Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context.

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.

COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines.

On January 30, 2020, the WHO declared the novel coronavirus of 2019 a pandemic, causing millions of cases and thousands of deaths worldwide, exposing the vulnerabilities of healthcare systems around the world with each country having its own experience. These ranged from patient clinical profiles to management recommendations and to government interventions. There is a paucity of published data regarding Philippine experience. This study is a retrospective, descriptive study of ninety-one COVID-19 probable patients admitted in the COVID ICU of The Medical City from March 16 to May 7, 2020. We described clinical and demographic characteristics amongst COVID-19-confirmed and -negative patients. Therapeutic interventions including COVID-19 investigational drug use and other organ failure strategies were noted and tested for association with ICU survivors and nonsurvivors. We observed that there was no therapeutic intervention that was associated with improved outcomes, with some interventions showing trends favoring the ICU nonsurvivor group. These interventions include, but are not limited to, the use of hydroxychloroquine and tocilizumab, and prone positioning. We also observed that a higher SAPS-3 score was associated with the COVID-19 positive group and the ICU nonsurvivor group. On PubMed search, there seems to be no Philippine-specific literature regarding COVID-19 ICU experience. Further investigations to include more variables are recommended.

Can Serum Fibrinogen Predict ARDS?

Acute respiratory distress syndrome (ARDS) has a worldwide mortality of 10% to 30% with severe pneumonia being the primary cause. Diagnosis relies on clinical criteria which may lead to under-recognition and delayed evidence-based interventions. In previous studies, plasma fibrinogen was associated with progression to ARDS among patients with severe pneumonia. This is a prospective cohort study wherein we hypothesized that levels of plasma fibrinogen and change in levels of fibrinogen can predict development of ARDS among a cohort of patients with severe pneumonia based on the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) consensus criteria. After acquiring consent, plasma fibrinogen levels were extracted upon enrollment and after 48 hours. These extraction times were arbitrarily chosen to determine whether levels rise or decline in relation to the course of disease. A total of 47 patients were prospectively followed within 7 days of enrollment, then divided into 2 groups, which included those who developed ARDS (n = 12, 25%) and those who did not (n = 35, 75%). Fibrinogen levels at baseline had sensitivity and specificity of 41.7% and 57.1%, respectively (P = .932) with an area under the curve (AUC) of 0.492; levels after 48 hours had sensitivity and specificity of 55.6% and 65.6%, respectively (P = .729) with an AUC of 0.538; and delta fibrinogen levels had sensitivity and specificity of 55.6% and 62.5%, respectively (P = 0.581) with an AUC of 0.561. Based on this study, plasma fibrinogen is an unreliable biomarker for predicting ARDS development in patients with severe pneumonia. In setting up this study, we experienced limitations which we had to accept but realizations of these led to the discovery of potential research areas. To our knowledge, this is the first Philippine study attempting to discover a biomarker for ARDS progression. It is recommended that further investigation on local incidence and other biomarkers for ARDS should be done.

The Fire from Within: Multiorgan Failure with Bimodal Rhabdomyolysis from Exertional Heat Stroke.

Heat stroke (HS) is a condition characterized by a rise in core body temperature and central nervous system dysfunction. It is divided into two types: classical and exertional. Exertional heat stroke (EHS) is accompanied by organ failure. Liver injury, presenting only with a rise in liver enzymes, is common but in rare conditions, acute liver failure (ALF) may ensue, leading to a potentially lethal condition. Most cases of EHS-induced ALF are managed conservatively. However, liver transplantation is considered for cases refractory to supportive treatment. Identifying patients eligible for liver transplantation in the context of an EHS-induced ALF becomes a medical dilemma since the conventional prognostic criterion may be difficult to apply, and there is paucity of literature about these specific sets of individuals. Recently, extracorporeal liver support has been gaining popularity for patients with liver failure as a bridge to liver transplant. In this case report, we present a young Filipino athlete with symptoms and clinical course consistent with EHS that developed multiorgan failure, initially considered a candidate for liver transplant and total plasma exchange, but clinically improved with supportive management alone. This patient was also found to have bimodal rhabdomyolysis during the course of his hospital stay as manifested by the bimodal rise in his creatine kinase enzymes.