ABSTRACT
To explore and summarize the association between treatment with tocilizumab and clinical outcomes in COVID-19 patients. We performed a systematic review and meta-analysis (10 RCTs including 3378 patients in the tocilizumab group and 3142 patients in the control group). We systematically searched PubMed and MedRxiv for all RCTs as of June 1, 2021, to assess the benefits and harms of tocilizumab to treat patients with COVID-19. All analyses were carried out using RevMan version 5.4.1. There were nine RCTs published in peer-reviewed journals and one RCTs published as a preprint. The summary RR for all-cause mortality with tocilizumab was 0.89 (95% CI= 0.82-0.96, P= 0.003). There was no significant between-trial heterogeneity (I2= 28%, P= 0.19). However, all peer-reviewed RCTs showed no significant associations between treatment with tocilizumab and reductions in all-cause mortality. We notably found that tocilizumab significantly reduced the rate of intubation or death in patients with COVID-19 with 3 RCTs. Across the 8 RCTs, the summary RR for discharge with tocilizumab was 1.10 (95% CI= 1.03-1.16, P< 0.00001). There was no significant association of tocilizumab with harm on other patient-relevant clinical outcomes, including increasing secondary infection risk, patients of adverse events, or patients of serious adverse events. Tocilizumab significantly increased the rate of hospital discharges in COVID-19 patients. Still, it did not decrease all-cause mortality or increase the risk of secondary infections, patients of adverse events, or patients for serious adverse events. Evidence that tocilizumab affects clinical outcomes in patients with COVID-19 requires further proof.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/mortality , Disease Progression , Humans , Patient Discharge/statistics & numerical data , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment OutcomeABSTRACT
As the pandemic progresses, the pathophysiology of coronavirus disease 2019 (COVID-19) is becoming clearer and the potential for immunotherapy is increasing. However, clinical efficacy and safety of immunosuppressants (including tocilizumab, sarilumab and anakinra) treatment in COVID-19 patients are not yet known. We searched PubMed, Embase Medline, Web of Science and MedRxiv using specific search terms in studies published from 1 January 2020 to 20 December 2020. In total, 33 studies, including 3073 cases and 6502 controls, were selected for meta-analysis. We found that immunosuppressant therapy significantly decreased mortality in COVID-19 patients on overall analysis (odds ratio = 0.71, 95% confidence interval = 0.57-0.89, p = 0.004). We also found that tocilizumab and anakinra significantly decreased mortality in patients without any increased risk of secondary infection. In addition, we found similar results in several subgroups. However, we found that tocilizumab therapy significantly increased the risk of fungal co-infections in COVID-19 patients. This represents the only systematic review and meta-analysis to investigate the efficacy and secondary infection risk of immunosuppressant treatment in COVID-19 patients. Overall, immunosuppressants significantly decreased mortality but had no effect on increased risk of secondary infections. Our analysis of tocilizumab therapy showed a significantly increased risk of fungal co-infections in these patients.
Subject(s)
COVID-19 Drug Treatment , Coinfection , Antibodies, Monoclonal, Humanized , Humans , Immunosuppressive Agents/adverse effects , Interleukin 1 Receptor Antagonist Protein/adverse effects , SARS-CoV-2ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. Based on a retrospective analysis of SARS and influenza data from China and worldwide, we surmise that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Although there are few publications, COVID-19 patients, especially severely ill or immunocompromised, have a higher probability of suffering from invasive mycoses. Aspergillus and Candida infections in COVID-19 patients will require early detection by a comprehensive diagnostic intervention (histopathology, direct microscopic examination, culture, (1,3)-ß-D-glucan, galactomannan, and PCR-based assays) to ensure effective treatments. We suggest it is prudent to assess the risk factors, the types of invasive mycosis, the strengths and limitations of diagnostic methods, clinical settings, and the need for standard or individualized treatment in COVID-19 patients. We provide a clinical flow diagram to assist the clinicians and laboratory experts in the management of aspergillosis, candidiasis, mucormycosis, or cryptococcosis as co-morbidities in COVID-19 patients.