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Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

ABSTRACT: Background:In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. Methods:We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results:Findings are reported as MP (n?=?83) vs control (n?=?90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P?=?.07) and 14 vs 26 (P?=?.10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0?±?9.0 vs 17.5?±?12.8; P?=?.001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P?=?.84). Conclusion:In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration.?ClinicalTrials.gov NCT04323592.

SUBMITTER: Salton F

PROVIDER: S-EPMC7543560 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

Salton Francesco F Confalonieri Paola P Meduri G Umberto GU Santus Pierachille P Harari Sergio S Scala Raffaele R Lanini Simone S Vertui Valentina V Oggionni Tiberio T Caminati Antonella A Patruno Vincenzo V Tamburrini Mario M Scartabellati Alessandro A Parati Mara M Villani Massimiliano M Radovanovic Dejan D Tomassetti Sara S Ravaglia Claudia C Poletti Venerino V Vianello Andrea A Gaccione Anna Talia AT Guidelli Luca L Raccanelli Rita R Lucernoni Paolo P Lacedonia Donato D Foschino Barbaro Maria Pia MP Centanni Stefano S Mondoni Michele M Davì Matteo M Fantin Alberto A Cao Xueyuan X Torelli Lucio L Zucchetto Antonella A Montico Marcella M Casarin Annalisa A Romagnoli Micaela M Gasparini Stefano S Bonifazi Martina M D'Agaro Pierlanfranco P Marcello Alessandro A Licastro Danilo D Ruaro Barbara B Volpe Maria Concetta MC Umberger Reba R Confalonieri Marco M

Open forum infectious diseases 20200912 10

<h4>Background</h4>In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.<h4>Method ...[more]

PMID: 33072814

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Project description:BackgroundThere is no effective therapy for the severe acute respiratory syndrome by coronavirus 2 (SARS-CoV2) responsible for the Coronavirus disease 2019 (Covid-19). To date, dexamethasone has shown a decrease in mortality in patients who require oxygen, especially those with invasive mechanical ventilation. However, it is unknown if another corticosteroid can be used, the optimal dose and its duration, to achieve a better clinical outcome. The objective of the study was to compare the differences in clinical outcome and laboratory results in hospitalized patients with severe SARS-CoV2 Pneumonia treated with dexamethasone at 6 mg doses versus patients treated with high-dose methylprednisolone.Materials and methodsAmbispective cohort study with survival analysis of 216 patients diagnosed with severe Covid-19 pneumonia confirmed by polymerase chain reaction for SARS-CoV2 by Berlin protocol, who were hospitalized in a high-complexity clinic in Medellín, Colombia. The patients should also have supplementary oxygen and radiological confirmation of Pneumonia by chest tomography. Sample size was not calculated since the total population that met the inclusion criteria was evaluated. 111 patients were treated with the institutional protocol with intravenous dexamethasone 6 mg QD for seven to 10 days if they required oxygen. Since September 15, 2020, the hospitalization protocol of the clinic was modified by the Infectious Diseases and Pulmonology service, recommending a high dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral prednisone 50 mg every day for 14 days. The protocol was not applied in the intensive care unit, where dexamethasone continued to be administered. The clinical outcome and differences in laboratory results of the patients who received dexamethasone vs. the prospective cohort that received methylprednisolone from September 15 to October 31, 2020, were evaluated. Follow-up was carried out by outpatient consultation one month after discharge or by telephone, inquiring about readmission or living-dead status.Results216 patients had Covid-19 pneumonia documented by ground-glass imaging and alveolar pressure / inspired oxygen fraction (PaFi) less than 300. 111 patients received dexamethasone (DXM) and 105 received methylprednisolone (MTP). Patients in the DXM group evolved to severe ARDS in a higher proportion (26.1% vs 17.1% than the MTP group). Upon completion 4 days of treatment with parenteral corticosteroid, laboratory markers of severity decreased significantly in the group that received MTP, CRP 2.85 (2.3-3.8) vs 7.2 (5.4-9.8), (p-value < 0.0001), D-dimer 691 (612-847) vs 1083 (740-1565) (p-value = 0.04) and DHL 273 (244-289) vs 355 (270.6-422) (p-value = 0.01). After starting the corticosteroid, transfer to the intensive care unit (4.8% vs. 14.4%) and mortality (9,5% vs. 17.1%) was lower in the group that received MTP. Recovery time was shorter in patients treated with MTP, three days (3-4) vs. DXM 6 days (5-8) (p-value < 0.0001). At 30-day follow-up, 88 (92.6%) were alive in MTP vs 58 (63.1%) of those who received dexamethasone.ConclusionsIn this study, the treatment of severe Covid-19 Pneumonia with high-dose methylprednisolone for three days followed by oral prednisone for 14 days, compared with 6 mg dexamethasone for 7 to 10 days, statistically significantly decreased the recovery time, the need for transfer to intensive care and the severity markers C-reactive protein (CRP), D-dimer and LDH. Randomized controlled studies with methylprednisolone are required to corroborate its effect, and studies in a population hospitalized in intensive care wards.

