Hydroxychloroquine, azithromycin and methylprednisolone and in hospital survival in severe COVID-19 pneumonia.

Introduction: Severe COVID-19 pneumonia has two phases that are not mutually exclusive. Repurposed drugs target only one phase and the association of combination therapy to survival is unknown. Objective: To determine the association of hydroxychloroquine, azithromycin, and methylprednisolone versus methylprednisolone only to in hospital survival. Methods: This is a secondary analysis of a retrospective cohort of patients admitted for severe covid-19 in 13 hospitals in New Jersey, United States from March-June 2020. Propensity score match with 11 variables was constructed between those who received no methylprednisolone and methylprednisolone. Multivariate Cox regression was used for risk of in hospital mortality. Measurements and main results: There were 759 patients, 380 in no methylprednisolone and 379 with methylprednisolone. Multivariate Cox regression shows that methylprednisolone, hydroxychloroquine, and azithromycin had prolonged survival compared to methylprednisolone alone [HR 0.45 (95% CI 0.22,0.91 p < 0.03)]. In patients who received hydroxychloroquine and azithromycin, those who also received high dose methylprednisolone were associated with worse survival compared to those who received low dose methylprednisolone (HR = 1.642; 95% CI 1.053 to 2.562; p = 0.0287). Nursing home residents [HR 2.77 (95% CI 1.67, 4.59 p < 0.0001)], coronary artery disease [HR 2.93 (95% CI 1.31, 3.15 p = 0.001), and invasive mechanical ventilation [HR 3.02 (95% CI 1.71,5.34 p = 0.0001)] were independently associated with worse survival. Conclusion: Combination therapy was associated with improved survival compared to monotherapy. However, nursing home residents, coronary artery disease, and mechanical ventilation were independently associated with mortality. Larger randomized controlled studies are needed to confirm conclusions.

Racial/ethnic disparities on inflammation and response to methylprednisolone in severe COVID-19 pneumonia.

BACKGROUND: Racial/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 disparities with inflammatory markers and association of methylprednisolone to in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort study of patients ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 Hospitals in New Jersey, United States. Patients who received other formulation of corticosteroids were not included. Area under the receiver operating characteristics curves were performed to test for discriminatory ability of each inflammatory makers. Univariate and multivariate Cox regression assessed the association of variables to in hospital survival. RESULTS: Propensity 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. Compared to CRP, area under receiving operating characteristic curve for d-dimer in Hispanics (0.742) was statistically different (DeLong Test P = 0.0041). Multivariate cox regression showed that different variables in Blacks [age ≥ 60 years (HR = 3.71, P = 0.0281), mechanical ventilation (HR = 5.07, P = 0.0281) and creatinine ≥ 1.5 mg/dL (HR = 3.61, P = 0.0007)], Whites [cancer (HR = 1.68, P = 0.0213), qSOFA score of 1 (HR = 1.81, P = 0.0213), qSOFA score of 2 (HR = 5.16, P < 0.0001), qSOFA score of 3 (HR = 11.81, P < 0.0001) and creatinine ≥ 1.5 mg/dL (HR = 2.16, P = 0.0006)], Hispanics [hypertension (HR = 2.52, P = 0.0007), cancer (HR = 2.99, P = 0.0244 and D-dimer ≥ 2 mcg/mL (HR = 2.22, P = 0.0077)], and Asian/Indians [ chronic kidney disease (HR = 6.36, P = 0.0031) and CRP > 20 mg/L (HR = 5.02, P = 0.0032)] were statistically significant for mortality. Low dose and high dose methylprednisolone were significantly associated with prolonged survival in Whites [low dose (HR = 0.37, P < 0.0001) and high dose (HR = 0.48, P < 0.0183)] and Asian/Indians [low dose (HR = 0.13, P = 0.0101) and high dose (HR = 0.15, P = 0.01)]. However, high dose was not associated with improved survival compared to low dose. Methylprednisolone was not associated with prolonged survival in Blacks and Hispanics. CONCLUSION: Racial/Ethnic disparities with inflammatory markers preclude the use of one marker as a predictor of survival. Methylprednisolone is associated with prolonged survival in Asian/Indians and Whites.

