HLA Genotypes in Patients with Infection Caused by Different Strains of SARS-CoV-2.

The aggressive infectious nature of SARS-CoV-2, its rapid spread, and the emergence of mutations necessitate investigation of factors contributing to differences in SARS-CoV-2 susceptibility and severity. The role of genetic variations in the human HLA continues to be studied in various populations in terms of both its effect on morbidity and clinical manifestation of illness. The study included 484 COVID-19 convalescents (northwest Russia residents of St. Petersburg). Cases in which the responsible strain was determined were divided in two subgroups: group 1 (n = 231) had illness caused by genovariants unrelated to variant of concern (VOC) strains; and group 2 (n = 80) had illness caused by the delta (B.1.617.2) VOC; and a control group (n = 1456). DNA typing (HLA-A, B, DRB1) was performed at the basic resolution level. HLA-A*02 was associated with protection against infection caused by non-VOC SARS-CoV-2 genetic variants only but not against infection caused by delta strains. HLA-A*03 was associated with protection against infection caused by delta strains; and allele groups associated with infection by delta strains were HLA-A*30, B*49, and B*57. Thus, in northwest Russia, HLA-A*02 was associated with protection against infection caused by non-VOC SARS-CoV-2 genetic variants but not against delta viral strains. HLA-A*03 was associated with a reduced risk of infection by delta SARS-CoV-2 strains. HLA-A*30, HLA-B*49, and HLA-B*57 allele groups were predisposing factors for infection by delta (B.1.617.2) strains.

A novel method for multiplex protein biomarker analysis of human serum using quantitative MALDI mass spectrometry.

In this work, we have extended our previously proposed approach for determining protein concentrations in human serum (using MALDI-TOF mass spectrometry) to include simultaneous analysis of several proteins associated with acute inflammation (alpha-2-macroglobulin, fetuin-A, serum amyloid A1). This technique can be used to diagnose systemic inflammation and provides results in 4-5 h. The developed approach was verified using standard immunological methods (ELISA). Samples from 87 individuals, in specific groups, were used for testing and validation: control; inflammatory soft tissue disease accompanied by sepsis; influenza A infection; or COVID-19. The feasibility of differentiating patient groups with the aforementioned conditions was analyzed using a combination of the inflammatory markers described. For fetuin-A and serum amyloid A1, diagnostically significant concentration ranges were established.

Quench me if you can: Alpha-2-macroglobulin trypsin complexes enable serum biomarker analysis by MALDI mass spectrometry.

One of the main functions of alpha-2-macroglobulin (A2M) in human blood serum is the binding of all classes of protease. It is known that trypsin, after such interaction, possesses modified proteolytic activity. Trypsin first hydrolyzes two bonds in A2M's 'bait region', and the peptide 705VGFYESDVMGR715 is released from A2M. In this work, specifics of the A2M-trypsin interaction were used to determine A2M concentration directly in human blood serum using MALDI mass-spectrometry. Following exogenous addition of trypsin to human blood serum in vitro, the concentration of the VGFYESDVMGR peptide was measured, using its isotopically-labeled analogue (18O), and A2M concentration was calculated. The optimized mass spectrometric approach was verified using a standard method for A2M concentration determination (ELISA) and the relevant statistical analysis methods. It was also shown that trypsin's modified proteolytic activity in the presence of serum A2M can be used to analyze other serum proteins, including potential biomarkers of pathological processes. Thus, this work describes a promising approach to serum biomarker analysis that can be technically extended in several useful directions.

The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections.

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.