Methylprednisolone was Associated with Reduced in-Hospital Mortality in COVID-19 Patients with Low Lymphocyte Counts: a Multicenter Retrospective Propensity Analysis

Background: To assess the effect of methylprednisolone on the prognosis of patients with novel coronavirus pneumonia.Methods: Patients with confirmed novel coronavirus pneumonia discharged from Wuhan Third Hospital Guanggu Campus, Shouyi Campus, and Lei Shen Shan Hospital from January 31, 2020, to March 4, 2020, were included. The patients were divided into treatment and control groups according to whether methylprednisolone was used during hospitalization. Propensity score (PS) matching analysis was used to assess in-hospital mortality as the primary outcome and trends in the changes in lymphocytes and the C-reactive protein, creatinine and transaminase levels 7 days after admission (secondary outcomes).Results: A total of 2,062 patients with confirmed novel coronavirus pneumonia were included in this study. Univariate Cox regression analysis suggested that methylprednisolone treatment was associated with increased in-hospital mortality (hazard ratio (HR) 3.70, 95% confidence interval (CI) 2.62-5.23, P<0.01). A total of 624 patients were included after PS matching. The patients were further subdivided into a low lymphocyte count group and a normal lymphocyte count group according to a lymphocyte count cutoff value of 0.9*109/L. Kaplan-Meier survival curve analysis showed that methylprednisolone treatment reduced the risk of in-hospital death in patients with lymphocyte counts less than 0.9×109/L (P=0.022). In contrast, in the normal lymphocyte group, methylprednisolone treatment was not associated with in-hospital mortality (p=0.88).Conclusion: Treatment with methylprednisolone may be associated with reduced in-hospital mortality in coronavirus disease (COVID) patients with low lymphocyte counts.

Methylprednisolone Treatment Versus Standard Supportive Care for Adult Covid19 Mechanically Ventilated, Acute Respiratory Distress Syndrome Patients

A myriad of symptoms presented by severely ill mechanically ventilated Covid19 patients has added pressure on the caregivers to explore therapeutic options. Systemic steroids have been reported to therapeutically benefit patients with elevated inflammatory markers, during the severe acute respiratory syndrome, and the Middle East respiratory syndrome outbreak. Covid19 disease is characterized by inflammation of the respiratory system and acute respiratory distress syndrome. Given the lack of specific treatment for Covid19, the aim of the current study was to evaluate the therapeutic benefit of methylprednisolone as an add-on treatment for mechanically ventilated hospitalized COVID19 patients with severe covid pneumonia. Data was collected retrospectively from the electronic patient medical records, and inter-rater reliability was determined to limit selection bias. Descriptive and inferential statistical methods were used to analyze the data. The variables were cross-tabulated with the clinical outcome and the Chi-Square test used to determine association between the outcomes and other independent variables. Patients. Sixty-one percent (43/70) of the Covid19 ARDS patients received standard supportive care, and the remainder were administered. methylprednisolone (40 mg daily to 40 mg q 6 hours). A 28-day all-cause mortality rate, in the methylprednisolone group was 18% (5/27, p < 0.01) significantly lower, compared to the group receiving standard supportive care (51%, 22/43). The median number of days, for the hospital length of stay (18 days), ICU-length of stay (9.5 days), and the number of days intubated (6 days) for the methylprednisolone treated group was significantly lower (p < 0.01), when compared with the standard supportive care group. Methylprednisolone treatment also reduced the C-reactive protein levels, compared to the standard care group on day 7. Our results strengthen the evidence for the role of steroids in reducing mortality, ICU LOS, and ventilator days in mechanically ventilated Covid 19 patients with respiratory distress syndrome.

Methylprednisolone Treatment in Brain Death-Induced Lung Inflammation–A Dose Comparative Study in Rats

Background: The process of brain death (BD) leads to a pro-inflammatory state of the donor lung, which deteriorates its quality. In an attempt to preserve lung quality, methylprednisolone is widely recommended in donor lung management. However, clinical treatment doses vary and the dose-effect relation of methylprednisolone on BD-induced lung inflammation remains unknown. The aim of this study was to investigate the effect of three different doses methylprednisolone on the BD-induced inflammatory response.Methods: BD was induced in rats by inflation of a Fogarty balloon catheter in the epidural space. After 60 min of BD, saline or methylprednisolone (low dose (5 mg/kg), intermediate dose (12.5 mg/kg) or high dose (22.5 mg/kg)) was administered intravenously. The lungs were procured and processed after 4 h of BD. Inflammatory gene expressions were analyzed by RT-qPCR and influx of neutrophils and macrophages were quantified with immunohistochemical staining.Results: Methylprednisolone treatment reduced neutrophil chemotaxis as demonstrated by lower IL-8-like CINC-1 and E-selectin levels, which was most evident in rats treated with intermediate and high doses methylprednisolone. Macrophage chemotaxis was attenuated in all methylprednisolone treated rats, as corroborated by lower MCP-1 levels compared to saline treated rats. Thereby, all doses methylprednisolone reduced TNF-α, IL-6 and IL-1β tissue levels. In addition, intermediate and high doses methylprednisolone induced a protective anti-inflammatory response, as reflected by upregulated IL-10 expression when compared to saline treated brain-dead rats.Conclusion: We showed that intermediate and high doses methylprednisolone share most potential to target BD-induced lung inflammation in rats. Considering possible side effects of high doses methylprednisolone, we conclude from this study that an intermediate dose of 12.5 mg/kg methylprednisolone is the optimal treatment dose for BD-induced lung inflammation in rats, which reduces the pro-inflammatory state and additionally promotes a protective, anti-inflammatory response.

