Novel prognostic determinants of COVID-19-related mortality: A pilot study on severely-ill patients in Russia.

COVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification. Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment.

The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes.

The aim of this study was to identify single nucleotide variants in genes associated with susceptibility to or severe outcomes of COVID-19. A total of 319 genomic DNA samples from patients with varying degrees of disease severity and 78 control DNA samples from people who had regular or prolonged contact with patients with COVID-19 but did not have clinical manifestations and/or antibodies to SARS-CoV-2. Seven SNPs were identified that were statistically associated with disease risk or severe course, rs1799864 in the CCR2 gene (OR = 2.21), rs1990760 in the IFIH1 gene (OR = 2.41), rs1800629 in the TNF gene (OR = 1.98), rs75603675 in the TMPRSS2 gene (OR = 1.86), rs7842 in the C3AR1 gene (OR = 2.08), rs179008 in the gene TLR7 (OR = 1.85), rs324011 in the C3AR1 gene (OR = 2.08), rs179008 in the TLR7 gene (OR = 1.85), and rs324011 in the STAT6 gene (OR = 1.84), as well as two variants associated with protection from COVID-19, rs744166 in the STAT3 gene (OR = 0.36) and rs1898830 in the TLR2 gene (OR = 0.47). The genotype in the region of these markers can be the criterion of the therapeutic approach for patients with COVID-19.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: COVID-19 convalescent plasma is an experimental treatment against SARS-CoV-2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS-CoV2 in convalescent plasma. MATERIALS AND METHODS: A total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N-proteins of SARS-CoV-2 were measured before and after pathogen reduction. RESULTS: The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7%, respectively) had a one-step (two-step, respectively) decrease. Paired two-sample comparisons (M vs. A, M vs. R and A vs. R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment. CONCLUSION: Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

The Preparation of Convencent Plasma and Recruiting of Donors during the COVID-19 Pandemic

Background. The pandemic of the new coronavirus infection has challenged the medical community for quickly finding and implementing effective methods of treatment. In the absence of a vaccine or specific therapy with proven effectiveness, the usage of convalescent plasma can be the one of perspective methods. An important aspect of this technology is the efficient and safe preparation of convalescent plasma. To date, in the world literature there are practically no publications about donor recruitment and the specifics of the preparation of convalescent plasma. Purpose of the research. Presentation of the experience of organizing a workflow for recruiting donors and stockpiling of convalescent plasma with a high titer of virus-neutralizing antibodies to SARS-CoV-2. Methods. The analysis of the work of the Blood Service of the Moscow Department of Health for stockpiling of COVID-19 convalescent plasma has been executed. In total it has been stockpiled 1240 doses. The normative documentation has been developed by a working group on the basis of the current federal legislation of Russian federation and been approved by the Moscow Department of Health. The titer of neutralizing antibodies (VNA) has been determined as the basic method for assessing the immunological viability of convalescent plasma. The main characteristics of donors, the characteristics of the disease course, the results of preliminary testing for the presence of specific antibodies by ELISA and CLIA methods has been compared with VNA titers in the stockpiled convalescent plasma. Results. Due to a Moscow Health Department’s order No. 325 dated 01.04.2020 (a basic local regulatory document) it has been developed a regulation for the stockpiling, examination, storage, safety and transfering of fresh frozen pathogen-reduced plasma of COVID-19 convalescent donors to medical organizations of the Moscow Health Department. For arranging an interaction with donors it has been created a call-center. For effective preliminary selection, it has been formed a donor characteristics list, which has been combined with screening of specific antibodies by ELISA and CLIA methods. Conclusions. Developed a system of recruiting donors and procurement process of convalescent plasma for treatment СOVID-19, which includes the necessary regulations, algorithms for the selection and recruitment of donors, the registry of donors and recipients, algorithms, efficiency and safety of convalescent plasma. Обоснование. Пандемия новой коронавирусной инфекции поставила перед медицинским сообществом задачу быстрого поиска и внедрения эффективных методик лечения. В условиях отсутствия вакцины и средств специфической терапии с доказанной эффективностью в качестве одной из перспективных методик рассматривается трансфузия реконвалесцентной плазмы (РП). Важным аспектом данной технологии является заготовка эффективного и безопасного компонента. На сегодняшний день публикации по рекрутингу доноров и особенностях заготовки РП в мировой литературе практически отсутствуют. Цель исследования - Анализ опыта организации рабочего процесса по привлечению доноров и заготовке РП с высоким титром вируснейтрализующих антител к SARS-CoV-2. Методы. Проведен анализ работы Службы крови Департамента здравоохранения г. Москвы (ДЗМ) по заготовке РП COVID-19. Всего заготовлено 1240 доз. Нормативная документация разработана рабочей группой на основании действующего федерального законодательства и утверждена ДЗМ. Как базовая методика оценки иммунологической состоятельности РП, определен титр вируснейтрализующих антител (ВНА). Проведено сопоставление основных характеристик доноров, особенностей течения заболевания, результатов предварительного тестирования на наличие специфических антител методами ИФА и ИХЛА с титрами ВНА заготовленной РП. Результаты. Работа по заготовке, обследованию, хранению, обеспечению безопасности и передаче в медицинские организации ДМЗ свежезамороженной патогенредуцированной плазмы доноров-реконвалесцентов COVID-19 была организована на основании приказа ДЗМ от 01.04.2020 № 325 как базового локального нормативного документа. Для оптимальной коммуникации с состоявшимися донорами и привлечения реконвалесцентов использовались ресурсы колл-центра. Для эффективного предварительного отбора доноров применялись анализ характеристик донора (плазма с наибольшими значениями титра ВНА ожидаема от доноров-мужчин, переболевших с признаками явной вирусной пневмонии) и результаты скрининга специфических антител методами ИФА и ИХЛА. Заключение. Разработана система обеспечения рекрутинга доноров и процесса заготовки РП для лечения СOVID-19, включающая необходимые нормативные документы, алгоритмы отбора и привлечения доноров, реестр доноров и реципиентов, алгоритмы обеспечения эффективности и безопасности РП.

