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Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical and histopathological features of fatal HFRS in the Udmurt Republic (Udmurtia), located in the European part of Russia. This retrospective observational study included all fatal cases of HFRS that occurred in Udmurtia from January 2010 through December 2019. The most relevant clinical and autopsy data of these cases were recorded through a review of the patients' medical records and autopsy reports. During 2010-2019, Udmurtia had 41 fatal cases of HFRS of a total of 10,312 confirmed cases (case-fatality rate of 0.4%). Twenty-seven patients died in hypotensive and oliguric phases of HFRS due to refractory septic shock and acute respiratory distress syndrome. Fourteen patients died in the polyuric phase of the disease from complications of acute kidney injury or because of hospital-acquired bacterial infections. Multiorgan involvement was noted in all autopsies with variable degrees of generalized venous congestion, interstitial edema, capillary wall thickening, perivascular deposition of plasma proteins, microthrombosis formation, and perivascular hemorrhage. The more prominent histopathological features were seen in kidneys, lungs, and hypophysis.

An analysis of coronavirus infection in Russia and evaluation of different AVT regimens effectiveness.The study involved a retrospective analysis of 1082 patient records with laboratory-confirmed COVID-19 in 17 regions of Russia. The number of men and women was equal, mean age 48.718.1 (median 50). Patients with moderate COVID-19 (85%) versus mild COVID-19 (15%) were characterized by higher age (median 54 vs 21 years; p0.001), higher body mass index (27.8 vs 23.4; p0.001), prevalence of chronic diseases (75.3% vs 8.5%; p0.001), including circulatory system diseases (37.8%). Moderate COVID-19 characterized higher intoxication (10.86.1 vs 4.22.7 days; p0.001) and catarrhal symptoms duration (10.25.4 vs 6.14.1 days; p0.001).During hospitalization 92% of the patients received AVT, 77% antibiotics, and 16% corticosteroids. Umifenovir therapy resulted in a significant reduction of intoxication (8.75.5 vs 11.75.5 days; p0.001) and catarrhal symptoms duration (8.85.1 vs 12.04.9 days; p0.001) compared to the group without AVT. The usage of INF reduced intoxication symptoms compared with the group without AVT (8.97.5 vs 11.75.5; p0.05). Therapy with hydroxychloroquine, imidazolylethanamide pentandioic acid, and lopinavir + ritonavir combination did not affect the course of COVID-19. Most of adverse reactions were related to antibiotics.Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients.Обоснование. В течение 2020 г. в Российской Федерации был рекомендован к применению ряд этиотропных препаратов, однако вопрос противовирусной терапии (ПВТ) COVID-19 остается открытым. Цель. Фармакоэпидемиологический анализ коронавирусной инфекции COVID-19 на территории РФ с февраля по ноябрь 2020 г. и оценка эффективности разных схем ПВТ. Материалы и методы. Анализируемая популяция включала 1082 пациента с лабораторно подтвержденным диагнозом COVID-19, проходивших стационарное лечение в лечебных учреждениях в 17 регионах РФ. Средний возраст составил 48,718,1 года (медиана возраста 50 лет), равное число мужчин и женщин. Среднетяжелая форма COVID-19 (85% пациентов) по сравнению с легкой (15%) характеризовалась большим возрастом пациентов (медиана возраста 54 vs 21 год; p0,001), индексом массы тела (27,8 vs 23,4; p0,001), частотой хронических заболеваний в анамнезе (75,3% vs 8,5%; p0,001), в основном заболевания системы кровообращения (37,8%). Клиническая картина среднетяжелой формы COVID-19 отличалась более длительной продолжительностью симптомов интоксикации (10,86,1 vs 4,22,7 дня; p0,001), катаральных симптомов (10,25,4 vs 6,14,1 дня; p0,001). Результаты. Во время лечения в стационаре 92% пациентов получали ПВТ, 77% антибактериальные препараты, 16% кортикостероиды (дексаметазон). Терапия умифеновиром приводила к значимому снижению продолжительности интоксикационного (8,75,5 vs 11,75,5 дня; p0,001) и катарального (8,85,1 vs 12,04,9 дня; p0,001) синдромов в сравнении с группой без ПВТ. Применение интерферона снижало продолжительность симптомов интоксикации в сравнении с группой без ПВТ (8,97,5 vs 11,75,5 дня; p0,05). Терапия гидроксихлорохином, имидазолилэтанамид пентандиовой кислотой и комбинацией лопинавир + ритонавир не влияла на течение COVID-19. Нежелательные реакции в основном были связаны с приемом антибиотиков. Заключение. Умифеновир снижал продолжительность интоксикационных и катаральных симптомов. Включение интерферона в схемы ПВТ также приводит к улучшению клинической картины.

Intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus in Asia. However, its therapeutic benefits for HFRS caused by Puumala virus (PUUV) in Europe are still unknown.A randomized, open-label study of efficacy and safety of intravenous ribavirin in the treatment of HFRS was conducted in the European part of Russia. Seventy-three patients with suspected HFRS within 4 d of the onset of the disease were randomized to receive either intravenous ribavirin (33 mg/kg, followed by 16 mg/kg given every 6 h for 4 d and by 8 mg/kg given every 8 h for 3 d) plus standard therapy (n = 37) or standard therapy alone (n = 36). The primary outcome was the average change from baseline in viral load over time estimated as area under the viral load curve minus baseline (AUCMB). Fifty-five patients with HFRS confirmed by nested reverse transcriptase - polymerase chain reaction (PCR) assay were included in the assessment of the efficacy. All patients entered into the clinical trial were included in the assessment of the safety.PUUV was detected in all cases of confirmed HFRS. Viral load kinetics were similar in both treatment groups. Significantly more patients receiving ribavirin than standard therapy experienced low haemoglobin level (95% vs 36%), hyperbilirubinemia (81% vs 3%), sinus bradycardia (43% vs 14%), and rash (19% vs 0%).Results of the study showed insufficient efficacy and safety of intravenous ribavirin in the treatment of HFRS caused by PUUV.