Methylprednisolone and 60 Days in Hospital Survival in Coronavirus Disease 2019 Pneumonia.

OBJECTIVES: To determine methylprednisolone's dose, duration, and administration from onset of symptoms and association with 60 days in hospital survival of coronavirus disease 2019 pneumonia. DESIGN: Cohort study. SETTING: Thirteen hospitals in New Jersey, United States during March to June 2020. PATIENTS: Seven-hundred fifty-nine hospitalized coronavirus disease 2019 patients. INTERVENTIONS: We performed a propensity matched cohort study between patients who received methylprednisolone and no methylprednisolone. Patients in the methylprednisolone group were further differentiated into dose (high dose and low dose), duration, and administration from onset of symptoms. MEASUREMENTS AND MAIN RESULTS: In the propensity matched sample, 99 out of 380 (26%) in no methylprednisolone, 69 out of 215 (31.9%) in low-dose methylprednisolone, and 74 out of 164 (55.2%) high-dose methylprednisolone expired. Overall median survival for no methylprednisolone (25.0 d), low-dose methylprednisolone (39.0 d), high-dose methylprednisolone (20.0 d), less than or equal to 7 days duration (19.0 d), 7-14 days duration (30.0 d), greater than 14 days duration (44.0 d), onset of symptoms less than or equal to 7 days (20.0 d), and onset of symptoms 7-14 days (27.0 d) were statistically significant (log-rank p ≤ 0.001). Multivariate Cox regression showed nursing home residents, coronary artery disease, and invasive mechanical ventilation were independently associated with mortality. Methylprednisolone was associated with reduced mortality compared with no methylprednisolone (hazard ratio, 0.40; 95% CI, 0.27-0.59; p < 0.001) but no added benefit with high dose. Low-dose methylprednisolone for 7-14 days was associated with reduced mortality compared with less than or equal to 7 days (hazard ratio, 0.45; 95% CI, 0.22-0.91; p = 0.0273), and no additional benefit if greater than 14 days (hazard ratio, 1.27; 95% CI, 0.60-2.69; p = 0.5434). Combination therapy with tocilizumab was associated with reduced mortality over monotherapy (p < 0.0116). CONCLUSIONS: Low-dose methylprednisolone was associated with reduced mortality if given greater than 7 days from onset of symptoms, and no additional benefit greater than 14 days. High dose was associated with higher mortality.

Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection.

BACKGROUND: Characterizing the prevalence and persistence of symptoms associated with COVID-19 infection following hospitalization and their impact is essential to planning post-acute community-based clinical services. This study seeks to identify persistent COVID-19 symptoms in patients 35 days post-hospitalization and their impact on quality of life, health, physical, mental, and psychosocial function. METHODS AND FINDINGS: This prospective cohort study used the PROMIS® Instruments to identify symptoms and quality of life parameters in consecutively enrolled patients between March 22 and April 16, 2020, in New Jersey. The 183 patients (median age 57 years; 61.5% male, 54.1% white) reported persistent symptoms at 35 days, including fatigue (55.0%), dyspnea (45.3%), muscular pain (51%), associated with a lower odds rating general health (41.5%, OR 0.093 [95% CI: 0.026, 0.329], p = 0.0002), quality of life (39.8%; OR 0.116 [95% CI: 0.038, 0.364], p = 0.0002), physical health (38.7%, OR 0.055 [95% CI: 0.016, 0.193], p <0.0001), mental health (43.7%, OR 0.093 [95% CI: 0.021, 0.418], p = 0.0019) and social active role (38.7%, OR 0.095 [95% CI: 0.031, 0.291], p<0.0001), as very good/excellent, particularly adults aged 65 to 75 years (OR 8·666 [95% CI: 2·216, 33·884], p = 0·0019). CONCLUSIONS: COVID-19 symptoms commonly persist to 35 days, impacting quality of life, health, physical and mental function. Early post-acute evaluation of symptoms and their impact on function is necessary to plan community-based services.