Thermal Helium-Oxygen Mixture as Part of a Treatment Protocol for Patients with COVID-19

Background. The paper discusses the use of a thermal helium-oxygen mixture (t-Не/О2 ), a novel technology, in treating patients with the 2019-nCoV acute respiratory disease (COVID-19) who develop life-threatening respiratory failure. Aim - to evaluate the safety and efficacy of t-Не/О2 inhalation combined with standard therapy in the treatment of acute respiratory failure in patients with COVID-19. Materials and Methods. This was a single-center, randomized, prospective study of 70 patients with COVID-19. All patients were divided into two groups: in Group 1 (n = 38) patients received t-He/О2 in addition to the standard COVID-19 treatment;and in Group 2 (n = 32) patients were given the standard treatment in accordance with the Clinical Treatment Guidelines for patients with COVID-19, developed by the Ministry of Health of the Russian Federation. The male/female ratio was 18/20 in Group 1 and 18/14 in Group 2. The mean age of the patients in the study was 53.5 years (43;62): 56 years (42;64) in Group 1 and 52 years (43;66) in Group 2. All patients had computed tomography (CT) signs of lung injury: ground-glass opacities and areas of consolidation. SARS-CoV-2 RNA was detected in 30 Group 1 patients and 28 Group 2 patients. The patients were matched by sex, age, body mass index (BMI), area of pulmonary involvement, and laboratory findings. All patients provided voluntary informed consent to participate in the study and signed a consent form. Results. Inhalation of thermal helium-oxygen mixture combined with standard therapy did not cause any procedure-related side effects in any of the patients. The following changes were observed in all patients: pO2 /FiO2 , SpO2 , and lymphocyte counts increased, C-reactive protein (CRP) levels decreased, and D-dimer and ferritin levels returned to normal. In Group 1 statistically significant changes in the above-mentioned parameters were seen within three days, while in Group 2 the same changes were observed between Days 7 and 10 of treatment. In Group 1 patients cleared SARS-CoV-2 within 48-72 hours after initiation of inhalation, which was confirmed by polymerase chain reaction (PCR), and in Group 2 virus elimination was achieved within 72-168 hours. Conclusion. The addition of inhalation of a thermal gas mixture of helium and oxygen (t-He/О2 ) to the standard therapy for patients with SARS-CoV-2 infection, CT signs of pneumonia (grades СT2 or CT3), and acute respiratory failure improves gas exchange, contributes to a more rapid virus elimination, and indirectly reduces inflammation. Обоснование. В представленной работе речь пойдет о новой технологии применения термического гелия и кислорода (t-Не/О2 ) в лечении больных с вирусным заболеванием СOVID-19 на этапе развития жизнеугрожающего синдрома дыхательной недостаточности. Цель - изучить безопасность и эффективность ингаляционной терапии t-Не/О2 в лечении острой дыхательной недостаточности пациентов с СOVID-19 на фоне стандартной терапии. Материалы и методы. В одноцентровое рандомизированное проспективное исследование было включено 70 пациентов с COVID-19. Пациенты были разделены на две группы: в первой (n = 38) в стандартный протокол лечения COVID-19 была включена терапия t-Не/О2 ;во второй (n = 32) проводилась стандартная терапия в соответствии с клиническими рекомендациями Минздрава России для больных с COVID. В первой группе соотношение мужчины/женщины - 18/20, а во второй - 18/14. Средний возраст пациентов в исследовании составлял 53,5 года (43 года - мужчины;62 года - женщины), в первой группе - 56 лет (42 и 64 года соответственно), во второй - 52 года (43 и 66 лет). У всех пациентов имелись КТ-признаки