The combination of etiotropic antiviral drugs with Kagocel enhances the efficiency of antiviral therapy. Monitoring of antiviral cytokines during the treatment of influenza A is a convenient tool to verify the efficiency of antiviral therapy and needs to be more widely introduced into medical practice.

Background. The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases.The aim. To show the features of identifying the markers of Borrelia burgdorferi, tickborne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies.Methods. In 2019–2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies.Results. Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme- IgG antibodies appeared against the background of a reduced general condition. At the same time, high-avid IgG (cut-off index (COI) – 7.8) and IgM (COI = 1.2) antibodies to the TBE virus were detected. In July 2020, the patient was infected with SARSCoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequent blood samples (No. 4, 5, 6) we found TBEV antigen (optical density (OD) – 4.3; 1.9 and 2.0 respectively) and IgM (COI = 1.3; 0,9 and 0 respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %; 100 % and 63 % respectively). IgM antibodies to SARSCoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2; 8.1; 8.4 and 14.7 respectively).Conclusions. Therefore, using not only the common methods of diagnosing (PCR and ELISA), but also the determination of the antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease.

Резюме Цель. Установить степень повреждения ДНК лимфоцитов и определить уровень содержания 8-гидрокси-2дезоксигуанозина (8-OHdG) и 8-нитрогуанина (8-NO2G), общей антиоксидантной активности (ОАА) в сыворотке крови больных хроническими вирусными гепатитами С (ХВГС), В (ХВГВ). Материалы и методы. В исследовании приняли учас тие 100 человек с ХВГС, 50 с ХВГВ и 43 добровольца. Повреждения ДНК оценивали методом ДНК-комет. Уровень 8-NO2G и 8-OHdG определяли в образцах сыворотки крови с помощью наборов для ИФА. ОАА определяли по стандартной методике с ABTS. Статистическую обработку проводили с использованием пакета STATISTICA 10.0. Результаты. Отмечалась тенденция к увеличению уровня повреждений ДНК с прогрессированием стадии фиброза печени при ХВГВ и ХВГС. Обнаружены значимые отличия от показателя нормы 8-NO2G в группах F1, F2, F3 при ХВГС и в группах F2, F3, F4 (ρ<0,05) при ХВГВ. Во вех группах при ХВГС и в F2 и F4 при ХВГВ уровень 8-OHdG выше по сравнению с образцами контрольной группы (ρ=0,0001). Показаны корреляции между стадией фиброза печени и уровнем 8-NO2G и 8-OHdG соответственно (r=0,786620 и r=0,625844; ρ<0,05) при ХВГС и ХВГВ (r=0,573933 и r=0,478849; ρ<0,05). При исследовании ОАА у пациентов отмечалась тенденция к её истощению с развитием фибротических изменений, однако достоверные различия в сравнении с контролем были только на стадии фиброза F3 и F4 при ХВГС и F2, F4 (ρ<0,05) при ХВГВ. Заключение. Выявлен генотоксический эффект влияния вирусов гепатита В и С на ДНК лимфоцитов. Отмечено увеличение степени фрагментации ДНК с прогрессированием фиброза печени. Выявлена корреляция между стадией фиброза и биохимическими маркерами повреждения ДНК, а также показано декомпенсаторное снижение ОАА сыворотки на продвинутых стадиях фиброза печени.

The coexistence of various pathogens inside the patient’s body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.

The present study focuses on the comparative assessment of the therapeutic efficacy of the antiviral drugs riamilovir and umifenovir in the treatment of patients diagnosed with influenza. The aim of the study was to compare the clinical efficacy and safety, as well as the incidence of complications, of the use of antiviral drugs riamilovir and umifenovir and the use of only symptomatic therapy in patients with a confirmed diagnosis of influenza. All patients were hospitalized at the Regional Clinical Hospital No. 2 in Vladivostok. The study included 150 patients, who were divided into 3 groups (50 patients in each group), comparable in gender, age, and admission to the hospital. Patients of the first group received riamilovir, the second group received uminofenovir, patients of the third group received only symptomatic therapy (control group). The duration of clinical manifestations of the disease, hematological disorders, as well as the content of cytokines TNF-α and IL-10 in blood serum were assessed. The incidence of complications in each group was taken into account. As a result of the study, it was found that the inclusion of the antiviral drugs riamilovir and umifenovir in the therapy of influenza decreases the amount of the pro-inflammatory cytokine TNF-α after 5 days of treatment; and in case of symptomatic therapy its level significantly exceeded the reference values. The level of anti-inflammatory cytokine IL-10 on the 5th day of treatment in the main group was three times lower than in the control group. Thus, riamilovir and umifenovir effectively relieve the main symptoms of the disease, reduce the incidence of complications, and reduce the severity of the inflammatory response by the 5th day of treatment.