Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial

Abstract

Objectives: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. Trial design: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio).

T cell responses in patients with COVID-19

“…Such a precision medicine strategy based on analysis of ‘immune health’ could be used to better tailor the use of immunostimulatory strategies such as thymosin α1 (ref. 25 ) or type I interferon 75 versus immunosuppressive drugs such as tocilizumab 76 – 78 , ruxolitinib 79 or dexamethasone 80 to patients who will receive most benefit. These efforts should be aided by the development of better preclinical models, including human ACE2-expressing mice 81 – 85 .…”

Dexamethasone to combat cytokine storm in COVID-19: Clinical trials and preliminary evidence

“…The high morbidity and mortality associated with SARS-COV-2 infection can be linked to the autoimmune destruction of the lungs that is mediated by the release of a storm of pro-inflammatory cytokines [ 2 ]. In patients with COVID-19, anti-inflammatory drugs such as corticosteroids can be used to reduce the lung damage induced by the cytokine storm [ 3 ]. Dexamethasone, a synthetic corticosteroid, acts as a broad-spectrum immunosuppressor and has a greater activity and longer duration of action than cortisone [ 2 , 4 ].…”

“…As a safer approach, a pulse dose of intravenous dexamethasone can be administered, followed by nebulized triamcinolone (another corticosteroid) to concentrate the effects in the lungs only [ 2 ]. Another strategy to reduce the side effects associated with corticosteroid treatment involves the simultaneous administration of intravenous immunoglobulins and interferon-beta [ 3 ]. A multicenter randomized controlled trial (Identifier: IRCT20120225009124N4) conducted from April 18, 2020 to June 19, 2020 evaluated the therapeutic potential of dexamethasone administered in combination with intravenous immunoglobulin and interferon-beta [ 3 ].…”

COVID-19 pandemic management and the rheumatology patient

“…Public health interventions differed by region and country, but most employed mask use and social distancing with temporary closure of schools and businesses, limitations on large gatherings and guidance to maintain distance from others to help limit respiratory viral transmission. Though some immunomodulatory pharmacological therapies such as remdesivir ( 1 , 2 ) and dexamethasone ( 3 , 4 ) have shown potential benefit to treat patients with Coronavirus disease 2019 (COVID-19), they have not been shown to reduce transmission. In the absence of a therapy or vaccine to decrease the infectious period, further complicated by limited availability of widespread testing and surveillance, and transmission by asymptomatic cases, prevention remains our primary approach to combating this pandemic.…”