to high mortality under SARS-CoV-2 infection. The short-term effect of a single dose of tocilizumab was a significant increase in blood BUN and liver enzymes (ALT, AST, and LDH) above their normal ranges. Furthermore, it significantly reduced CRP blood concentration, but not to normal levels (13.90 to 1.40 mg/dL, p < 0.001). Assessing the effect of different doses of tocilizumab (in terms of the number of doses, total mg, and total mg/kg administered by the patients) indicated that administering more than one dose may lead to increases in ICU length of stay and hospital length of stay of up to 14 and 22 days after the last dose of tocilizumab (6 to 14, p = 0.06, and 10 to 22, p < 0.001), with no improvement in 28- and 90-day mortality, as confirmed by Kaplan–Meier analysis. There were also clear correlations and trends between the number of doses of tocilizumab and increased blood CO2, MCV, RDW, and D-dimer concentrations and between number of doses of tocilizumab and decreased CRP, AST, and hemoglobin concentrations. Microbiology analysis showed a significant increase in the incidence of infection after tocilizumab administration (28 to 119, p < 0.001) with a median time of incidence within 6 days of the first dose of tocilizumab. A significant correlation was also found between the number of tocilizumab doses and the number of incidences of infections after tocilizumab administration r (298) = 0.396, p = 1.028 × 10−12. Based on these results and depending on the pharmacokinetic parameters of the drug, we recommend single-dose administration of tocilizumab as the optimal dosage for COVID-19 patients who do not have active bacterial infection or liver diseases, to be administered as soon as the patient is admitted to the hospital.

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Section: Discussioncontrasting

confidence: 88%

“…Hypercytokinemia and its associated hyperinflammatory and immunodeficiency are reported to be responsible for lethal complications and increased mortality in COVID-19 patients [ 6 , 33 , 34 , 35 , 36 ]. Accordingly, the findings of this study provide valuable detail to guide the use of tocilizumab in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Safety of Tocilizumab in COVID-19 Patients and Benefit of Single-Dose: The Largest Retrospective Observational Study

et al. 2022

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“…In a recent research article, a trial that examined survival varied with baseline CRP levels demonstrated the administration of Tocilizumab was beneficial in patients with CRP levels greater than 15.0 g/L [ 21 ]. Some studies have also evaluated the Tocilizumab treatment in patients with severe COVID-19, suggesting its efficacy on mortality [ 22 , 23 , 24 ]. The TCZ efficacy on mortality on day 14 and 28 was retrospectively evaluated in 62 patients (57.4 ± 14.3 years) who received one to two doses of TCZ (400–800 mg every 12 h) [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have also evaluated the Tocilizumab treatment in patients with severe COVID-19, suggesting its efficacy on mortality [ 22 , 23 , 24 ]. The TCZ efficacy on mortality on day 14 and 28 was retrospectively evaluated in 62 patients (57.4 ± 14.3 years) who received one to two doses of TCZ (400–800 mg every 12 h) [ 22 ]. There was a significant difference in the 28-day (TCZ = 62 and control = 86) and in the 14-day (9.7% vs. 24.4%, p = 0.022) fatality rate among the TCZ-treated patients and control group.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Single Tocilizumab Administration in an 88-Year-Old Patient with Severe COVID-19 and a Mini Literature Review

et al. 2022

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The new coronavirus disease 2019 (COVID-19) could be associated with elevated inflammatory cytokine levels, suggesting the involvement of cytokine release syndrome. This syndrome is characterized by release of interleukin 6 correlated with COVID-19 severity and mortality. Targeting IL-6 with Tocilizumab treatment could be a potential therapeutic option for old patients. We report the case of an 88-year-old man with COVID-19 disease who presented at the admission with anemia, fever, oxygen desaturation (92%), and inflammatory syndrome (C-reactive protein (CRP) at 182.5 mg/L; reference range <5.0 mg/L). After remaining CRP level increase (206.6 mg/L), Tocilizumab administration led to rapid clinical outcome and resolution of his inflammatory syndrome. This case report represents a supplementary data confirming the efficacy and safety of Tocilizumab for COVID-19 in elderly patients.

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“…In COVID-19 related cytokine storm syndrome (COVID-CSS), different inflammatory cytokines such as Interleukin-1 (IL-1), Interleukin-10 (IL-10), and tumor necrosis factor (TNF)-α are elevated about 2-100 fold above normative values. In some patients with COVID-19, IL-6 levels rise more than 1,000 fold above normal range (Blanco-Melo et al, 2020;Herold et al, 2020;Laing et al, 2020;Al-Baadani et al, 2021). IL-6 signals through both classic and trans-signaling pathways, activates JAK-STAT3 signaling.…”

Section: Does Immune Dysregulation Predisposes Individual To Cancer Il-6/jak/stat Signaling Pathwaymentioning

confidence: 99%

Cancer Occurrence as the Upcoming Complications of COVID-19

Rahimmanesh

Shariati

Dana

et al. 2022

Front. Mol. Biosci.

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Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID‐19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi‐organ failure are hallmarks of severe COVID‐19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low‐grade inflammation in “long COVID‐19” syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.

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Efficacy of tocilizumab in patients with severe COVID-19: Survival and clinical outcomes

Cited by 9 publications

References 31 publications

Safety of Tocilizumab in COVID-19 Patients and Benefit of Single-Dose: The Largest Retrospective Observational Study

Safety of Tocilizumab in COVID-19 Patients and Benefit of Single-Dose: The Largest Retrospective Observational Study

Efficacy of Single Tocilizumab Administration in an 88-Year-Old Patient with Severe COVID-19 and a Mini Literature Review

Cancer Occurrence as the Upcoming Complications of COVID-19

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