COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

The ability of red blood cells (RBCs) to transport gases, their lifespan as well as their rheological properties invariably depend on the deformability, hydration, and membrane stability of these cells, which can be measured by Laser optical rotational red cell analyser (Lorrca® Maxsis, RR Mechatronics). The osmoscan mode of Lorrca is currently used in diagnosis of rare anemias in clinical laboratories. However, a broad range of normal values for healthy subjects reduces the sensitivity of this method for diagnosis of mild disease phenotype. In this pilot study, we explored the impact of age and gender of 45 healthy donors, as well as RBC age on the Lorrca indices. Whereas gender did not affect the Lorrca indices in our study, the age donors had a profound effect on the O_hyper parameter. To study the impact of RBC age on the osmoscan parameters, we have isolated low (L)-, medium (M)-, or high (H)- density fractions enriched with young, mature, and senescent RBCs, respectively, and evaluated the influence of RBC age-related properties, such as density, morphology, and redox state, on the osmoscan indices. As before, O_hyper was the most sensitive parameter, dropping markedly with an increase in RBC density and age. Senescence was associated with a decrease in deformability (EI_max) and tolerability to low and high osmolatites (Area). L-fraction was enriched with reticulocytes and cells with high projected area and EMA staining, but also contained a small number of cells small in projected area and most likely, terminally senescent. L-fraction was on average slightly less deformable than mature cells. The cells from the L-fraction produced more oxidants and NO than all other fractions. However, RBCs from the L-fraction contained maximal levels of reduced thiols compared to other fractions. Our study suggests that reference values for O_hyper should be age-stratified, and, most probably, corrected for the average RBC age. Further multi-center study is required to validate these suggestions before implementing them into clinical practice.

The emergence of drug resistant Mycobacterium tuberculosis (MTB) strains has become a global public health problem, while, at the same time, there has been development of new antimicrobial agents. The main goals of this study were to determine new variants associated with drug resistance in MTB and to observe which polymorphisms emerge in MTB genomes after anti-tuberculosis treatment. We performed whole-genome sequencing of 152 MTB isolates including 70 isolates as 32 series of pre- and post-treatment MTB. Based on genotypes and phenotypic drug susceptibility, we conducted phylogenetic convergence-based genome-wide association study (GWAS) with streptomycin-, isoniazid-, rifampicin-, ethambutol-, fluoroquinolones-, and aminoglycosides-resistant MTB against susceptible ones. GWAS revealed statistically significant associations of SNPs within Rv2820c, cyp123 and indels in Rv1269c, Rv1907c, Rv1883c, Rv2407, Rv3785 genes with resistant MTB phenotypes. Comparisons of serial isolates showed that treatment induced different patterns of intra-host evolution. We found indels within Rv1435c and ppsA that were not lineage-specific. In addition, Beijing-specific polymorphisms within Rv0036c, Rv0678, Rv3433c, and dop genes were detected in post-treatment isolates. The appearance of Rv3785 frameshift insertion in 2 post-treatment strains compared to pre-treatment was also observed. We propose that the insertion within Rv3785, which was a GWAS hit, might affect cell wall biosynthesis and probably mediates a compensatory mechanism in response to treatment. These results may shed light on the mechanisms of MTB adaptation to chemotherapy and drug resistance formation.

This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE). Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery (n = 196 vs n = 110; NTC02890121) and an independent validation cohort (n = 30 vs n = 83; NCT02890134) from the European PRECISESADS project. Validated daAAbs were analysed in relation to global and organ-specific disease activity using linear and logistic regression, along with daAAb target pathway enrichment analysis. We validated 89 IgG and 66 IgA daAAbs. IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with a SLE disease activity index 2000 score of ≥10, negatively associated with lupus low disease activity state, and highly prevalent in subgroups with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cutoff for positivity in 53% of patients with central nervous system (CNS) involvement, a prevalence higher than that observed for anti-double-stranded DNA (20%) and 47% of patients with renal activity. A cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, was linked to CNS involvement. IgA anti-FOSL2 was elevated uniquely in patients with musculoskeletal activity. Enriched pathways involving DNA binding and repair showed considerable overlap across manifestations. Novel IgG and IgA autoantibodies, including IgG anti-LIN28A, IgG anti-HMGN5, IgG and IgA anti-IRF5, and IgG and IgA anti-TGIF1 were associated with SLE disease activity and highly abundant across organ manifestations.

