Total plasma N-glycomic signature of SARS-CoV-2 infection

Total plasma protein N-glycosylation (TPNG) changes are a hallmark of many diseases. Here, we analyzed the TPNG of 169 COVID-19 patients and 12 healthy controls, using mass spectrometry, resulting in the relative quantification of 85 N-glycans. We found a COVID-19 N-glycomic signature, with 59 glycans differing between patients and controls, many of them additionally differentiating between severe and mild COVID-19. Tri- and tetra-antennary N-glycans were increased in patients, showing additionally elevated levels of antennary α2,6-sialylation. Conversely, bisection of di-antennary, core-fucosylated, nonsialylated glycans was low in COVID-19, particularly in severe cases, potentially driven by the previously observed low levels of bisection on antibodies of severely diseased COVID-19 patients. These glycomic changes point toward systemic changes in the blood glycoproteome, particularly involvement of acute-phase proteins, immunoglobulins and the complement cascade. Further research is needed to dissect glycosylation changes in a protein- and site-specific way to obtain specific functional leads.