Intravenous Immunoglobulin Plus Methylprednisolone Mitigate Respiratory Morbidity in Coronavirus Disease 2019

Abstract

Objectives: Dysregulated neutrophil and platelet interactions mediate immunothrombosis and cause lung injury in coronavirus disease 2019. IV immunoglobulin modulates neutrophil activation through FcγRIII binding. We hypothesized that early therapy with IV immunoglobulin would abrogate immunothrombosis and improve oxygenation and reduce progression to mechanical ventilation in coronavirus disease 2019 pneumonia. Design: Prospective randomized open label. Setting: Inpatient hospital. Patients and Intervention: Hypoxic subjects with coronavirus disease 2019 pneumonia were randomized 1:1 to receive standard of care plus IV immunoglobulin 0.5 g/kg/d with methylprednisolone 40 mg 30 minutes before infusion for 3 days versus standard of care alone. Main Results: Sixteen subjects received IV immunoglobulin and 17 standard of care. Median ages were 51 and 58 years for standard of care and IV immunoglobulin, respectively. Acute Physiology and Chronic Health Evaluation II and Charlson comorbidity scores were similar for IV immunoglobulin and standard of care. Seven standard of care versus two IV immunoglobulin subjects required mechanical ventilation (p = 0.12, Fisher exact test). Among subjects with A-a gradient of greater than 200 mm Hg at enrollment, the IV immunoglobulin group showed: 1) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p = 0.038 Fisher exact test), 2) shorter median hospital length of stay (11 vs 19 d, p = 0.01 Mann Whitney U test), 3) shorter median ICU stay (2.5 vs 12.5 d, p = 0.006 Mann Whitey U test), and 4) greater improvement in Pao 2/Fio 2 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 standard of care. Pao 2/Fio 2 improvement at day 7 was significantly less for the standard of care patients who received glucocorticoid therapy than those in the IV immunoglobulin arm (p = 0.0057, Mann Whiney U test). Conclusions: This pilot study showed that IV immunoglobulin significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in coronavirus disease 2019 patients with A-a gradient greater than 200 mm Hg. A phase 3 multicenter randomized double-blinded clinical trial is under way to validate these findings.

Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan to Hospitalized COVID-19 Patients with Mild Hypoxemia

“…This study was performed in accordance with the Declaration of Helsinki. The study design, process of local IRB approval and adherence to the requirements obtaining an informed consent are similar to our other published studies [ 11 , 12 ].…”

“…Furthermore, given the evolution of SOC therapy over the past year, with the introduction of remdesivir in mid-May 2020 [ 25 – 27 ] and the mainstream adoption of glucocorticoid therapy in mid-June 2020 [ 28 ], it is likely that potentially small signals of ARB clinical benefit that might have been captured in a more treatment-naïve background will be much more difficult to capture in the setting of current treatment paradigms. Other up and coming COVID-19 therapies such as SARS-CoV-2 monoclonal antibodies [ 29 ] and the use of intravenous immunoglobulins [ 11 ] will likely further hamper the study of ARB in the future. Indeed, the limited clinical utility of direct anti-viral therapies is coming to light in larger scale assessments [ 30 ].…”

Intravenous immunoglobulin in COVID-19 associated Guillain–Barré syndrome in pregnancy

“…2 12 COVID-19 is known for its thrombotic complications because of the resulting dysregulated immune response. 15 As such, treatment modalities to address this have been looked into as a potential treatment. Current studies for the use of IVIg in the treatment of COVID-19 showed that its administration offered reduced mortality rates especially if given early.…”

“…Current studies for the use of IVIg in the treatment of COVID-19 showed that its administration offered reduced mortality rates especially if given early. 16 17 Sakoulas and colleagues 15 even mentioned that IVIg can diminish the coagulopathy brought about by COVID-19 in contrast to the initial concern that the treatment will increase thrombotic events in these patients.…”

Use of intravenous immunoglobulin to successfully treat COVID-19 associated encephalitis

“…This supports the evidence of neurotropism of COVID-19. Studies have shown potential use of IVIG in decreasing the respiratory morbidity and mortality in patients with severe COVID-19 infections [5,6] .…”