Project description: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 disparities with inflammatory markers and association of methylprednisolone to in hospital survival.MethodsThis 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.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. 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.ConclusionRacial/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.

Project description:ImportanceSerum ferritin, an acute phase marker of inflammation, has several physiologic functions, including limiting intracellular oxidative stress. Whether the effectiveness of corticosteroids differs according to serum ferritin level in COVID-19 has not been reported.ObjectiveTo examine the association between admission serum ferritin level and methylprednisolone treatment outcomes in nonintubated patients with severe COVID-19.Design, setting, and participantsThis retrospective cohort study included patients with severe COVID-19 admitted to an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020, receiving high-flow oxygen therapy (fraction of inspired oxygen, ≥50%). The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Patients were followed up for 28 days. Data were analyzed from December 19, 2020, to July 22, 2021.ExposuresSystemic methylprednisolone administered per the discretion of the treating physician.Main outcomes and measuresThe primary outcome was mortality, and the secondary outcome was a composite of death or mechanical ventilation at 28 days.ResultsAmong 380 patients with available ferritin data (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 250 [65.8%] men; 310 White patients [81.6%]; 47 Black patients [12.4%]; 23 Asian patients [6.1%]), 142 patients (37.4%) received methylprednisolone (median [IQR] daily dose, 160 [120-240] mg). Ferritin levels were similar in patients who received methylprednisolone vs those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). In weighted analyses using tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1322-13 418 ng/mL), methylprednisolone was associated with lower mortality in patients with ferritin in the upper tertile (HR, 0.16; 95% CI, 0.06-0.45) and higher mortality in those with ferritin in the middle (HR, 2.46; 95% CI, 1.15-5.28) and lower (HR, 2.43; 95% CI, 1.13-5.22) tertiles (P for interaction < .001). Composite end point rates were lower with methylprednisolone in patients with ferritin in the upper tertile (HR, 0.45; 95% CI, 0.25-0.80) but not in those with ferritin in the middle (HR, 0.83; 95% CI, 0.50-1.39) and lower (HR, 0.89; 95% CI, 0.51-1.55) tertiles (P for interaction = .11).Conclusions and relevanceIn this cohort study of nonintubated patients with severe COVID-19, methylprednisolone was associated with improved clinical outcomes only among patients with admission ferritin in the upper tertile of values.

Project description:Background: The emerging coronavirus disease 2019 (COVID-19) has become a serious public health concern with a high number of fatalities. It is unclear whether corticosteroids could be a candidate for an early intervention strategy for patients with COVID-19. Methods: In this retrospective cohort study, we analyzed data from 28 corticosteroid-treated patients with non-severe but advanced COVID-19, in which short-course and low-dose corticosteroids were administered because of unremitting or worsening clinical conditions during hospitalization. To compare the effect of corticosteroids on viral clearance, 44 corticosteroid-untreated patients were included as controls. Results: At the time of admission, corticosteroid-treated patients (n = 28) had a more advanced baseline illness compared with corticosteroid-untreated patients (n = 44), as reflected by poorer blood laboratory parameters (lymphocytes, C-reactive protein, and lactate dehydrogenase) and more extensive chest computed tomography (CT) abnormalities. Corticosteroids were given because of radiological evidence of pneumonia progression (26/28) and/or unremitting fever (22/28) after admission. The median time from illness onset to corticosteroid treatment was 9 days (IQR, 7-10). The median duration and accumulated dose of corticosteroid treatment were 4.5 days [interquartile range (IQR), 3-5] and 140 mg of methylprednisolone (IQR, 120-200). Intravenous immunoglobulin (20 g per day for 3-5 days) was co-administered with corticosteroids. With the corticosteroid treatment, all patients achieved an abatement of fever within 1 day, and 78.6% (22/28) of the patients achieved radiological remission when evaluated about 3 days later. Only one (3.6%) patient progressed to severe COVID-19, and all patients recovered and were discharged without any sequela. The median time from illness onset to viral clearance was similar, as compared with 44 corticosteroid-untreated patients with relatively milder disease [18 (IQR 14.3-23.5) days vs. 17 (IQR, 12-20) days, p = 0.252]. When adjusted for age, sex, underlying comorbidities, baseline blood laboratory parameters, viral load, and chest radiological findings, the causal hazard ratio of corticosteroid treatment for the viral clearance was 0.79 (95%CI, 0.48-1.30, p = 0.34). Conclusion: Short-course and low-dose applications of corticosteroids, when co-administered with intravenous immunoglobulin, in non-severe COVID-19 patients during the stage of clinical deterioration may possibly prevent disease progression, while having a negligible impact on the viral clearance.

Dataset Information

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

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Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

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