1 Forest storyline of pooled mortality of severely ill coronavirus disease 2019 (COVID-19) individuals from included studies Our meta-analysis had several limitations: (1) most?included studies were retrospective analysis of cases, resulting in poor quality of the included studies; (2) the uniformity of the diagnostic criteria for severe COVID-19 needs to be improved, and the extraction of related factors is limited; and (3) extraction of the original data is incomplete, and some data cannot be converted due to the lack of relevant data

1 Forest storyline of pooled mortality of severely ill coronavirus disease 2019 (COVID-19) individuals from included studies Our meta-analysis had several limitations: (1) most?included studies were retrospective analysis of cases, resulting in poor quality of the included studies; (2) the uniformity of the diagnostic criteria for severe COVID-19 needs to be improved, and the extraction of related factors is limited; and (3) extraction of the original data is incomplete, and some data cannot be converted due to the lack of relevant data. In summary, this is the 1st meta-analysis demonstrating the efficacy of tocilizumab treatment in severely ill COVID-19 patients. Acknowledgements Not applicable. Abbreviations ACEIAngiotension converting enzyme inhibitorsARBAngiotension receptors blockersARDSAcute respiratory stress syndromeCOVID-19Coronavirus disease 2019CIConfidence intervalsCRSCytokine launch syndromeFiO2Portion of inspired oxygenICUIntensive care unitIL-6Interleukin-6IMVInvasive mechanical ventilationNSAIDNon-steroidal anti-inflammatory drugsNIVNon- invasive VentilationOROdds ratioPaO2Partial pressure of oxygenSaO2Oxygen saturationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2 Authors contributions TBP Argireline Acetate contributed the conception and design of this review; ZJ published the paper. stress (ARDS), the latteris a leading cause of death for severe COVID-19 [3]. Uncontrolled immune activation would result Temocapril in cytokine storm, also known as cytokine release syndrome (CRS), appearing as overproduction of pro-inflammatory cytokines and chemokines [4]. Severe COVID-19 individuals constantly present elevated inflammatory markers, among which the elevation of IL-6 is definitely associated with severity of COVID-19 [5]. Besides, the upregulated manifestation of IL-6 receptor (IL-6R) was also recognized in COVID-19 individuals [6]. Consequently, IL-6/IL6R might serve as a messenger not only for transmitting inflammatory signals throughout the lung and additional organs but also by activating cellular signal pathway, therefore causing ARDS and multiple organ dysfunction. It is sensible to speculate that IL-6 blockade is beneficial for avoiding poor prognosis. Table 1 Study characteristics and demographics of included seriously ill coronavirus disease Temocapril 2019 (COVID-19) individuals thead th rowspan=”1″ colspan=”1″ Article /th th rowspan=”1″ colspan=”1″ Study design /th th rowspan=”1″ colspan=”1″ Country /th th rowspan=”1″ colspan=”1″ Total individuals /th th rowspan=”1″ colspan=”1″ Mean/median age (years) /th th rowspan=”1″ colspan=”1″ Standard care /th th rowspan=”1″ colspan=”1″ Tocilizumab treatment /th th rowspan=”1″ colspan=”1″ Individuals category /th th rowspan=”1″ colspan=”1″ Main results /th /thead Campochiaro C Eur J Intern Med 2020 Single-center retrospective cohort studyItaly6560 (control) 64 (tocilizumab) Hydroxychloroquine, lopinavir/ritonavir, ceftriaxone, azithromycinFirst intravenous 400?mg, second 400?mg was administered due to progressive respiratory worseningSevere COVID-19 individuals with hyper-inflammatory features admitted outside ICU requiring NIV and/or high-flow supplemental O2Security, efficacyCapra R Eur J Intern Med 2020 Retrospective observational studyItaly8570 (control) 63 (tocilizumab) Hydroxychloroquine, lopinavir/ritonavirTocilizumab