High-dose steroids for the treatment of severe COVID-19

Abstract

Twelve months after the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, there is no established therapy for patients with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection [1, 2]. Glucocorticosteroids (called steroids thereafter) are the only drug that demonstrated to reduce mortality and the need for invasive mechanical ventilation in hospitalized patients with COVID19 [3, 4]. Accordingly, several national and international guidelines included systemic steroids for the treatment of severe COVID-19 patients [5]. For instance, World Health Organization (WHO) and UK National Institute for Health and Care Excellence strongly recommend low-dose steroids (namely dexamethasone 6 mg/die or equivalent dose) for 7–10 days in adults with severe or critical disease [2, 6]. The optimal dose and duration of steroids treatment are mainly based on a single clinical trial (RECOVERY trial) [7]. However, a conclusive comparison of the efficacy between highand low-dose steroids in COVID-19 patients is not available to date. In other settings, steroids therapy for moderate-to-severe acute respiratory distress syndrome (ARDS) has been recommended at a higher dose [8]. Therefore, the hypothesis that a higher dose could be beneficial, at least in critically ill COVID-19 patients, deserves to be explored. In this case series, we reported clinical characteristics, outcome, and side effects of a small population of patients with critical COVID-19, treated with a high-dose steroids (methylprednisolone equivalent ≥ 2 mg/kg/day) at Careggi University Hospital, Florence, Italy, during the period February 25–April 25, 2020, in three internal medicine and one infectious diseases unit. Inclusion criteria were: (1) diagnosis of COVID-19 confirmed by at least one positive result of real-time polymerase chain reaction (RT-PCR) in a diagnostic specimen (nasopharyngeal swab, sputum, broncho-alveolar lavage); (2) treatment with at least one dose of intravenous high-dose steroids, defined as methylprednisolone equivalent ≥ 2 mg/ kg/day; (3) oxygenation impairment consistent with partial pressure to fractional inspired oxygen ratio (PaO2/FiO2) less than 200 mmHg, before the administration of high-dose steroids. An improved patient was defined as a discharged patient with no need for supplementary oxygen, irrespectively from the monitoring RT-PCR results. Viral clearance was defined as two negative result at RTPCR for SARS-CoV-2 in a nasopharyngeal swab. Descriptive analysis was employed to illustrate population characteristics. Data collection was approved by the local Ethics Committee (17104_oss). The study was performed following the ethical principles of the Declaration of Helsinki and with the International Conference on Harmonization Good Clinical Practice guidelines. Overall, we evaluated 397 patients. Of them, 95 (23.9%) were treated with steroids, but only 14 (3.5%) patients received a high-dose steroids (as for the inclusions criteria); 1 patient was excluded from the analysis because of the PaO2/FiO2 above 200 mmHg. Thus, we included 13 patients. The median age was 76 years (IQR 62–83), 7 (53.8%) were male. The median Charlson comorbidity index (CCI) was 4 (IQR 3–4), and 4 of them had a do-not-resuscitate (DNR) status, according to the medical condition. The median PaO2/FiO2 at the hospitalization and before starting high-dose steroids was 229 mmHg (IQR 134–293) and 98 mmHg (IQR 61–138), respectively (Table 1). Eleven patients had bilateral pulmonary infiltrates, demonstrated by chest radiography and/or high-resolution Members of “For the COCORA Working Group” are listed in Acknowledgement section.