ABSTRACT
OBJECTIVES: Sepsis is one of the leading causes of morbidity and mortality within the healthcare system and remains a diagnostic and therapeutic challenge. A major issue in the diagnosis of sepsis is understanding the pathophysiologic mechanism, which revolves around host immune system activation and dysregulated responses. African Americans are more likely to experience severe sepsis with higher mortality rates compared to the general population. This pilot study characterized multiple inflammatory markers and proteases in plasma of primarily African American and Afro-Caribbean patients with mild sepsis. METHODS: Plasma was collected from 16 healthy controls and 15 subjects presenting with sepsis, on admission, and again upon resolution of the signs of sepsis, defined as a resolution of sepsis criteria. Plasma samples were analyzed for cytokines, chemokines, and proteases using multiplex bead assays. RESULTS: Elevated levels of granulocyte colony-stimulating factor, interleukin-10, interleukin-15, interleukin-1 receptor antagonist, interleukin-8, interferon gamma-induced protein 10, monocyte chemoattractant protein-1, matrix metallopeptidase 12, and cathepsin S were identified in plasma from sepsis patients on admission compared to control subjects. Interleukin-6, interleukin-8, granulocyte colony-stimulating factor, and cathepsin S were reduced in sepsis patients upon clinical resolution of sepsis. CONCLUSION: These findings profile the circulating inflammatory cytokines, chemokines, and proteases in African Americans and Afro-Caribbean patients during sepsis. The role of these targets in sepsis needs addressing in this patient population.
ABSTRACT
OBJECTIVES: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.
