Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before–After Study (CortiCOVID Study)

Espinosa-Solano, Michelle; Gonzalez-Vergara, Demetrio; Ferrer Galván, Marta; Asensio-Cruz, Maria Isabel; Lomas Cabezas, José Manuel; Cordero Matia, María Elisa; Jara Palomares, Luis José

doi:10.1016/j.opresp.2021.100086

Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before–After Study (CortiCOVID Study)

Espinosa-Solano, Michelle; Gonzalez-Vergara, Demetrio; Ferrer Galván, Marta; Asensio-Cruz, Maria Isabel; Lomas Cabezas, José Manuel; Cordero Matia, María Elisa; Jara Palomares, Luis José

Published: 2021-03-01
Publisher: Elsevier
DOI: 10.1016/j.opresp.2021.100086
Repository: idus.us.es
Language: en

Abstract

Introduction The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5–21.8] days vs. 29 [23–31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode.

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1 Appendices Table of Contents Appendix list of investigators ..................................................................................... 2 Appendix Table A.1 Radiological findings. .................................................................. 3 Appendix Table A.2 Respiratory variables at pulmonologist evaluation ..................... 4 Appendix Table A.3 Laboratory test at evaluation ...................................................... 5 Appendix Table A.4 Antiviral treatment ..................................................................... 6 Appendix Table A.5 Seven-category ordinal scale at 7 and 14 days ............................ 7 2 Appendix list of investigators Clinical Unit of Internal Medicine, Virgen del Rocio Hospital, Sevilla, Spain Rocio Gonzalez-Leon, Veronica Alfaro-Lara, Maximo Bernabeu-Wittel, Aurora Gonzalez-Estrada, Santiago Rodriguez-Suarez, Bosco Baron-Franco, Dolores Nieto- Martin, Juan Delgado, Carlos Hernandez-Quiles, Julia Lanseros-Tenllado, Sonia Gutierrez, Nieves Ramirez-Duque, Manuel Rincon-Gomez, Lourdes Moreno-Gaviño, Fatima Espinosa. Department of Nephrology, Virgen del Rocio Hospital, Sevilla, Spain Alejandro Suarez-Benjumea, Carmen Grande- Cabrerizo, Jose Luis Rocha Department of neurology, Virgen del Rocio Hospital, Sevilla, Spain Macarena Cabrera, Daniel Macias-Garcia, Maria Dolores Jimenez Department of cardiology, Virgen del Rocio Hospital, Sevilla, Spain Nieves Romero-Rodriguez, Almudena Aguilera, Amelia Peña Rodríguez. Department of hepatology, Virgen del Rocio Hospital, Sevilla, Spain Javier Ampuero, Teresa Ferrer. Department of rheumatology, Virgen del Rocio Hospital, Sevilla, Spain Clara Aguilera 3 Appendix Table A.1. Radiological findings. Characteristics All patients (n=24) No Corticosteroids (n=14) Corticosteroids (n=10) Bilateral reticular nodular opacities 10 (41.7 %) 6 (42.9 %) 4 (40 %) Ground-glass opacities 8 (33.3 %) 5 (35.7 %) 3 (30 %) Pleural effusion 1 (4.2 %) 1 (7.1 %) 0 (0 %) Peri-bronchial thickening 1 (4.2 %) 1 (7.1 %) 0 (0 %) Focal consolidation 4 (16.7 %) 1 (7.1 %) 3 (30 %) Pulmonary edema 4 (16.7 %) 1 (7.1 %) 3 (30 %) Venous congestion 5 (20.8 %) 2 (14.3 %) 3 (30 %) Interstitial abnormalities 13 (54.2 %) 8 (57.1 %) 5 (50 %) Atelectasis 1 (4.2 %) 0 (0 %) 1 (10 %) 4 Appendix Table A.2. Respiratory variables at pulmonologist evaluation Characteristics All patients (n=24) No Corticosteroids (n=14) Corticosteroids (n=10) Respiratory rate 20 (20-23.5) 20 (20-22.5) 20 (17-25.3) Spo 2 93.5% (90.3-95%) 94 (91.8-95%) 92 (89.8-96.3) Fio 2 52 (41-60) 60 (47.5-60) 50 (40-56.3) Sato 2 : Fio 2 179 (156-217) 159 (153-202) 189 (173-226) Estimated Pao 2 : Fio 2 214 (195-246) 198 (193-234) 223 (208-254) ROX index 8.3 (7.1-12.4) 8.1 (6.7-12) 9.3 (7.1-13.8) Heart rate 89.5 (81.3-99.5) 90 (84-102.8) 88.5 (80.8-92) Spo 2 : peripheral capillary oxygen saturation; Pao 2 : partial pressure of oxygen. Fio 2 : fraction of inspired oxygen; Pao2: Fio2 ratio was assessed indirectly by Sato2: Fio2 ratio, as previously described1. 