поражения легких по типу «матового стекла», участки консолидации. Тест РНК коронавируса SARS-CoV-2 положительный в первой группе у 30 пациентов, во второй - у 28. Пациенты сопоставимы по полу, возрасту, индексу массы тела (ИМТ), площади поражения легочной паренхимы, лабораторным данным. Всеми пациентами было подписано информированное добровольное согласие на участие в исследовании. Результаты. Вследствие применения термической гелий-кислородной смеси на фоне стандартной терапии ни у одного пациента объективных побочных эффектов, связанных с процедурой, не выявлено. У всех пациентов обнаружены следующие изменения: повышение pО2 /FiO2, SpO2 и уровня лимфоцитов, снижение концентрации С-реактивного белка, восстановление уровней Д-димера, ферритина. Эти признаки статистически значимо изменились в первой группе в течение 3 сут, тогда как во второй группе - на 7-10-е сут терапии. Элиминация вируса SARS-CoV-2 в первой группе происходила в течение 48-72 ч от момента начала ингаляции, что подтверждалось методом ПЦР, а во второй - в течение 72-168 ч. Заключение. Включение ингаляций термической газовой смеси гелия с кислородом (t-Не/О2 ) в стандартную терапию пациентов, переносящих инфекционное заболевание, вызванное SARS-CоV-2, c КТ-признаками пневмонии (КТ2, КТ3), с острой дыхательной недостаточностью улучшает газообмен, способствует ускорению элиминации вируса и опосредованно повышает противовоспалительный эффект.

Professional burnout, symptoms of emotional distress and distress among healthcare professionals during the COVID-19 epidemic

The article presents the results of a synthesis by Australian and Canadian scientists (Kisely et al, 2020) of 59 reliable studies of the effects of work during various epidemics, including COVID-19, on mental health and well-being of medical workers in different countries. The research includes the level of professional burnout, symptoms of emotional ill-being, and distress data based on the analysis of a data sample from 248 involved healthcare professionals of Russian medical institutions. They anonymously and voluntarily filled up the Google-form that contained a methodical complex during the COVID-19 epidemic. The complex included: A.Beck Depression Scale, A. Beck Anxiety Scale, J. Goland Distress Rating Scale, K. Maslach Professional Burnout Inventory. The research showed that during the epidemic, most healthcare professionals experienced evidence of the professional burnout (60% complain of emotional exhaustion), moderate and severe indicators of depression (23%), moderate and severe anxiety indicators (25%). Also, a suicidal trend was found (10%). Negative emotions (fear of infection, loneliness and isolation sense), organizational problems (personal protective equipment deficit), physical discomfort (inconvenience of protective clothing, lack of sleep), and communicative difficulties have a great influence on the emotional distress of healthcare professionals. Information "noise" and personal protective equipment deficit often performs as a problem area. Healthcare professionals involved in supporting COVID-19 patients have higher rates of professional burnout, depression, and anxiety. At the same time, high professional responsibility and motivation are maintained by the majority of specialists providing care to patients with COVID-19. Region healthcare professionals differ from Moscow healthcare professionals by higher rates of depression and anxiety and frequently complain about personal protective equipment deficit, leadership mistrust, or disagreement with them. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Thermovaccination - thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection.

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.