Cytokine Storm Signature in Patients with Moderate and Severe COVID-19.

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1ß, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19.

Genotype imputation and polygenic score estimation in northwestern Russian population.

Numerous studies demonstrated the lack of transferability of polygenic score (PGS) models across populations and the problem arising from unequal presentation of ancestries across genetic studies. However, even within European ancestry there are ethnic groups that are rarely presented in genetic studies. For instance, Russians, being one of the largest, diverse, and yet understudied group in Europe. In this study, we evaluated the reliability of genotype imputation for the Russian cohort by testing several commonly used imputation reference panels (e.g. HRC, 1000G, HGDP). HRC, in comparison with two other panels, showed the most accurate results based on both imputation accuracy and allele frequency concordance between masked and imputed genotypes. We built polygenic score models based on GWAS results from the UK biobank, measured the explained phenotypic variance in the Russian cohort attributed to polygenic scores for 11 phenotypes, collected in the clinic for each participant, and finally explored the role of allele frequency discordance between the UK biobank and the study cohort in the resulting PGS performance.

Case Report: Supernormal Vascular Aging in Leningrad Siege Survivors.

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.

The Significance of Phenotyping and Quantification of Plasma Extracellular Vesicles Levels Using High-Sensitivity Flow Cytometry during COVID-19 Treatment.

New investigation results point to the potential participation of extracellular vesicles (EVs) in the pathogenesis of coronavirus infection, its progression, and mechanisms of the therapy effectiveness. This dictates the necessity to transfer scientific testing technologies to medical practice. Here, we demonstrated the method of phenotyping and quantitative analysis of plasma EVs based on differential centrifugation, immunostaining, and high-sensitivity multicolor flow cytometry. We used EV markers that were potentially associated with SARS-CoV-2 dissemination via vesicles and cell-origination markers, characterizing objects from different cell types that could influence clinical manifestation of COVID-19. Plasma levels of CD235a+ and CD14+ EVs in patients with moderate infection were significantly increased while CD8+ and CD19+ EVs were decreased comparing with HD. Patients with severe infection had lower levels of CD4+, CD19+, and CD146+ EVs than HD. These findings demonstrate that EV concentrations in COVID-19 are severity related. Moreover, the three-point dynamic assessment demonstrated significant loss of CD63+ and CD147+ plasma EVs. The used method can be a convenient tool for vital infection pathogenesis investigation and for COVID-19 diagnostics.

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19.

BACKGROUND: The immunological changes associated with COVID-19 are largely unknown. METHODS: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry. RESULTS: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L- (CM) and CD45RA-CD62L- (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells "classical" Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38- and IgD-CD38- were decreased. The frequency of IgD+CD27+ and IgD-CD27+ B cells was significantly reduced in severe COVID-19 cases. CONCLUSIONS: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

Plants with genetically encoded autoluminescence.

Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants.

Author Correction: Plants with genetically encoded autoluminescence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.