Seroconversion stages COVID19 into distinct pathophysiological states

Abstract

COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.

A serum proteome signature to predict mortality in severe COVID-19 patients

“…Among others, these included several complement related proteins (which are not statistically differential in our data). Other proteins observed to be significantly differential in the plasma proteomics and SOMAscan analyses of Galbraith et al ( 6 ) include SERPINA3 , SERPINC1 , PLG , and KNG1 , which follow the same trend as in the data of Geyer et al ( 31 Preprint ), Demichev et al ( 8 Preprint ) as well as our work. Overall, our data is in better agreement with the Geyer et al and Demichev et al data sets, but that may also be due to the fact that the classification made by Galbraith et al was based on seroconversion, and thus different from the classifications made by the other groups.…”

“…In the last months, the research efforts on COVID-19 have expanded enormously. In this period, quite a few multi-omics and plasma proteomics studies have appeared studying COVID-19 patients, generating data comparable to ours, but with different research questions and thus also different study designs ( 2 , 5 , 6 , 7 , 8 Preprint , 31 Preprint ). Still, the outcome of these studies and their conclusions can be compared with the data obtained in our cohort (further termed “Ferrara cohort”).…”

“…In addition, relevant to our work, Galbraith et al ( 6 ) reported a very extensive multi-omics study, performing in parallel plasma proteomics by mass spectrometry and SOMAscan assays, cytokine profiling, and immune cell profiling via mass cytometry. They compared 32 controls with 73 COVID-19 positive donors.…”

“…Given the central role of proteins in biological processes as a whole, and in particular in diseases, we applied mass spectrometry–based proteomics to identify protein biomarkers that could discriminate between the COVID-19 patients who recovered and those who did not survive. Several proteomic studies ( 2 , 3 , 4 , 5 ) or even multi-omics studies, including proteomics ( 6 , 7 ), have to date investigated the serum or plasma of COVID-19 patients for the most part comparing a cohort of COVID-19 patients with control subjects (no disease) ( 2 , 3 ). Of special relevance to our work, an extensive study by Demichev et al ( 8 ) has already investigated the temporal aspect of COVID-19 progression in individuals to predict outcome and future disease progression.…”

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

“…As expected in immunocompetent subjects, seroconversion is positively associated with frequency of switched memory B cells, IgM+ memory B cells, CD19+CD27hiIgM-IgD+ c-delta switched memory B cells, and CD19+ CD11c+Tbet+ ABCs, whose percentages are higher in patients with a high seroconversion index vs. patients with a low seroconversion index (Galbraith et al, 2021).…”