Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (–108.19; CI 95% –140.15, –75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

Tocilizumab treatment leads to early resolution of lymphopenia and myeloid dysregulation in patients hospitalized with COVID-19

“…IL-6 plays a critical role in driving the pro-inflammatory acute phase of antiviral responses, as well as in switching the inflammatory response from an acute, neutrophil-driven response to an inflammatory response characterized by recruitment of monocytes and differentiation of macrophages (9). The complex role of IL-6 has made it difficult to decipher the involvement of IL-6 in the pathology of Multiple studies have assessed the benefit of tocilizumab, an anti-IL-6 receptor (IL-6R) alpha antibody, in patients hospitalized with COVID-19 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and have individually shown mixed results, possibly due to heterogeneity of the patient population, timing of treatment, shifting standard of care (e.g., systemic corticosteroids), and insufficient sample size. In particular, COVACTA was a global, double-blind, randomized, placebo-controlled, phase 3 trial of 452 patients hospitalized with COVID-19 randomized to tocilizumab or placebo treatment (12).…”

Comparing the efficacy of tocilizumab with corticosteroid therapy in treating COVID-19 patients: a systematic review and meta-analysis

“…81% male, 25% hypertensive, 27% diabetic 4—5 Tocilizumab 8 mg/kg IV up to maximum of 800 mg IV N = 49 Hydroxychloroquine, azithromycin, beta-lactams, lopinavir-ritonavir N = 47 November 2020 Tsai et al [ 47 ] Single-centre, USA 132 Mean age 62.38 ± 13.49 in treatment group, 61.35 ± 16.09 in SOC group 73% male, 54.6% hypertensive, 30.3% diabetic 4—5 Tocilizumab 80.3% received 400 mg while 19.6% received > 400 mg. Four patients received second dose N = 66 Hydroxychloroquine, azithromycin, antibiotics (cephalosporins, piperacillin/tazobactam) N = 66 December 2020 Tian et al[ 48 ] Multi-centre, China 195 Median age 69.0 [62.0 – 75.0] 67% male,52.8% hypertensive, 16.9% diabetic 4—5 Tocilizumab 4 -8 mg/kg IV up to 800 mg IV N = 65 Antibiotic therapy, Antiviral therapy (lopinavir-ritonavir, ganciclovir, oseltamivir) N = 130 January 2021 Rajendram et al[ 49 ] Multi-centre, USA 444 Mean age 64 ± 12 in treatment group, 64 ± 13 in control group.33% diabetic, 4—5 Tocilizumab Doses not stated N = 102 Remdesivir, lopinavir-ritonavir, hydroxychloroquine, azithromycin N = 342 April 2021 Huang et al[ 50 ] Single centre, USA 96 Mean age 66.59 ± 19.10 in treatment group, 63.22 ± 16.29 in SOC group. 80% male, 60% hypertensive and 49% diabetic in treatment group 4—5 Tocilizumab A single 400 mg IV infusion N = 55 Hydroxychloroquine, remdesivir, azithromycin N = 41 June 2021 Sanchez-Rovira et al[ 52 , 51 ] …”

“…Of these 24 studies, seven studies that showed favourable outcomes involved tocilizumab [ 30 , 32 , 37 – 41 ]. The one study involving dexamethasone, Fusina et al [ 51 ] failed to reduce COVID-19 mortality (OR 1.28 95% CI 0.99 -1.67) while the two studies included that used methylprednisolone alone (Mikulska et al, OR 0.32, 95% CI 0.10 – 1.03; Nelson et al, OR 0.42 95% CI 0.16—1.15) did not show significant mortality reduction [ 43 , 44 ].

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“…Of these 24 studies, seven studies that showed favourable outcomes involved tocilizumab [30,32,[37][38][39][40][41]. The one study involving dexamethasone, Fusina et al [51] failed to reduce COVID-19 mortality (OR 1.28 95% CI 0.99 -1.67) while the two studies included that used methylprednisolone alone (Mikulska et [43,44]. Interestingly, two studies involving tocilizumab co-treated with methylprednisolone gave positive outcomes in reducing mortality [37,43].…”

The effect of low-molecular-weight heparin combined with amikacin on the coagulation function and bacterial clearance in the treatment of patients with severe senile pneumonia

“…The increase in fiber composition of lung tissue, and the occurrence of hypoxemia, hypoxemia and uncontrolled lung inflammation can lead to lung tissue injury, and in severe cases, to life threatening septic shock. 14 – 1 caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality.…”