Esther Maguilla Rosado

This work aimed to investigate interactions between antibody-opsonized SARS-CoV-2 and monocytes enriched from human peripheral blood mononuclear cells (PBMC) to determine whether antibody dependent enhancement might contribute to the pathophysiology of COVID-19. Pre-incubation of SARS-CoV-2 with sera from hospitalized COVID-19 patients led to significantly increased virus uptake and viral replication in monocytes. Remarkably, SARS-CoV-2 pre-incubated with sera from patients with severe COVID-19 but not those with mild disease or post vaccination strongly increased IL-6 secretion by monocytes. Antibody dependent viral uptake was partially inhibited by monoclonal anti-FcγRIIa antibody whereas IL-6 secretion was completely abolished. FcγRIIa preferentially binds IgG2, and sera from patients with severe COVID-19 contained lower IgG2 levels as compared to mild COVID-19 cases whereas IgG1 levels were increased. These data suggests that FcγRIIa-mediated binding of antibody-opsonized SARS-CoV-2 critically impacts monocytic inflammatory cytokine release and COVID-19 pathophysiology.

(1) Background: Automated blood culture headspace analysis for the detection of volatile organic compounds of microbial origin (mVOC) could be a non-invasive method for bedside rapid pathogen identification. We investigated whether analyzing the gaseous headspace of blood culture (BC) bottles through gas chromatography-ion mobility spectrometry (GC-IMS) enables differentiation of infected and non-infected; (2) Methods: BC were gained out of a rabbit model, with sepsis induced by intravenous administration of E. coli (EC group; n = 6) and control group (n = 6) receiving sterile LB medium intravenously. After 10 h, a pair of blood cultures was obtained and incubated for 36 h. The headspace from aerobic and anaerobic BC was sampled every two hours using an autosampler and analyzed using a GC-IMS device. MALDI-TOF MS was performed to confirm or exclude microbial growth in BCs; (3) Results: Signal intensities (SI) of 113 mVOC peak regions were statistically analyzed. In 24 regions, the SI trends differed between the groups and were considered to be useful for differentiation. The principal component analysis showed differentiation between EC and control group after 6 h, with 62.2% of the data variance described by the principal components 1 and 2. Single peak regions, for example peak region P_15, show significant SI differences after 6 h in the anaerobic environment (p < 0.001) and after 8 h in the aerobic environment (p < 0.001); (4) Conclusions: The results are promising and warrant further evaluation in studies with an extended microbial panel and indications concerning its transferability to human samples.