Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic.

BACKGROUND: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. METHODS: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. RESULTS: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates). CONCLUSION: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.

The Role of Hospital and Community Pharmacists in the Management of COVID-19: Towards an Expanded Definition of the Roles, Responsibilities, and Duties of the Pharmacist.

Since late December 2019, a novel, emerging coronavirus was identified as the infectious agent responsible for a generally mild but sometimes severe and even life-threatening disease, termed as "coronavirus disease 2019" (COVID-19). The pathogen was initially named as "2019 novel coronavirus" (2019-nCoV) and later renamed as "Severe Acute Respiratory Coronavirus type 2" (SARS-CoV-2). COVID-19 quickly spread from the first epicenter, the city of Wuhan, province of Hubei, mainland China, into neighboring countries, and became a global pandemic. As of July 15th 2020, the outbreak is still ongoing, with SARS-CoV-2 affecting 213 countries and territories. The coronavirus has caused a dramatic toll of deaths and imposed a severe burden, both from a societal and economic point of view. COVID-19 has challenged health systems, straining and overwhelming healthcare facilities and settings, including hospital and community pharmacies. On the other hand, COVID-19 has propelled several changes. During the last decades, pharmacy has shifted from being products-based and patient-facing to being services-based and patient-centered. Pharmacies have transitioned from being compounding centers devoted to the manipulation of materia medica to pharmaceutical centers, clinical pharmacies and fully integrated "medical-pharmaceutical networks", providing a significant range of non-prescribing services. Moreover, roles, duties and responsibilities of pharmacists have paralleled such historical changes and have known a gradual expansion, incorporating new skills and reflecting new societal demands and challenges. The COVID-19 outbreak has unearthed new opportunities for pharmacists: community and hospital pharmacists have, indeed, played a key role during the COVID-19 pandemic, suggesting that a fully integrated, inter-sectoral and inter-professional collaboration is necessary to face crises and public health emergencies. Preliminary, emerging evidence seems to suggest that, probably, a new era in the history of pharmacies ("the post-COVID-19 post-pharmaceutical care era") has begun, with community pharmacists acquiring more professional standing, being authentic heroes and frontline health workers.