Vol 10, No 2 (2020)

The COVID-19 epidemic curve in China can be divided into several stages. Despite transparency in informing the world public about clusters of undiagnosed viral pneumonia, the country’s health care at the first stage of the epidemic was not ready to provide adequate and rapid response for a fast increase in the number of patients with COVID-19, infection control measures were not fully implemented, which also led to a large number of nosocomial cases of infection among medical workers and patients. Socially vulnerable groups of the population did not refer for medical assistance in a timely manner due to the lack of the disease danger understanding and also in connection with the high cost for them of medical aid. At the second stage, simultaneously with the restrictive measures introduced by the government, the entire health care system was rebooted: free medical care for patients with COVID-19 was provided and the strictest infection control measures were implemented, multi-level contact tracking system using IT technologies was organized, and the capacity of hospitals was increased many times. Through the joint efforts of ministries, mass media, social networks and volunteer movements, an unprecedented social mobilization of the population was achieved. Strict implementation of the entire set of measures aimed at fighting the epidemic allowed to take it under strict control at the third stage and practically eliminate the epidemic after 2,5 months. China’s response to the COVID-19 epidemic can be useful to other countries, in fighting the current pandemic and in preparing for a response to biological threats in the future.

Coronavirus infection 2019 is considered a modern challenge to the world community. In the absence of vaccines and antivirals, effective and safe medicines are an urgent request from the healthcare system. We have evaluated the medical technologies for COVID-19 which are being examined. The search was conducted on the СlinicalTrials.gov at the beginning of April 2020. As a result it was shown that the growth of new clinical trials in the world devoted to COVID-19 is growing by 65% per week. More often, interventional clinical trials of the II and III phases are carried out. Most studies are planned or conducted in Western Europe (n = 92), China (n = 79), and the United States (n = 51). Surrogate points are usually evaluated, such as: clinical recovery, symptom-based disease relief (fever, cough, diarrhea, myalgia, shortness of breath), lack of progression of shortness of breath, rate of artificial ventilation, rate of admission to the intensive care unit, etc. It is antimalarial drugs that are mainly studied. Currently, it is not possible to discuss the efficacy and safety of a drug in the treatment of COVID-19, as most studies have just begun. The therapeutic regimens proposed now in clinical recommendations have no evidence base, and the studies indicated in them are at best considered hypothesizing.

Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45⁺/CD19⁺ B lymphocytes and natural killer cells (CD16/32⁺/CD3^–). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32⁺/CD3^– expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4⁺/CD25⁺/Fox P3 regulatory T cells, CD4⁺ T helpers and CD8⁺ cytotoxic cells, except for a sharply decreased count of activated CD4⁺/CD25⁺ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines.

Currently, a rise in incidence of polyethological inflammation of the upper respiratory tract mucosa paralleled by altered resident and transient microbiota displaying in many cases increased antibiotic resistance has been noted. Opportunistic microbes play a major role in developing inflammatory process in Pirogov–Waldeyer’s ring. An inflammatory process occurring in the tonsillar lymphatic tissue results in host systemic complications. Fighting against acute and chronic infections of the upper respiratory tract holds the main task in pediatric otorhinolaryngology, as they can consequently elicit the cardiovascular, genitourinary and musculoskeletal complications. The results of studies examining this issue remain very contradictory, which accounted for a need to conduct our study on the territory of Moldova featured with mixed climatic conditions. Here, we wanted to study a role of microbial factor in etiopathogenesis of chronic tonsillitis in children. Bacteriological microbiota data for superficial palatine tonsils were obtained form 608 children subdivided into 5 groups: group I — 333 children with compensated chronic tonsillitis; group II — 87 children with decompensated chronic tonsillitis; group III — 91 children with acute upper respiratory tract infections (comparison group); group IV — 48 children with acute upper respiratory tract infections treated with antibiotic therapy; group V — 49 apparently healthy children (control group). It was found that β-hemolytic streptococcus exerting high sensitivity to virtually all antibiotics groups was detected in 17.4% of children with acute tonsilar inflammatory processes and decompensated defense in the lymphatic pharyngeal ring compared to 3.5% in control group. Streptococcus pneumoniae was isolated in all study groups ranging within 4.8–21.7%, including 14% in apparently healthy children characterized by reduced antibiotics sensitivity. The data obtained suggest that sickly children with acute and chronic upper respiratory tract infections constitute a risk group for developing somatic diseases. The high incidence of Streptococcus pneumoniae indicates a need for performing immunoprophylaxis, use of therapeutic vaccination as a up-to-date, combined approach in treatment of such pediatric cohort.