once within 4?daysCOVID-19-related pneumonia and respiratory failure, not needing mechanical ventilationSurvival rateColaneri M Microorganisms 2020 Retrospective case-control studyItaly11264 (control) 62 (tocilizumab) Hydroxychloroquine, azithromycin, low weight heparin, methylprednisoloneFirst administration was 8?mg/kg (up to a maximum 800?mg per dose) intravenously, repeated after 12?hCritically ill patients with severe COVID-19 pneumoniaAdmission to the ICU and 7-day mortality rateGokhale Y EClinicalMedicine 2020 Retrospective cohort studyIndia16155 (control) 52 (tocilizumab) Antibiotics, hydroxychloroquine oseltamivir, low molecular weight heparin, methylprednisoloneA single intravenous dose of 400?mgCOVID-19 with oxygen saturation of 94% or less despite giving supplemental oxygen of 15?L/min via non-rebreathing face mask or PaO2/FiO2 percentage of less than 200DeathGuaraldi G Lancet Rheumatol 2020 Retrospective observational cohort studyItaly54469 (control) 64 (tocilizumab) Oxygen supply to target SaO2 reaching at least 90%, hydroxychloroquine, azithromycin in the physicians discretion when suspecting a bacterial respiratory super-infection, lopinavirCritonavir or darunavirCcobicistat, low molecular excess weight heparinIntravenous tocilizumab was administered at 8?mg/kg bodyweight (up to a maximum of 800?mg) administered twice, 12?h apart; the subcutaneous formulation was used when there was a shortage of the intravenous formulation, at a dose of 162?mg administered in two simultaneous doses, 1 in each thighSevere pneumonia defined at least one of the following: presence of a respiratory rate of 30 or more breaths per minute, peripheral blood SaO2 of less than 93% in space air, a percentage of PaO2 to FiO2 of less than 300?mmHg in space air flow, and lung infiltrates of more than 50% within 24C48?h, according to Chinese management recommendations for COVID-19Death or invasive mechanical ventilationKlopfenstein T Med Mal Infect 2020 Retrospective case-control studyFrance4571 (control) 77 (tocilizumab) Hydroxychloroquine or lopinavir-ritonavir, antibiotics, less commonly corticosteroids1 or 2 doses (no fine detail was reported)All critically COVID-19 individuals in tocilizumab group, fewer critically ill individuals in controlDeath and/or ICU admissionsMoreno-Prez O J Autoimmun 2020 Temocapril Retrospective cohort studySpain23657 (control) 62 (tocilizumab) No fine detail was reportedInitial 600?mg, with a second or third dose (400?mg) in case of persistent or progressive diseaseSevere COVID-19 pneumoniaAll-cause mortalityPotere N Ann Rheum Dis 2020 Retrospective caseCcontrol studyItaly8054 (control) 56 (tocilizumab) Hydroxychloroquine, darunavir/cobicistat, lopinavir/ritonavir, systemic corticosteroid324?mg given mainly because two concomitant subcutaneous injectionsSevere COVID-19 pneumonia with hypoxemia (oxygen saturation? ?90% on room air) requiring supplemental oxygen through nasal cannulas or maskRequirement of IMV or deathRojas-Marte GR QJM: An International Journal of Medicine 2020Retrospective, caseCcontrol, Temocapril single-center studyUSA19362 (control) 59 (tocilizumab) Hydroxychloroquine, azithromycin, corticosteroids anticoagulation, remdesivir, antibiotics for suspected bacterial infections, vasopressorsNo fine detail was reportedAdult individuals hospitalized with severe COVID-19Overall mortality rateSomers EC Clin Infect Dis 2020 Randomized controlled trialUSA15460 (control) 55 (tocilizumab) Hydroxychloroquine, remdesivir, NSAIDs, ACEI/ARB, vasopressors, anticoagulation corticosteroidThe standard tocilizumab dose was 8?mg/kg (maximum 800?mg) 1, additional doses were discouragedSevere COVID-19 individuals requiring mechanical ventilationSurvival probability after intubation Open in a separate window Open in a separate window Fig. 1 Forest storyline of pooled mortality of seriously ill.