Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia

Background Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. Methods This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. Results In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). Conclusion Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Use of tocilizumab, remdesivir, and high-dose methylprednisolone prevents intubation in an ESRD patient with COVID-19 pneumonia

Coronavirus disease 2019 (COVID-19) has affected over 200 million patients worldwide. COVID-19 is transmitted through respiratory droplets from patient to patient or by touching a surface that has been contaminated by an infected patient. Many COVID-19 patients have other comorbidities, such as end-stage renal disease. Currently, management of COVID-19 in patients with end-stage renal disease is unclear. Some studies have shown improvement in this population with the use of tocilizumab, a humanized interleukin-6 monoclonal antibody, in addition to the standard therapy as per guidelines published by the National Institutes of Health. In this case report, we present a patient case where the use of remdesivir, tocilizumab, and pulse-dose methylprednisolone significantly improved symptoms and inflammatory biomarkers associated with COVID-19 in a patient with end-stage renal disease.

Low versus High Dose Methylprednisolone in Adult Patients with COVID-19: Less is More

Background Corticosteroids use in severe COVID-19 improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). Methods This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on 17 November 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (1 September to 15 November 2020) were compared to the LDC group (30 November 2020 to 20 January 2021). HDC was defined as methylprednisolone 80 mg daily in two divided doses and LDC was defined as methylprednisolone 32-40 mg daily in two divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. Results Four-hundred and seventy patients were included; 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, p=0.712). This finding remained intact when controlling for additional variables (OR 0.947, [CI 0.515-1.742], p=0.861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (p&lt;0.001). No differences were noted in any of the other secondary outcomes. Conclusions Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Macrophage activation syndrome in MDA5 antibody-positive dermatomyositis and COVID-19 infection

Background Macrophage activation syndrome (MAS) is a rare multiorgan system disorder that may present as a fatal complication of underlying rheumatological disease, including dermatomyositis. Case presentation Here, we report the case of a 65-year-old Caucasian female with a history of psoriasis and a recent diagnosis of Coronavirus disease 2019 (COVID-19) who presented with progressive generalized weakness, joint pains, an erythematous rash, shortness of breath, and weight loss. She was ultimately diagnosed with biopsy-confirmed melanoma differentiation-associated protein 5 (MDA5)-positive dermatomyositis complicated by MAS, requiring intravenous immunoglobulin and high-dose methylprednisolone. Conclusions This report serves as a clinical reminder of the rare, yet clinically relevant association between MDA5-positive dermatomyositis and MAS, as well as highlights the potential contribution of other immune system activating diseases, such as COVID-19, associated with a cytokine storm and hyperinflammatory state.

Racial/ethnic Disparities on Inflammation and Response to Methylprednisolone in Severe Covid-19 Pneumonia

BACKGROUNDRacial/Ethnic minorities are at higher risk for Severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic differences between the inflammatory markers of survivors and non-survivors and if there was a dose dependent association of methylprednisolone to in hospital survival. METHODSThis was a secondary analysis of a retrospective cohort. Patients were older than 18 years of age and admitted for severe COVID-19 Pneumonia Between March to June 2020 in 13 Hospitals in New Jersey, United States. Comparison of inflammatory markers used Kruskal-Wallis followed by pairwise comparison using two-sided Wilcoxon rank sum test. A Youden Index Method was used to determine the cut-off between low dose and high dose methylprednisolone. For each racial/ethnic group, cox regression was used to determine the association to survival between no methylprednisolone and methylprednisolone (high dose versus low dose). RESULTSPropensity matched sample (n=759) between no methylprednisolone (n=380) and methylprednisolone (n=379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 Non-Black Non-White Hispanics. Interleukin-6, C-reactive protein, ferritin, and d-dimer values were higher in non-survivors compared to survivors except in Asian/Indian survivors who had higher ferritin values compared to non-survivors (median: 1,265 vs 418 ug/L, P=0.0211). Black and Hispanic survivors had persistently elevated C-reactive protein, (10.2 mg/mL) and (13.70 mg/mL) respectively. Low dose methylprednisolone was associated with prolonged 60 days in hospital survival over no methylprednisolone in Whites (P<0.0001), Asian/Indians (P=0.0180), and Hispanics (P=0.0004). Regardless of dose, methylprednisolone was not associated with prolonged survival in Blacks. High dose methylprednisolone was associated with worse survival in Hispanics. (P=0.0181). CONCLUSIONRacial/Ethnic disparities with inflammatory markers in survivors and non-survivors preclude the use of one marker as predictor of survival. Low dose methylprednisolone is associated with prolonged survival in Asian/Indians, Hispanics, and Whites. Methylprednisolone, regardless of dose, was not associated with prolonged survival in Blacks.

High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis

Corticosteroids are largely recommended in patients with severe COVID-19. However, evidence to support high-dose methylprednisolone (MP) pulses is not as robust as that demonstrated for low-dose dexamethasone (DXM) in the RECOVERY trial. This is a retrospective cohort study on severe, non-critically ill patients with COVID-19, comparing 3-day MP pulses ≥ 100 mg/day vs. DXM 6 mg/day for 10 days. The primary outcome was in-hospital mortality, and the secondary outcomes were need of intensive care unit (ICU) admission or invasive mechanical ventilation (IMV). Propensity-score matching (PSM) analysis was applied. From March 2020 to April 2021, a total of 2,284 patients were admitted to our hospital due to severe, non-critically ill COVID-19, and of these, 189 (8.3%) were treated with MP, and 493 (21.6%) with DXM. The results showed that patients receiving MP showed higher in-hospital mortality (31.2% vs. 17.8%, p < 0.001), need of ICU admission (29.1% vs. 20.5%, p = 0.017), need of IMV (25.9% vs. 13.8, p < 0.001), and median hospital length of stay (14 days vs. 11 days, p < 0.001). Our results suggest that treatment with low-dose DXM for 10 days is superior to 3 days of high-dose MP pulses in preventing in-hospital mortality and need for ICU admission or IMV in severe, non-critically ill patients with COVID-19.

HTLV-1 encephalitis

A 53-year-old woman developed subacute onset of upper limb weakness, sensory loss and cerebellar dysfunction. She was known to have human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy. MR scan of the brain showed extensive T2 hyperintensity within the deep and subcortical white matter, with punctate contrast enhancement. Cerebrospinal fluid (CSF) was lymphocytic with very high levels of HTLV-1 provirus in both CSF and peripheral blood lymphocytes. We diagnosed HTLV-1 encephalomyelitis and started high-dose methylprednisolone followed by a slow corticosteroid taper. She recovered well and regained functional independence in the upper limbs. Neurological manifestations of HTLV-1 infection extend beyond classical ‘tropical spastic paraparesis’ and are under-recognised. We review the literature on HTLV-1 encephalitis and discuss its diagnosis and management.