It is known that children with congenital cleft lip and palate are suffering from recurrent respiratory infections, which worsen the state of their health, and also complicate the results of reconstructive surgical treatment. The aim of the study was to detect defects of mucosal immunity in children with congenital cleft lip and palate, suffering from recurrent respiratory infections, and to create the program of local interferon corrective therapy with an assessment of its effectiveness. The studies included 56 children from the age of 1 to 3 years. Three groups of children were formed: group 1 – 26 children with congenital cleft lip and palate (antibiotic therapy); group 2 — 30 children with congenital cleft lip and palate (antibiotic therapy + local interferon therapy), group 3 — the control group. The clinical examination included a medical history, an assessment of the symptoms of recurrent episodes of acute respiratory infections and exacerbations of chronic infections. Microbiological studies were performed using standard methods. The status of local immunity was detected: the concentrations of secretory IgA, cytokines IL-17, IL-4, IL-6, IL-1β, IFNγ in the oral fluid were tested by ELISA. Results of the study established that in group 1 and group 2 clinical criteria of immunodeficiency with an infectious syndrome were revealed: repeated acute respiratory viral infections from 10 or more times a year, complicated by frequent exacerbations of chronic bacterial infection (up to 10 or more per year). Assessment of the state of local immunity in children with congenital cleft lip and palate revealed a lack of sIgA compared with the control group. Before treatment in group 2 oral fluid level of IL-17, IL-6 were statistically significant increase (p < 0.05); the results of the study also established increase in the level of IL-1β and a decrease in anti-inflammatory IL-4 and regulatory IFNγ relative to the control group (p > 0.05). After complex treatment with the inclusion of local interferon therapy in group 2 the appearance of sIgA, increase in the concentration of IL-4, IL-1β and a decrease IL-17 in oral fluid were observed (p > 0.05). The concentrations of IL-6, IFNγ did not change (p > 0.05). After treatment in group 2 there were a decrease in exacerbations of chronic upper respiratory tract infection and in frequency of acute respiratory viral infections compared with group 1 (p < 0.05). Positive clinical efficacy of local interferon therapy (the gel of recombinant IFNα2b in combination with oxidants — Viferon gel) in the process of staged rehabilitation of children with congenital cleft lip and palate has a protective clinical effect in reducing the frequency of acute respiratory viral infections, reducing the number of postoperative complications, reducing hospital stay, duration of antibacterial therapy and the number of exacerbations of chronic bacterial infection.

A high measles incidence rate has been registered in Russia in recent years, with adults being actively involved in the epidemic process (about 40% of patients), thereby underlying relevance of assessing herd immunity in different  age groups to measure its risk. The data on examining serum antibodies to measles virus in 402 residents of Petrozavodsk are shown: 164 and 238 subjects were born in 1948–1968 (51–71 years) and 1970–1983 (36–50 years), respectively. It was found that the second group had significantly higher percentage not only of seropositive persons (94.1±1.5 vs. 77.4±3.3%, respectively), but also frequency of detected high IgG level (5 and more IU/l) reaching 39.7±3.5 vs. 15.4±5.8%, respectively. Analysis of vaccination history showed that of 351 people with protective antibody levels, 20.9% were vaccinated once or twice, 14 of them in childhood and 63 within the 15 years prior to the study. Of the 51 people with no measles antibodies or below protective level, 13.7% were vaccinated: five in childhood, and two within the last 15 years. Among those who was born in 1948–1968, 87.1±2.2% provided no information about previous vaccinations and probably were not vaccinated. In this group, percentage of those examined with a protective antibody level was significantly higher than in the 36–50 years group — 87.1±2.2 and 62.2±4.3%, respectively. In addition, 23 subjects confirmed that they recovered after measles in childhood. Of these, antibodies were detected in 21 subjects, including 9 having serum titer at level of 5 or more IU/ml. Until 1969, the Republic of Karelia registered a high level of measles morbidity (477–2176,0 per 100 thousand). The predominance in the group born before 1969, individuals seropositive to measles mainly at high titer, indicates that intense post-infectious immunity was preserved. The lack of protective level of antibodies to measles virus in 22.6% of persons aged 36–50 years (1969–1983 year of birth), due to the low level of post-infectious and insufficient durability of post-vaccination immunity allowing to definer them as a high risk group for measles infection.

Until now, it has been considered that infectivity of the varicella-zoster virus (VZV) is closely related to target cell, and newly formed virus is not released into the culture medium. It is also known that it is hard to grow VZV in cell cultures, due to its slow replication rate and a limited range of sensitive cell cultures. In addition, VZV isolation depends on type of cell culture used, nature of clinical material, presence of viable virus and transport time. Objectives. To study production of infectious extracellular VZV in various cell cultures. Materials and methods. Eight cell cultures were used, including human embryonic diploid lung cells and human embryonic dermomuscular tissue (KM-27), as well as continuous human and monkey cell lines. Crusts detached from vesicular lesions were used as clinical isolates, which were placed into cryo-vials added with transport medium and transferred in liquid nitrogen. VZV infectivity was assessed in cell cultures by using hemo-adsorption assay with erythrocyte suspension isolated from guinea pig or human zero group blood and confirmed by indirect immunofluorescence with polyclonal sera from varicella or herpes zoster convalescents. Results. There were examined 27 clinical samples consisting of crusts from vesicular lesions isolated from patients with chickenpox, as well as one sample from 63-year old patient with exacerbated recurrent herpes zoster. Primary infection with clinical isolates was performed on diploid human lung embryo cells (HLEC) at low temperature. It was found that clinical samples collected within day 1–18 inclusive after the onset of skin eruption were able to induce cytopathic effects in HLEC cell monolayer such as cytolysis around dermal crusts. Specificity of cytopathic effect was confirmed by using real-time polymerase chain reaction (RT-PCR). Viral antigens were prepared on 7 cell lines infected with the laboratory strain Ellen VZV (USA) to assess the immune sera. A high anti-VZV specificity of mouse sera was detected by ELISA while all the lysates of infected cell lines were used as the solid-phase sorbent. In experiments on VZV reproduction demonstrated that extracellular virus was released into the culture medium starting from day 1 after infection of target cells, and infectivity of the virus-containing fluid ascends during further cultivation.