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BackgroundPending for randomized control trials, the use of tocilizumab (TCZ) in COVID-19 is based on observational studies and remains controversial. PurposeTo summarize evidence about the effect of TCZ to treat severe COVID-19. Data sourcesPubMed (via MEDLINE), Scopus, and medRxiv repository databases from 1 January to 21 August 2020. Study SelectionObservational studies in any language reporting efficacy and safety outcomes of TCZ use in hospitalized adults with COVID-19. Data ExtractionIndependent, dually performed data extraction and quality assessments. Data synthesisOf 57 eligible studies, 27 were controlled and 30 were not. The overall included patients were 8,128: 4,021 treated with TCZ, in addition to standard of care (SOC), and 4,107 only receiving SOC. The pooled mortality was lower in the TCZ-group vs. the control group, with a relative risk (RR) of 0.73 (95%CI 0.57-0.93; p = 0.010). The overall NNT to avoid one death was 20. In hospital wards, patients in the TCZ-group were transferred to intensive care unit (ICU) in a higher proportion than those in the control group; however, ICU mortality of the TCZ-group was lower than in the control group. Secondary infections occurred in a higher proportion in TCZ-treated patients. Among survivors, the length of stay was similar in both groups. LimitationsConclusions should be considered as weak evidence since they are based on observational studies, most of them retrospective. A variety of factors influencing the indication and effect of TCZ could not be evaluated in-depth. ConclusionsTCZ seems beneficial in preventing in-hospital mortality in severe, non-critically ill COVID-19 patients. Conversely, patients receiving TCZ appear to be at higher risk for secondary infections, especially those admitted to ICU. Funding sourceNo funding or sponsorship was received for this study or publication of this article. The protocol was published in the National Institute for Health Research international register of systematic reviews (PROSPERO); registration number CRD42020204934.
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IntroductionOn 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. MethodsFrom 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 +/-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. ResultsA 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 +/-CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 ({+/-} 4.3) and 4.3 days ({+/-} 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. ConclusionsIn severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed beneficial effect in preventing in-hospital mortality.