5 Appendix Table A.3. Laboratory test at evaluation Characteristics All patients (n=24) No Corticosteroids (n=14) Corticosteroids (n=10) Laboratory test at evaluation Sodium, mEq/L (135-145 mEq/L) 136 (134-138) 138 (136-140) 135 (134-136) White blood cell count, /μL 7.3 (4.5-10.5) 6.2 (4.2-8.5) 9.8 (5.4-10.8) Absolute lymphocyte count, /μL 0.83 (0.54-1.12) 0.83 (0.6-1.11) 0.88 (0.45-1.12) Hemoglobin, g/dL 13.4 (12.5-14.1) 13.5 (12.5-14.2) 13.2 (12.5-14.3) Platelet count, ×103/μL 237 (149-280) 181.5 (130.8-252) 311.5 (175.3-438) Neutrophils, ×109/L 5.52 (3.46-8.81) 5.03 (3.28-6.2) 7.32 (4.67-9.88) D-dimer, ng/mL 860 (497.5-1515) 735 (420-1485) 1050 (782.5-1885) Creatinine, mg/dL 0.92 (0.72-1.2) 0.95 (0.73-1.27) 0.9 (0.7-1.1) Total bilirubin, mg/dL 0.58 (0.39-1.14) 0.52 (0.31-1.07) 0.6 (0.42-1.2) Aspartate aminotransferase, U/L (0-30) 45 (28-67) 55 (41-87.8) 27 (21.5-44) Alanine aminotransferase, U/L (20-40) 33 (29-54) 44 (29-62.3) 29 (22.5-45) Ferritine 1473.4 (764.6-2037.5) 1847.4 (1442.8-3446.8) 1217 (635.8-1769.3) C-reactive protein, mg/L 219.3 (89.4-281.2) 238.7 (110.2-271.2) 132 (84.9-333.6) Fibrinogen mg/dL 5.6 (4.7-7.4) 5.1 (4.5-7.6) 6.8 (4.7-8.2) Prothrombin Time (seconds) 13.8 (12.3-22) 14.1 (12.2-24.6) 13.4 (13.1-13.8) 6 Appendix Table A.4. Antiviral treatment Characteristics All patients (n=24) No Corticosteroids (n=14) Corticosteroids (n=10) Lopinavir/Ritonavir 24 (100 %) 14 (100 %) 10 (100 %) Hidroxicloroquin 24 (100 %) 14 (100 %) 10 (100 %) IFNB1b 20 (83.3 % 12 (85.7 %) 8 (80 %) Tocilizumab 15 (62.5 %) 12 (85.7 %) 3 (30 %) Azitromicin 19 (79.2 %) 13 (92.9 %) 6 (60 %) 7 Appendix Table A.5. Seven-category ordinal scale at 7 and 14 days Characteristics All patients (n=24) No Corticosteroid s (n=14) Corticosteroids (n=10) SEVEN CATEGORY SCALE 7 DAYS (N, %) 1. Not hospitalized with resumption of normal activities. 0 0 0 2. Not hospitalized, but unable to resume normal activities. 2 (8.3 %) 0 2 (20 %) 3. Hospitalized, not requiring supplemental oxygen. 0 0 0 4. Hospitalized, requiring supplemental oxygen. 3 (12.5 %) 1 (7.1 %) 2 (20%) 5. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 4 (16.7 %) 0 4 (40%) 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both. 14 (58.3 %) 12 (85.7 5) 2 (20%) 7. Death. 1 (4.2 %) 1 (7.1 %) 0 SEVEN CATEGORY SCALE 14 DAYS (N, %) 1. Not hospitalized with resumption of normal activities. 1 (4.2 %) 0 1 (10 %) 2. Not hospitalized, but unable to resume normal activities. 5 (20.8%) 1 (7.1%) 4 (40%) 3. Hospitalized, not requiring supplemental oxygen. 1 (4.2%) 0 1 (10%) 4. Hospitalized, requiring supplemental oxygen. 4 (16.7%) 2 (14.3 %) 2 (20 %) 5. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both. 2 (8.3%) 2 (14.3 %) 0 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both. 8 (33.3%) 6 (42.9 %) 2 (20 %) 7. Death. 3 (12.5%) 3 (21.4%) 8 REFERENCE 1 Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB. Comparison of the SpO2/FIO2 Ratio and the PaO2/FIO2 Ratio in Patients With Acute Lung Injury or ARDS. Chest 2007 Aug;132(2):410-7. CHEST, Volume 132, Issue 2, 410 - 417