Intravenous Immunoglobulin (IVIG) Significantly Reduces Respiratory Morbidity in COVID-19 Pneumonia: A Prospective Randomized Trial

Abstract

Background. Interventions mitigating progression to mechanical ventilation in COVID-19 would markedly improve outcome and reduce healthcare utilization. We hypothesized that immunomodulation with IVIG would improve oxygenation and reduce length of hospital stay and progression to mechanical ventilation in COVID-19 pneumonia. Methods. Patients with COVID-19 were randomized 1:1 to prospectively receive standard of care (SOC) plus intravenous immunoglobulin (IVIG) 0.5 g/kg/day x 3 days with methylprednisolone 40 mg 30 minutes before infusion versus SOC alone. Results. 16 subjects received IVIG plus SOC and 17 SOC alone. The median age was 51 years for SOC and 58 years for IVIG. APACHE II scores and Charlson comorbidity indices were similar for IVIG and SOC (median 7.5 vs 7 and 2 for both, respectively). Seven SOC versus 2 IVIG subjects required mechanical ventilation (p=0.12, Fisher exact test). Among subjects with A-a gradient of >200 mm Hg at enrollment, the IVIG group showed i) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p=0.038 Fisher exact test), ii) shorter median hospital length of stay (11 vs 19 days, p=0.01 Mann Whitney U), iii) shorter median ICU stay (2.5 vs 12.5 days, p=0.006 Mann Whitey U), and iv) greater improvement in PaO2/FiO2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44.5 [-115 to +157], p=0.01, Mann Whitney-U test) than SOC. Conclusion. This pilot prospective randomized study comprising largely of Latino patients showed that IVIG significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in COVID-19 patients with A-a gradient >200 mm Hg.

How should we use convalescent plasma therapies for the management of COVID-19?

“…38,39 IVIG is already being used in treatment of COVID-19, although evidence of benefit is limited. 38,41 There is preclinical evidence that platelet-derived IgG may be more potent at viral neutralization than plasma IgG, raising the question of whether platelets could be a novel method of delivering passive immune therapy. 42 Therapeutic plasma exchange (TPE) is being studied in trials in critically ill COVID-19 patients; however the rationale for this treatment is not related to passive immunity, but rather removal of potentially harmful circulating cytokines and other molecules, and replacement of protective plasma proteins to maintain microcirculatory flow and prevent vascular leak.…”

Intravenous immunoglobulin immunotherapy for coronavirus disease‐19 (COVID‐19)

“…Currently, data are available from seven reports including the multicentre study of Shao et al that explored IVIG immunotherapy in the management of COVID-19 (Table 1). [5][6][7][8][9][10][11] These studies are mostly case series or retrospective, with an exception of one study that was randomised open-label trial. Although retrospective, data from Shao et al included large number of COVID-19 patients compared to other studies, and hence, data are more reliable.…”

“…6 The only randomised controlled study on IVIG also combined methylprednisolone. 8 In view of the corticosteroid combination, it is difficult to evaluate the therapeutic benefits of IVIG in these trials. Another study combined IVIG with anakinra, a recombinant modified IL-1 receptor antagonist.…”

“…that explored IVIG immunotherapy in the management of COVID‐19 (Table 1). 5–11 These studies are mostly case series or retrospective, with an exception of one study that was randomised open‐label trial. Although retrospective, data from Shao et al .…”

“…Another report documented that short‐term moderate‐dose corticosteroid plus IVIG (20 g day −1 ) might effectively benefit COVID‐19 patients who did not respond to low‐dose therapy (10 g day −1 ) 6 . The only randomised controlled study on IVIG also combined methylprednisolone 8 . In view of the corticosteroid combination, it is difficult to evaluate the therapeutic benefits of IVIG in these trials.…”