Mycobacterium tuberculosis Beijing genotype associated with drug resistance is a growing public health problem worldwide. The aim of this study was the assessment of virulence for C57BL/6 mice after infection by clinical M. tuberculosis strains 267/47 and 120/26, which belong to the modern sublineages B0/W148 and Central Asia outbreak of the Beijing genotype, respectively. The sublineages were identified by the analysis of the strains’ whole-genomes. The strains 267/47 and 120/26 were characterized as agents of pre-extensively drug-resistant (pre-XDR) and multidrug-resistant (MDR) tuberculosis, respectively. Both clinical strains were slow-growing in 7H9 broth compared to the M. tuberculosis H37Rv strain. The survival rates of C57BL/6 mice infected by 267/47, 120/26, and H37Rv on the 150th day postinfection were 10%, 40%, and 70%, respectively. Mycobacterial load in the lungs, spleen, and liver was higher and histopathological changes were more expressed for mice infected by the 267/47 strain compared to those infected by the 120/26 and H37Rv strains. The cytokine response in the lungs of C57BL/6 mice after infection with the 267/47, 120/26, and H37Rv strains was different. Notably, proinflammatory cytokine genes Il-1α, Il-6, Il-7, and Il-17, as well as anti-inflammatory genes Il-6 and Il-13, were downregulated after an infection caused by the 267/47 strain compared to those after infection with the H37Rv strain.

In response to the urgent unmet needs of heterogeneity, unpredictability, and diagnostic delay in systemic lupus erythematosus (SLE), we aimed to identify and validate new immunoglobulin (Ig)G and IgA autoantibody specificities. Using a KoRectly EXpressed technology-based microarrays (i-Ome Discovery; Sengenics), we screened for circulating IgG and IgA autoantibodies against 1609 proteins in 2 independent cohorts (discovery: NTC02890121; validation: NCT02890134) comprising patients with SLE (n = 199 and n = 30), primary Sjögren's disease (n = 115 and n = 31), and systemic sclerosis (n = 115 and n = 24), and healthy controls (HCs; n = 111 and n = 84), respectively. We identified and validated 5 IgG (anti-Lin-28 homolog A [LIN28A], anti-HNRNPA2B1, anti-HMG20B, anti-HMGB2, and anti-alpha-globin transcription factor CP2 [TFCP2]) and 4 IgA (anti-LIN28A, anti-HMG20B, anti-SUB1, and anti-TFCP2) autoantibodies that demonstrated high specificity for SLE (0.91-0.94), along with consistent and robust positivity (0.22-0.69) in differentially abundant autoantibody (daAAb) analysis between SLE and comparator groups. IgG and IgA anti-LIN28A levels varied over a 14-month follow-up in the validation cohort of newly diagnosed patients with SLE and exhibited metrics that outperformed those of traditional autoantibody markers such as anti-double-stranded DNA. Clustering of patients with SLE based on autoantibody positivity (levels above the HC median plus 2 IQRs in the discovery cohort) status revealed 1 subgroup demonstrating seroreactivity against multiple antigens, 3 exhibiting varying reactivity, and 1 showing no reactivity. In pathway analysis, daAAb targets pointed to DNA-binding and RNA-binding and transcription functions. Novel autoantibodies validated in this study may enhance diagnostics and molecular characterisation in SLE. The prominent IgA seroreactivity implicates important roles of mucosal tissues in SLE autoimmunity, warranting further investigation.