Percentage of Myeloid Dendritic Cells in Peripheral Venous Blood Is Negatively Related to Incidence of Graves’ Orbitopathy

The aim of the study was to evaluate the distribution of blood dendritic cells (DCs) in patients with Graves’ orbitopathy (GO) and to assess the influence of methylprednisolone therapy on subsets of peripheral blood mononuclear cells (PBMCs). Peripheral blood DC subsets were analyzed by flow cytometry in patients with active GO ( n = 17 ), inactive GO ( n = 8 ), and Graves’ disease (GD) without GO ( n = 8 ) and controls ( n = 15 ); additionally, in patients with active GO ( n = 17 ), analyses were done at three time points, i.e., before methylprednisolone treatment and after 6 weeks and after 12 weeks of the treatment. Percentage of myeloid DCs (mDCs) in PBMC fraction was significantly lower in patients with both active and inactive GO, compared to patients with GD without GO and controls ( p < 0.05 ). In addition, mDCs were also documented to be an independent factor negatively associated with GO, however without essential differences between active and inactive phases. On the other hand, we did not observe any changes in the percentage of DCs after methylprednisolone therapy ( p > 0.05 ). In the present study, we have succeeded to firstly demonstrate—according to our knowledge—that blood mDCs are negatively related to GO incidence.

Clinical and Paraclinical Measures Associated with Outcome in Cerebral Amyloid Angiopathy with Related Inflammation

Background: Cerebral amyloid angiopathy with related inflammation (CAA-ri) is a rare age-associated disorder characterized by an inflammatory response to amyloid in cerebral blood vessels. CAA-ri is often treated with corticosteroids, but response to treatment is variable. Objective: To assess the relationship between clinical and paraclinical measures and outcomes in patients with CAA-ri treated with high doses of methylprednisolone. Methods: Longitudinal clinical course, and results from serum and cerebrospinal fluid (CSF) testing, electroencephalography, and neuroimaging were reviewed from 11 prospectively-accrued CAA-ri patients diagnosed, treated, and followed at Barnes Jewish Hospital (St. Louis, MO, USA). Magnetic resonance imaging (MRI) changes were quantified using a scoring system validated in cases of amyloid related imaging abnormality (ARIA-E). Clinical outcomes were assessed as change in modified Rankin Scale (ΔmRS) from baseline to final assessment (median 175 days from treatment with high doses of methylprednisolone; range, 31–513). Results: Worse outcomes following methylprednisolone treatment were associated with requirement for intensive care unit admission (median ΔmRS, 5 versus 1.5; p = 0.048), CSF pleocytosis (median ΔmRS 4.5 versus 1; p = 0.04), or lower CSF Aβ 40 at presentation (rho = –0.83; p = 0.02), and diffusion restriction (median ΔmRS 4 versus 1.5; p = 0.03) or higher late ARIA-E scores (rho = 0.70; p = 0.02) on MRI, but not preexisting cognitive decline (median ΔmRS 2 versus 2; p = 0.66). Conclusion: Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness.

The Effect of Immunosuppression on Selected Antioxidant Parameters in Patients with Graves’ Disease with Active Thyroid-Associated Orbitopathy

Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.

A retrospective study evaluating efficacy and safety of compassionate use of tocilizumab in 13 patients with severe-to-critically ill COVID-19: analysis of well-responding cases and rapidly-worsening cases after tocilizumab administration

We administered tocilizumab into 13 severe-to-critically ill patients with coronavirus disease 2019 (COVID-19) for compassionate use in combination with potential anti-viral agents in those who required an oxygen supply and showed increased laboratory inflammatory markers such as C-reactive protein (CRP) and ferritin. One injection of tocilizumab led to rapid improvements in clinical features, inflammatory findings, and oxygen supply in seven patients with severe COVID-19 and substantial amelioration in two patients who were critically ill, whereas four patients, who exhibited rapidly worsened respiratory function, required artificial ventilatory support even after tocilizumab treatment. Three of these four patients ultimately recovered from deterioration after methylprednisolone treatment. Administration of tocilizumab did not affect viral elimination nor IgG production specific for the virus. Compared with well-responding patients, rapidly-worsened patients showed a significantly higher ratio of ferritin vs. CRP. These findings suggest that tocilizumab has beneficial effects in severe-to-critically ill patients with COVID-19; however, in some cases, addition of methylprednisolone is required for disease rescue.