Intravenous immunoglobulin to dampen covid-induced cell damage and hyperinflammation (Kan intravenöst immunglobulin dämpa cellskada och inflammation och förbättra prognosen vid svår covid-19?)

Compromised oxygen diffusion and thromboembolic events are major causes of death in covid-19. The mechanisms leading to lung damage and thrombosis in covid-19 are unknown. Blood analysis reveals markers of inflammation, cell damage and activation of the coagulation system. Hypothesis: We propose that IgG antibodies binding to viral glycoproteins exposed on lung epithelial cells and blood vessel endothelium elicit complement activation and/or ADCC (antibody-dependent cell-mediated cytotoxicity) by Fc-bearing effector cells, causing necrosis and thrombus formation.We further propose that intravenous immunoglobulin, IVIG, will counteract IgG-driven inflammation and reduce alveolar damage and thromboembolism in severe covid-19.Proposed study: We will perform a randomized placebo-controlled study (RCT) comprising 48 (24 + 24) patients. Circulating immune effector cells and markers of inflammation, coagulopathy and cell damage will be measured in blood samples before and after treatment, and in 12 non-covid reference idividuals, included for comparison.Importance: We expect to a) identify mechanisms in involved in lung damage and thromboembolism in covid-19 b) define the clinical response to IVIG treatment and, if beneficial, identify the involved mechanisms for the clinical effect. Infektionsmedicin, Immunologi inom det medicinska området, Mikrobiologi inom det medicinska området