Abstract
The rapid spread of SARS-CoV-2 has induced a global pandemic. Severe forms of COVID-19 are characterized by dysregulated immune response and “cytokine storm”. The role of IgG and IgM antibodies in COVID-19 pathology is reasonably well studied, whereas IgA is neglected. To improve clinical outcome of patients, immune modulatory drugs appear to be beneficial. Such drugs include intravenous immunoglobulin preparations, which were successfully tested in severe COVID-19 patients. Here we established a versatile in vitro model to study inflammatory as well as anti-inflammatory processes by therapeutic human immunoglobulins. We dissect the inflammatory activation on neutrophil-like HL60 cells, using an immune complex consisting of latex beads coated with spike protein of SARS-CoV-2 and opsonized with specific immunoglobulins from convalescent plasma. Our data clarifies the role of Fc-receptor-dependent phagocytosis via IgA-FcαRI and IgG-FcγR for COVID-19 disease followed by cytokine release. We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response.
Highlights
Corona virus induced disease 2019 (COVID-19) is a global threat induced by the rapid spread of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Immune complex generation was performed by adding SARS-CoV-2 spike protein specific IgG, IgA, and IgM antibodies from convalescent COVID-19 source plasma (Figure 1A)
The data indicates that all used COVID-19 plasma donations have IgG, IgA, and IgM antibodies in various amounts against the SARS-CoV-2 spike protein
Summary
Corona virus induced disease 2019 (COVID-19) is a global threat induced by the rapid spread of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most infected individuals recovered rapidly, approximately 20% of patients with COVID-19 pneumonia cannot clear the virus and develop severe COVID-19 [1, 2] These patients are characterized by an exhausted immune system with hyperinflammation related severe acute respiratory distress syndrome (ARDS) and so called “cytokine storm” [3, 4]. IgA- and IgM-enriched immunoglobulins are available or are in clinical testing [18, 19] These immunoglobulin therapeutics are known to have benefits in other inflammatory diseases [20,21,22,23]; whether they are advantageous in COVID-19, has yet to be evaluated
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