How IvIg Can Mitigate Covid-19 Disease: A Symmetrical Immune Network Model.

In this report we provide a hypothesis of how intravenous immunoglobulin (IvIg) (pooled therapeutic normal IgG) mitigates the severe disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease is caused by an overreaction of the innate immune system producing a cytokine storm and inflicting multiple organ damage. Our interpretation of IvIg therapy hinges on a recent analysis of the immune dysregulation in Covid-19 infection. Previous infections with common cold coronavirus induce suppressor memory B cells that inhibit an immune response to Covid-19. The repertoire of natural antibodies (IvIg) contains suppressing antibodies in a symmetrically balanced network structure. When this repertoire interacts with the imbalanced network in the infected patient, it can neutralize the suppression of an antibody response against Covid-19. The described scenario for IvIg in Covid-19 infection may also apply in the therapy of autoimmune diseases.

A Novel Hypothesis for Original Antigenic Sin in the Severe Disease of SARS-CoV-2 Infection.

In this hypothesis, we address the biological/immunological pathway leading to severe disease or death after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune response is described with "original antigenic sin" (OAS) whereby previous infections influence the response to future virus encounters. We cite evidence for OAS-induced immunopathology in HIV-1 disease. We hypothesize that similar immune abnormalities can occur after infection with SARS-CoV-2. This hypothesis is supported by recent analysis of the antibodies in infected patients demonstrating serological and B cell abnormalities. The concept of symmetrical clonal regulation developed earlier for the immune network illustrates the pathway suggested by our hypothesis and may be helpful to develop strategies avoiding severe coronavirus disease 2019.