Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.

Late onset infectious complications and safety of tocilizumab in the management of COVID-19.

BACKGROUND: Tocilizumab (TCZ) has been used in the management of COVID-19-related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug-related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID-19 patients. METHODS: All adult inpatients with COVID-19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late-onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post-TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion-related reactions. RESULTS: Seventy-four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03). CONCLUSION: Late onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ-related toxicities, 61% of patients had a possible post-TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID-19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.

Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.

BACKGROUND: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing. STUDY DESCRIPTION: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease. CONCLUSIONS: This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.