On the Use of Immunoglobulins for Pre-exposure Prophylaxis Against COVID-19 in Immunocompromised Patients

Daniele Focosi,1 Massimo Franchini,2 Arturo Casadevall3 1North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy; 2Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantua, Italy; 3Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USACorrespondence: Daniele Focosi, Email daniele.focosi@gmail.comAbstract: COVID-19 remains a cause of significant mortality and morbidity for immunocompromised patients. In the current absence of effective monoclonal antibodies to SARS-CoV-2, standard commercial intravenous/subcutaneous immunoglobulin (IVIG/SCIG) lots provide an option for passive immunotherapy since these now consistently contain SARS-CoV-2-reactive antibodies. Strong mechanistic considerations and emerging observational data support the use of IVIG/SCIG as a biologically plausible option for COVID-19 pre-exposure prophylaxis (PreEP) in immunocompromised patients. In this review, we summarize the supporting evidence available and consider optimal use cases. Neutralization capacity against Omicron lineages is consistently reduced and highly variable between lots, and there is an intrinsic several-month lag between donor immunity and product infusion. The available information in literature sources consistently reflects the use of standard replacement dosing of IVIG/SCIG and does not systematically analyze COVID-19-specific safety or outcomes with dose intensification. While the available evidence suggests that IVIG/SCIG may be effective in PreEP, without dedicated randomized or well-controlled human trials, the magnitude of clinical benefit from this intervention remains uncertain, especially against contemporary Omicron sublineages.Keywords: neutralizing antibodies, immunoglobulins, spike, treatment-emergent resistance