{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:43:32Z","timestamp":1759970612782,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: A COVID-19 model with a viral first-week phase and an inflammatory second phase has been proposed. It has been suggested that immunosuppressive treatment in the first week is harmful. This study aimed to analyze the potential damage of corticosteroids (CS) administered in the first week of COVID-19. Materials and Methods: This study was performed on a large cohort of consecutive COVID-19 patients admitted to Bellvitge University Hospital (Barcelona, Spain) from March 2020 to April 2021. Patients diagnosed with COVID-19 who were treated with 6 mg of dexamethasone a day for 10 days, and whose initiation of administration occurred within the first 2 weeks from symptom onset were included. We divided the cohort into the following two groups: patients for whom CS were initiated within the first 7 days after symptom onset vs. patients for whom CS were initiated between days 8 and 14. The degree of analytical inflammation (based on lymphocyte count, C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer) upon admission was taken into account. The primary outcome was in-hospital mortality. Results: A total of 581 patients met the inclusion criteria. The results included, as follows: differences in age at baseline between groups (70.8 years old vs. 62.7, p &lt; 0.001); moderate-to-severe dependency (11.9% vs. 4.2%, p = 0.003); the lymphocyte count (840 \u00d7 106\/L vs. 900, p = 0.033); D-dimer (400 ng\/mL vs. 309, p &lt; 0.001); and PaO2\/FiO2 (290 vs. 311, p &lt; 0.001). In-hospital mortality in patients who received CS in the first week of symptom onset was higher (29% vs. 12.8%, p &lt; 0.001). The following risk factors were associated with higher in-hospital mortality: age (OR = 1.06, p &lt; 0.001); Charlson index (OR = 1.34, p = 0.001); tachypnea &gt; 20 bpm (OR = 2.58, p &lt; 0.001); \u22653 high-risk criteria of inflammation (OR = 1.94, p = 0.012); and CS onset in the first week (OR = 2.17, p = 0.004). A higher PaO2\/FiO2 (OR = 0.99, p &lt; 0.001) and the use of remdesivir (OR = 0.53, p = 0.021) were identified as protective factors. However, when stratified by analytical inflammation criteria, the onset of CS in the first week did not reach statistical significance. Conclusions: The early administration of CS did not demonstrate a significant detrimental effect. These results highlight the need for a nuanced approach to CS therapy in COVID-19 that carefully weighs the risks and benefits based on individual patient characteristics and the severity of the inflammation.<\/jats:p>","DOI":"10.3390\/medicina61020233","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T11:38:49Z","timestamp":1737977929000},"page":"233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Should the Start of Immunosuppressive Treatment for COVID-19 Rely upon the Degree of Inflammation or the Time from Onset?"],"prefix":"10.3390","volume":"61","author":[{"given":"Jos\u00e9 Mar\u00eda","family":"Mora-Luj\u00e1n","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Parc Sanitari Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abelardo","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-298X","authenticated-orcid":false,"given":"Francesc","family":"Formiga","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9548-1374","authenticated-orcid":false,"given":"Manuel","family":"Rubio-Rivas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jmv.26232","article-title":"The cytokine storm and COVID-19","volume":"93","author":"Hu","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.healun.2020.03.012","article-title":"COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal","volume":"39","author":"Siddiqi","year":"2020","journal-title":"J. Heart Lung Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in Hospitalized Patients with Covid-19","volume":"384","author":"Chappell","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","first-page":"CD014963","article-title":"Systemic corticosteroids for the treatment of COVID-19","volume":"8","author":"Wagner","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2002808","DOI":"10.1183\/13993003.02808-2020","article-title":"Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: Results from a randomised controlled clinical trial","volume":"56","author":"Edalatifard","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1001\/jama.2020.17021","article-title":"Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients with Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial","volume":"324","author":"Tomazini","year":"2020","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2100048","DOI":"10.1183\/13993003.00048-2021","article-title":"Management of hospitalised adults with coronavirus disease 2019 (COVID-19): A European Respiratory Society living guideline","volume":"57","author":"Chalmers","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_8","unstructured":"COVID-19 Treatment Guidelines Panel (2024, October 02). Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/about-the-guidelines\/guidelines-archive."},{"key":"ref_9","unstructured":"Bhimraj, A., Morgan, R., Shumaker, A., Lavergne, V., Baden, L., Cheng, V.C.-C., Edwards, K.M., Gallagher, J.C., Gandhi, R.T., and Muller, W.J. (2021, June 08). Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America Website. Available online: https:\/\/www.idsociety.org\/practice-guideline\/COVID-19-guideline-treatment-and-management."