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IntroductionSome COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. Methods and analysisTACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature [≤] 37.5{degrees}C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate [≤]24 rpm; for 48 consecutive hours. DiscussionMethylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries. Trial registration numberNCT04341038 / EudraCT: 2020-001445-39
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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.