ABSTRACT
The pleiotropic cytokine interleukin-6 (IL-6) has been implicated in the pathogenesis of COVID-19, but uncertainty remains about the potential benefits and harms of targeting IL-6 signalling in patients with the disease. The efficacy and safety of tocilizumab and sarilumab, which block the binding of IL-6 to its receptor, have been tested in adults with COVID-19-related acute respiratory illness in randomised trials, with important differences in trial design, characteristics of included patients, use of co-interventions, and outcome measurement scales. In this Series paper, we review the clinical and methodological heterogeneity of studies of IL-6 receptor antagonists, and consider how this heterogeneity might have influenced reported treatment effects. Timing from clinical presentation to treatment, severity of illness, and concomitant use of corticosteroids are among the factors that might have contributed to apparently inconsistent results. With an understanding of the sources of variability in these trials, available evidence could be applied to guide clinical decision making and to inform the enrichment of future studies.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , COVID-19 , Clinical Trials as Topic , Receptors, Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/immunology , COVID-19/immunology , COVID-19/therapy , Clinical Trials as Topic/methods , Clinical Trials as Topic/statistics & numerical data , Humans , Patient Selection , Receptors, Interleukin-6/immunology , SARS-CoV-2Subject(s)
Burnout, Professional/psychology , Coronavirus Infections/psychology , Coronavirus Infections/therapy , Empathy , Family/psychology , Health Personnel/psychology , Health Personnel/statistics & numerical data , Pneumonia, Viral/psychology , Pneumonia, Viral/therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2ABSTRACT
Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic. It is known that SARS-CoV-2 infects the host through the cell surface receptor of angiotensin-converting enzyme 2 (ACE2), which is expressed in multiple organs, and in the arterial and venous endothelial cells. We have recently proposed the use of the term MicroCLOTS ( Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) to describe the unique type of ARDS seen in patients affected by SARS-COV-2. After a multidisciplinary assessment of more than 850 COVID-19 patients admitted to our Hospital with several bilateral pneumonia, we have collected evidences supporting a key role of vascular inflammation and microthrombosis in the pathophysiology of the multisystemic clinical manifestations that have been associated with COVID-19. There is now a general consensus on the recommendation of anticoagulation in patient with severe SARS-Cov2 infections, although the dose of the prophylaxis and even the choice between a prophylactic and a treatment regimen remains controversial. Randomized controlled trials are urgently needed to help clarifying the many therapeutic challenges associated with the management of SARS-Cov-2 patients.