Clinical outcomes of intravenous immunoglobulin therapy in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study

Abstract

Background Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established. Methods We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis. Results Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98–6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group. Conclusion IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.

Intravenous immunoglobulin (IVIg) therapy in hospitalised adult COVID‐19 patients: A systematic review and meta‐analysis

“…Studies' characteristics can be seen in Table 1 . From the 13 included studies, 7 were retrospective cohort studies 30 , 31 , 32 , 33 , 34 , 35 , 36 and 6 were prospective studies. 13 , 37 , 38 , 39 , 40 , 41 From the 6 prospective studies, 2 were randomised placebo controlled double‐blind trials, 2 randomised open‐label trials, 1 was a randomised placebo controlled open label trial and 1 was a non‐randomised open‐label prospective study.…”

Intravenous IgM-enriched immunoglobulins in critical COVID-19: a multicentre propensity-weighted cohort study

“…Furthermore, a recent meta-analysis performed by Xiang and colleagues confirmed the clinical efficacy of IVIGs by showing a favourable impact on survival in critically ill COVID-19 patients [ 28 ]. Nevertheless, the existing literature on IVIGs in COVID-19 is still controversial, which can be mainly explained by the high degree of heterogeneity in disease severity, different disease stages, small cohorts and a lack of standardized treatment regimens across the different studies [ 19 , 29 ]. In this context, a large randomized controlled trial could not demonstrate any benefit on outcome, but even a trend towards an increased frequency of serious adverse events [ 19 ].…”

“…This fact becomes particularly important because several other studies focused exclusively on patients already receiving mechanical ventilation at the start of IVIG treatment, thus focusing on later stages of the disease. In those studies, no clear evidence exists that IVIGs were effective in preventing disease progression or having a beneficial impact on survival [ 19 , 20 , 29 ]. In particular, a large randomized controlled trial from France showed no improved clinical outcome at day 28 by using IVIGs in patients already receiving mechanical ventilation [ 19 ].…”

Nebulized fentanyl for respiratory symptoms in patients with COVID-19 (ventanyl trial)

“…[ 1 – 3 ] Angiotensin-converting enzyme-2 is normally secreted in upper and lower respiratory epithelial cells; thus, angiotensin-converting enzyme-2 stimulation in COVID-19 infection will significantly surge pro-inflammatory mediators and mucosal secretions, leading to dyspnea (breathlessness), cough, and throat pain. [ 4 , 5 ]…”

“…[1][2][3] Angiotensin-converting enzyme-2 is normally secreted in upper and lower respiratory epithelial cells; thus, angiotensin-converting enzyme-2 stimulation in COVID-19 infection will significantly surge pro-inflammatory mediators and mucosal secretions, leading to dyspnea (breathlessness), cough, and throat pain. [4,5] This protein also acts as a pro-inflammatory mediator, which contributes to increased respiratory secretions in respiratory infections, and some of the other symptoms, predominantly, dyspnea, cough, and throat pain. [6,7] These symptoms variably respond to medical interventions such as oxygen therapy, oral opiates, ipratropium bromide and salbutamol nebulizers.…”