Intravenous immunoglobulins at the crossroad of autoimmunity and viral infections

Intravenous immunoglobulins (IVIG) are blood preparations pooled from the plasma of donors that have been first employed as replacement therapy in immunodeficiency. IVIG interact at multiple levels with the different components of the immune system and exert their activity against infections. Passive immunotherapy includes convalescent plasma from subjects who have recovered from infection, hyperimmune globulin formulations with a high titer of neutralizing antibodies, and monoclonal antibodies (mAbs). IVIG are used for the prevention and treatment of several infections, especially in immunocompromised patients, or in case of a poorly responsive immune system. The evolution of IVIG from a source of passive immunity to a powerful immunomodulatory/anti-inflammatory agent results in extensive applications in autoimmune diseases. IVIG composition depends on the antibodies of the donor population and the alterations of protein structure due to the processing of plasma. The anti-viral and anti-inflammatory activity of IVIG has led us to think that they may represent a useful therapeutic tool even in COVID-19. The human origin of IVIG carries specific criticalities including risks of blood products, supply, and elevated costs. IVIG can be useful in critically ill patients, as well as early empirical treatment. To date, the need for further well-designed studies stating protocols and the efficacy/tolerability profile of IVIG and convalescent plasma in selected situations are awaited.