Rationale for Polyclonal Intravenous Immunoglobulin Adjunctive Therapy in COVID-19 Patients: Report of a Structured Multidisciplinary Consensus

Abstract

Introduction: Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID-19 and the mechanisms of action of Ig led to the consideration of this adjunctive therapy, including in patients with respiratory failure due to the SARS-CoV-2 infection. This manuscript reports the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID-19. Methods: A panel of multidisciplinary experts defined the clinical phenotypes of COVID-19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. Results: Three different phenotypes of COVID-19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune paralysis (late phase) and patients with sepsis due to a hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panelists considered its use in the late phase and patients with sepsis/septic shock by bacterial superinfection appropriate. Conclusion: As with other immunotherapies, IVIg adjunctive therapy may have a potential role in the management of COVID-19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.

Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study

“…In fact, severe patients with virus infection may get benefit due to the regulated effect of IVIG on host immune response. 20 Systematic inflammatory response syndrome has been widely reported in severe SFTS patients, and they were considered to receive IVIG in real world. 2,9 However, both the followed compensatory anti-inflammatory response syndrome and the influence of IVIG in inactive auto-reactive T-cells increased susceptibility to secondary infection.…”

Special Issue “Pulmonary and Critical Care Practice in the Pandemic of COVID-19”

“…Several other interesting findings were also published in this Special Issue [17][18][19]. As the Guest Editor, I would like to give special thanks to the reviewers for their professional comments and to the JCM team for their robust support.…”

“…Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2), which is responsible for the coronavirus disease 2019 (COVID- 19), has hit the world as a global pandemic at an unparalleled scale [1], causing substantial morbidity and mortality and inflicting unprecedented harm on the economic and health sectors [2]. Therefore, intensive efforts have been made worldwide to develop effective therapies to reduce the risk of severe COVID-19 illness, hospitalizations, and deaths.…”

Benefits of high-dose intravenous immunoglobulin on mortality in patients with severe COVID-19: An updated systematic review and meta-analysis

“…For COVID-19 patients who already progressed to critically ill status, the high-dose IVIg was ineffective, indicating its short therapeutic window ( 48 ). The major challenge in the application of high-dose IVIg or other immunomodulators is to grasp the proper therapeutic window of the hyper-inflammatory stage of SARS-CoV-2 infection ( 5 , 56 – 58 ). Although it is a costly and scarcely available product, the application of high-dose IVIg therapy might be effective among severe COVID-19 patients in clinical prognosis and in the pharmacoeconomic perspective ( 59 ).…”