Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial

Abstract

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days.Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical–radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit.Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission.Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis.Trial Registration:ClinicalTrials.gov, Identifier: NCT04343729.

Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis

“…This implies that in COVID-19 patients, high levels of IL-6 (> 5.186 pg/ml) could be detected. Such evidence of an increase in levels of IL-6 is also associated with long COVID-19, which is defined after the time window of four weeks (≥ 28 days) post infection [ 13 , 31 – 36 ].

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“…Increased levels of IL-6 were found to be significantly associated with adverse clinical COVID-19 outcomes such as ICU admission, acute respiratory distress syndrome (ARDS), and death. In addition, patients with such complicated forms of COVID-19 had nearly threefold higher serum IL-6 levels than those with noncomplicated disease [ 34 – 36 ].…”

The evidence from clinical trials on Gout medicines effect on COVID‐19: A protocol for systematic review and meta‐analysis

“…Some studies have investigated the efficacy of colchicine (Absalón‐Aguilar et al, 2022 ; Akkaif, Ng, et al, 2021 ; Deftereos et al, 2020 ), and others have tested the impact of XOIs like allopurinol and COX enzyme inhibitors on COVID‐19 patients (Al‐Kuraishy et al, 2022 ), and one study has found that Probenecid has potential clinical benefits in the management of COVID‐19 (Murray et al, 2021 ). Corticosteroid drugs (methylprednisolone and prednisolone) effect on the severity of the disease was also investigated in a few clinical trials because of their immunosuppressant effect (Barros et al, 2021 ; Bitar & Sulaiman, 2022b ; Ghanei et al, 2021 ).…”

AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants

“… 124 In a small RCT in patients with clinical-radiological suspicion of COVID-19 and requirement of oxygen support, a short course of methylprednisolone was shown to improve pulmonary function at day 120. 130 Furthermore, in COVID-19 patients with interstitial lung disease, the application of prednisolone was reported to be beneficial with regard to prevention of pulmonary fibrosis with permanent functional deficit. 131 In a small observational study, systemic corticosteroids administered during the acute phase of COVID-19 were associated with reduced symptoms and better quality of life one year after initial admission for COVID-19.…”