The COVID-19 pandemic has drawn the attention of many researchers to the interaction between pathogen and host genomes. Over the last two years, numerous studies have been conducted to identify the genetic risk factors that predict COVID-19 severity and outcome. However, such an analysis might be complicated in cohorts of limited size and/or in case of limited breadth of genome coverage. In this work, we tried to circumvent these challenges by searching for candidate genes and genetic variants associated with a variety of quantitative and binary traits in a cohort of 840 COVID-19 patients from Russia. While we found no gene- or pathway-level associations with the disease severity and outcome, we discovered eleven independent candidate loci associated with quantitative traits in COVID-19 patients. Out of these, the most significant associations correspond to rs1651553 in MYH14p = 1.4 × 10⁻⁷), rs11243705 in SETX (p = 8.2 × 10⁻⁶), and rs16885 in ATXN1 (p = 1.3 × 10⁻⁵). One of the identified variants, rs33985936 in SCN11A, was successfully replicated in an independent study, and three of the variants were found to be associated with blood-related quantitative traits according to the UK Biobank data (rs33985936 in SCN11A, rs16885 in ATXN1, and rs4747194 in CDH23). Moreover, we show that a risk score based on these variants can predict the severity and outcome of hospitalization in our cohort of patients. Given these findings, we believe that our work may serve as proof-of-concept study demonstrating the utility of quantitative traits and extensive phenotyping for identification of genetic risk factors of severe COVID-19.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The aim of this research was to identify erythrocyte morphology abnormalities that occur in COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800–2200 cells per donor) and 5 COVID-19 patients (800–1900 cells per patient) were examined using low-voltage scanning electron microscopy. We did not discover any forms of erythrocyte morphology abnormalities that would be specific to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p = 0.01) and a decrease in the number of spherocytes (p = 0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p = 0.004) and interquartile range (p = 0.009) when assessing erythrocyte size. The limitation of our study is a small number of participants.

TRNA-derived fragments function as markers in addition to playing the key role of signalling molecules in a number of disorders. It is known that the repertoire of these molecules differs greatly in different cell types and varies depending on the physiological condition. The aim of our research was to compare the pattern of tRF expression in the main blood cell types and to determine how the composition of these molecules changes during COVID-19-induced cytokine storms. Erythrocytes, monocytes, lymphocytes, neutrophils, basophils and eosinophils from control donors and patients with severe COVID-19 were obtained by fluorescence sorting. We extracted RNA from FACS-sorted cells and performed NGS of short RNAs. The composition of tRNA-derived fragments was analysed by applying a semi-custom bioinformatic pipeline. In this study, we assessed the length and type distribution of tRFs and reported the 150 most prevalent tRF sequences across all cell types. Additionally, we demonstrated a significant (p < 0.05, fold change >16) change in the pattern of tRFs in erythrocytes (21 downregulated, 12 upregulated), monocytes (53 downregulated, 38 upregulated) and lymphocytes (49 upregulated) in patients with severe COVID-19. Thus, different blood cell types exhibit a significant variety of tRFs and react to the cytokine storm by dramatically changing their differential expression patterns. We suppose that the observed phenomenon occurs due to the regulation of nucleotide modifications and alterations in activity of various Rnases.

Background: According to WHO, as of March 31, 2021, 127 877 462 confirmed cases of the new COVID-19 coronavirus infection were registered in the world, including 2 796 561 deaths (WHO Coronavirus Disease). COVID-19 is characterized by a wide range of clinical manifestations, from asymptomatic to a rapid progression to severe and extremely severe. Predictive biomarkers for the early detection of high-risk individuals have become a matter of great medical urgency. Aims: Search for the predictors of a cytokine storm in patients with COVID-19 infection and creation of a risk scale of this complication for practical applications. Methods: The study included 458 patients with confirmed COVID-19 infection with signs of viral lung lesions according to the computer tomography data. The patients were divided into 2 groups: those with a stable course of moderate severity (100 patients) and those with progressive moderate, severe and extremely severe course (358 patients). Results: It has been established that the main risk factors for the development of a cytokine storm in COVID-19 patients are the following: interleukin-6 concentration 23 pg/ ml, dynamics of the index on the NEWS scale 0, ferritin concentration 485 ng/ml, D-dimer concentration 2.1, C-reactive protein concentration 50 mg/l, number of lymphocytes in the blood 0.72109/l, age 40 years. The cytokine storm incidence correlates with an increase in the number of risk factors. For the practical testing the scale was applied in 3 groups. In patients of the first group (01 factor) almost no cytokine storm risk was found, in the second group (2 -3 factors) the probability of the storm was 55% (increase by 35.5 times), in the third group (4 risk factors) it reached 96% (increase by 718 times). Conclusion: The diagnostic and monitoring criteria of a cytokine storm have been established in patients with COVID-19 infection. The developed prognostic scale allows identification of patients at high risk of developing a cytokine storm so that early anti-inflammatory therapy could be started.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The purpose of this research was to identify erythrocyte types that were unique to COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800-2200 cells for each donor) and 5 COVID-19 patients (800-1900 cells for each patient) were examined using low voltage scanning electron microscopy. We did not discover any forms of poikilocytes that would be unique to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p=0.01) and a decrease in the number of spherocytes (p=0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p=0.004) and interquartile range (p=0.009) when assessing erythrocyte size.

Введение. Изучение патоморфогенеза и танатогенеза при новой коронавирусной инфекции стало в период 2020-2021 гг. новым профессиональным вызовом для патологоанатомической службы и во многом определило основное направление диагностической и научно-исследовательской деятельности в этот период.Цель: провести клинико-морфологических анализ летальных исходов и обобщить полученный опыт исследования тел пациентов, находившихся на стационарном лечении в первую волну пандемии и умерших от тяжелых форм новой коронавирусной инфекции.Материалы и методы. В исследование включены клинико-морфологические данные, полученные при изучении медицинской документации и тел 101 пациента с прижизненно и (или) посмертно подтвержденной новой коронавирусной инфекцией.Результаты и обсуждение. Установлено, что наибольшая доля умерших относится к группам пожилого (60-74 года) и старческого (75-90 лет) возрастов - 38% и 43% соответственно; умерших молодого возраста - 2 (34-44).При госпитализации у половины выявлялось поражение легких тяжелых степеней: КТ-3 и КТ-4 - в 31,1% и 28,5% соответственно, в остальных случаях поражение легкого прогрессировало уже в больнице. В работе приведены данные о средних сроках госпитализации, коморбидности, усредненные показатели клинического и биохимического анализов крови, результаты вскрытий. Установлено, что основным типом терминального состояния был легочный (79%), связанный с развитием острого респираторного дистресс-синдрома и нарастанием дыхательной недостаточности; у 19% умерших выявлен сердечный механизм смерти; в 2% случаев причиной смерти явилась общая интоксикация. Патогистологически в легких у умерших выявлены признаки различных фаз диффузного альвеолярного повреждения, а у пациентов, длительно находившихся на стационарном лечении, обнаруживали нарастающий фиброз легкого и патологическую регенерацию бронхиального и респираторного эпителиев. Продемонстрирован результат иммуно-гистохимического выявления N- и S-протеины вируса SARS-CoV-2 в клетках легкого.Заключение. В проведенном исследовании выявлены клинико-морфологические связи у пациентов с тяжелыми формами коронавирусной инфекции, установлен танатологический профиль при неблагоприятном течении...