Tocilizumab for severe COVID-19: a systematic review and meta-analysis

Lan, Shao Huan; Lai, Chih Cheng; Huang, Hui; Chang, Shen Peng; Lü, Li; Hsueh, Po-Ren

doi:10.1016/j.ijantimicag.2020.106103

Cited by 143 publications

(137 citation statements)

References 24 publications

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“…In these patients, glucocorticoids at high doses and/or IVs TCZ have become the treatment of choice in real life [20]. Although some retrospective and observational studies using TCZ in severe COVID-19 have shown promising results [9][10][11][12][13], other studies, including the preliminary results of randomized trials, and a systemic review and meta-analysis did not demonstrate a benefit for TCZ in improving clinical status or reducing the risk of ICU admission and mortality [21,22]. However, TCZ may be effective in particular subgroups of patients, as we showed in this study in patients underlying NIV or Somers et al in patients requiring invasive mechanical ventilation [23].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation

et al. 2020

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Background The severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extremely variable, ranging from asymptomatic patients to those who develop severe acute respiratory distress syndrome (ARDS). As for now, there are still no really effective therapies for coronavirus disease 2019 (COVID-19). Some evidences suggest that tocilizumab (TCZ) may avoid the progression of severe COVID-19. The aim of this retrospective case-control study was to analyze the efficacy and safety of TCZ in patients with COVID-19 ARDS undergoing noninvasive mechanical ventilation (NIV). Methods Seventy-nine consecutive patients with severe COVID-19 pneumonia and worsening acute respiratory failure (ARF) were admitted to the Pulmonology Unit of Azienda USL of Reggio Emilia-IRCCS. All patients were inflamed (elevated CRP and IL-6 levels) and received NIV at admission according to the presence of a pO2/FiO2 ratio ≤ 200 mmHg. The possibility of being treated with TCZ depended on the drug availability. The primary outcome was the in-hospital mortality rate. A secondary composite outcome of worsening was represented by the patients who died in the pulmonology unit or were intubated. Results Out of 79 patients, 41 were treated with TCZ. Twenty-eight patients received intravenous (IV) TCZ and 13 patients received subcutaneous (SC) TCZ. In-hospital overall mortality rate was 38% (30/79 patients). The probabilities of dying and being intubated during the follow-up using Kaplan-Meier method were significantly lower in total patients treated with TCZ compared to those of patients not treated with TCZ (log-rank p value = 0.006 and 0.036, respectively). However, using Cox multivariate analyses adjusted for age and Charlson comorbidity index only the association with the reduced risk of being intubated or dying maintained the significance (HR 0.44, 95%CI 0.22–0.89, p = 0.022). Two patients treated with TCZ developed cavitating lung lesions during the follow-up. Conclusions This study shows that TCZ treatment may be effective in COVID-19 patients with severe respiratory impairment receiving NIV. More data on safety are required. Randomized controlled trials are needed to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation

et al. 2020

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“…Because the lack of RCTs [12], both SRMA only included observational studies, in which TCZ was given at a single dose of 400-800 mg iv or 162-324 mg sc, renewable once in case of insufficient response to therapy. The first SRMA, published by Lan SH Zhang et al [13], included 7 studies, with no conclusive evidence that TCZ would provide any additional benefit to patients with severe COVID-19. The second, registered in the medRxiv repository by Boregowda et al [14] included 16 studies, concluding that the addition of TCZ to the SOC might reduce the mortality in severe COVID-19.…”

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confidence: 99%

Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

Rubio‐Rivas¹,

Ronda²,

Padullés³

et al. 2020

Preprint

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Introduction: On the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ, with or without CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ, with or without CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (SD 4.3) and 4.3 days (SD 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in combined therapy with TCZ, was the main protective factor against in-hospital mortality.

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“…Efficacy of immunosuppressive treatments for severe COVID-19 is still debated. In particular for tocilizumab, a recent meta-analysis did not show any additional benefit for patients with severe COVID-19 [19]. The authors concluded that further recommendations on tocilizumab should wait results from on-going clinical trials, due to the low quality of evidence of the available studies.…”

Section: Discussionmentioning

confidence: 97%

“…The recent emergence of SARS-CoV-2 and its rapid spread throughout all continents has become a global concern [1]. Many studies have recently been conducted to identify the molecular pathway leading to alveolar damage in moderate and severe Coronavirus disease 2019 (COVID- 19), and have shown the pivotal role of the hyperinflammatory response of the patients' immune system to the virus in determining alveolar destruction [2]. This is the rationale for the use of corticosteroids, to counteract respiratory failure in severely ill patients, along with oxygen supply [3].…”

Section: Introductionmentioning

confidence: 99%

Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia

et al. 2020

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Background SARS-CoV-2 pandemic has posed formidable public health and clinical challenges. The use of immunosuppressive agents, such as high dose corticosteroids and cytokine inhibitors (e.g., Tocilizumab) has been suggested to contrast the hyperinflammatory process involved in the pathogenesis of the severe disease, with conflicting evidence. Among the drawbacks of immunosuppressive therapy, the risk of reactivation of latent infections, including parasitic infestations, is to be considered. Case presentation We report a case of a 59-year-old Italian patient treated with high dose intravenous dexamethasone and two intravenous doses of Tocilizumab for interstitial bilateral pneumonia associated with SARS-CoV-2 infection who developed itching, abdominal pain, and an increased eosinophil count. Stool examination confirmed the presence of S. stercoralis larvae. The patient was treated with a 4-day course of Ivermectin with full recovery. Discussion We report the first case of S. stercoralis infection following an 11-day treatment with high-dose steroids and Tocilizumab for severe COVID-19. Clinicians should be aware of the risk of strongyloidiasis as a complication of the treatment for severe COVID-19.

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Tocilizumab for severe COVID-19: a systematic review and meta-analysis

Cited by 143 publications

References 24 publications

Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation

Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation

Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia

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