Induction of trained immunity by influenza vaccination - impact on COVID-19

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.

A functional genomics approach to understand host genetic regulation ofCOVID-19 severity

Recent genome-wide association studies (GWASs) of COVID-19 patients of European ancestry have identified genetic loci significantly associated with disease severity (1). Here, we employed the detailed clinical, immunological and multi-omics dataset of the Human Functional Genomics Projects (HFGP) to explore the physiological significance of the host genetic variants that influence susceptibility to severe COVID-19. A genomics investigation intersected with functional characterization of individuals with high genetic risk for severe COVID-19 susceptibility identified several major patterns: i. a large impact of genetically determined innate immune responses in COVID-19, with increased susceptibility for severe disease in individuals with defective monocyte-derived cytokine production; ii. genetic susceptibility related to ABO blood groups is probably mediated through the von Willebrand factor (VWF) and endothelial dysfunction. We further validated these identified associations at transcript and protein levels by using independent disease cohorts. These insights allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy. One Sentence summaryIn this study, we explore the physiological significance of the genetic variants associated with COVID-19 severity using detailed clinical, immunological and multi-omics data from large cohorts. Our findings allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy.

Suppressive myeloid cells are a hallmark of severe COVID-19

Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DRhiCD11chi inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DRto monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.

Preliminary Discussion on the Structure of a Novel Housefly Pupae Lectin / 中国生物工程杂志

In order to provide plenty of information about the relationship between its structure and function,the structure of a novel housefly pupae D-galactose binding lectin with the molecular weight 55kDa and immune acitivity was analyzed preliminarily.In the first place,oligosaccharide chain was confirmed to be existed in this kind of novel housefly pupae lectin by the method of gel staining,and then its structure was analyzed with the help of protein sequencing instrument,spectrophotometer color contrast,?-elimination reaction,infrared spectroscopy and atomic force microscopy.This kind lectin was a global-shaped monomer with the diameter 75 nm or so and the protein and oligosaccharide content 97.36% and 2.1% respectively.Peptide chain and oligosaccharide chain was linked by O-glycoside bond with the N-terminal blocked and the sugar ring alpinum type.All above was the reliable theory for further analysis of structure.