An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the “early” and “late” stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO.

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient’s risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05).

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of the HEV. The anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, the circulation of the same viral strain for five years was documented. All the human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. The sequences are from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size that was predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) that was predicted using birth–death skyline analysis has fluctuated around 1 over the past 20 years in Russia but is 10 times higher in Belgorod Region. In conclusion, the HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

The development of new and effective antibacterials for pharmaceutical or cosmetic skin care that have a low potential for the emergence and expansion of bacterial resistance is of high demand in scientific and applied research. Great hopes are placed on alternative agents such as bactericidal peptidoglycan hydrolases, depolymerases, etc. Enzybiotic-based preparations are being studied for the treatment of various infections and, among others, can be used as topical formulations and dressings with protein-polysaccharide complexes. Here, we investigate the antibiofilm properties of a novel enzybiotic cocktail of phage endolysin LysSi3 and bacteriocin lysostaphin, formulated in the alginate gel matrix and its ability to control the opportunistic skin-colonizing bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as mixed-species biofilms. Our results propose that the application of SiL-gel affects different components of biofilm extracellular polymeric substances, disrupts the matrix, and eliminates the bacteria embedded in it. This composition is highly effective against biofilms composed of Gram-negative and Gram-positive species and does not possess significant cytotoxic effects. Our data form the basis for the development of antibacterial skin care products with a gentle but effective mode of action.

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018–2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018–2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.