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2201514","DOI":"10.1183\/13993003.01514-2022","article-title":"Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: A randomised controlled trial (MEDEAS)","volume":"61","author":"Salton","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e34738","DOI":"10.1097\/MD.0000000000034738","article-title":"Methylprednisolone or dexamethasone? How should we choose to respond to COVID-19?: A systematic review and meta-analysis of randomized controlled trials","volume":"102","author":"Li","year":"2023","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.chest.2020.10.054","article-title":"Impact of corticosteroids in coronavirus disease 2019 outcomes: Systematic review and meta-analysis","volume":"159","author":"Cano","year":"2021","journal-title":"Chest"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1378\/chest.08-2408","article-title":"Activation and regulation of systemic inflammation in ARDS: Rationale for prolonged glucocorticoid therapy","volume":"136","author":"Meduri","year":"2009","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1007\/s00134-017-4914-x","article-title":"Critical illness-related corticosteroid insufficiency (CIRCI): A narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)","volume":"43","author":"Annane","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2147\/JEP.S484596","article-title":"The Efficacy of Oral\/Intravenous Corticosteroid Use in COVID-19 Patients: A Systematic Review","volume":"16","author":"Adha","year":"2024","journal-title":"J. Exp. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s11739-021-02655-6","article-title":"Timing of corticosteroids impacts mortality in hospitalised COVID-19 patients","volume":"16","author":"Bahl","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1159\/000512063","article-title":"Early use of corticosteroid may prolong SARS-CoV-2 shedding in non-Intensive care unit patients with COVID-19 pneumonia: A Multicenter, Single-Blind, Randomized Control Trial","volume":"100","author":"Tang","year":"2021","journal-title":"Respiration"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1177\/0897190020979608","article-title":"A response to the recommendations for using dexamethasone for the treatment of COVID-19: The dark side of dexamethasone","volume":"34","author":"Salem","year":"2021","journal-title":"J. Pharm. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Spagnuolo, V., Guffanti, M., Galli, L., Poli, A., Querini, P.R., Ripa, M., Clementi, M., Scarpellini, P., Lazzarin, A., and Tresoldi, M. (2020). Viral clearance after early corticosteroid treatment in patients with moderate or severe covid-19. Sci. Rep., 10.","DOI":"10.21203\/rs.3.rs-41021\/v1"},{"key":"ref_20","first-page":"147","article-title":"Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19","volume":"81","author":"Fang","year":"2020","journal-title":"J. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"EVIDoa2200283","DOI":"10.1056\/EVIDoa2200283","article-title":"Meta-Analysis of glucocorticoids for covid-19 patients not receiving oxygen","volume":"2","author":"Covello","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_22","unstructured":"The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group (2020). Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A Meta-analysis. JAMA, 324, 1330\u20131341."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1007\/s10787-023-01251-8","article-title":"Intermediate- to high-dose dexamethasone versus low-dose dexamethasone in patients with COVID-19 requiring respiratory support: A systematic review and meta-analysis of randomized trials","volume":"31","author":"Kow","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10238-024-01405-0","article-title":"Efficacy and safety of glucocorticoids in the treatment of COVID-19: A systematic review and meta-analysis of RCTs","volume":"24","author":"Ye","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mora-Luj\u00e1n, J.M., Tuells, M., Montero, A., Formiga, F., Homs, N.A., Alb\u00e0-Albalate, J., Corbella, X., and Rubio-Rivas, M. (2021). 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. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194465"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijid.2020.09.1486","article-title":"Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness","volume":"101","author":"Ronda","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ofad105","DOI":"10.1093\/ofid\/ofad105","article-title":"Optimal Duration of Systemic Corticosteroids in Coronavirus Disease 2019 Treatment: A Systematic Review and Meta-analysis","volume":"10","author":"Ssentongo","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"He, Q., Wang, C., Wang, Y., Chen, G., Zhou, Y., Wu, Y., and Zhong, M. (2023). Efficacy and safety of glucocorticoids use in patients with COVID-19: A systematic review and network meta analysis. BMC Infect. Dis., 23.","DOI":"10.1186\/s12879-023-08874-w"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rubio-Rivas, M., Corbella, X., Formiga, F., Men\u00e9ndez Fern\u00e1ndez, E., Mart\u00edn Escalante, M.D., Ba\u00f1os Fern\u00e1ndez, I., Arnalich Fern\u00e1ndez, F., Del Corral-Beamonte, E., Lalueza, A., and Parra Virto, A. (2021). Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry. J. Clin. Med., 10.","DOI":"10.3390\/jcm10102214"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s11606-021-07146-0","article-title":"The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers","volume":"37","author":"Montero","year":"2022","journal-title":"J. Gen. Intern. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:25Z","timestamp":1759919845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["medicina61020233"],"URL":"https:\/\/doi.org\/10.3390\/medicina61020233","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}