HLA-A*01:01 allele diminishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire.

In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules. In this study, we compared the features of the HLA-I genotype in symptomatic patients with COVID-19 in the first and third waves of the pandemic. As a result, we could identify the diminishing of carriers of the HLA-A*01:01 allele in the third wave and demonstrate the unique properties of this allele. Thus, HLA-A*01:01-binding immunoprevalent epitopes are mostly derived from ORF1ab. A set of epitopes from ORF1ab was tested, and their high immunogenicity was confirmed. Moreover, analysis of the results of single-cell phenotyping of T-cells in recovered patients showed that the predominant phenotype in HLA-A*01:01 carriers is central memory T-cells. The predominance of T-lymphocytes of this phenotype may contribute to forming long-term T-cell immunity in carriers of this allele. Our results can be the basis for highly effective vaccines based on ORF1ab peptides.

A Review of Recent Studies on the Effects of SARS-CoV-2 Infection and SARS-CoV-2 Vaccines on Male Reproductive Health.

According to world statistics, men are more susceptible to the coronavirus disease 2019 (COVID-19) than are women. Considering the interconnection between infections and male infertility, investigation of the potential impact of COVID-19 on men's reproductive health is now a particularly relevant topic. Published data indicate decreased sperm quality and orchitis development in patients with COVID-19, including reduced sperm count, decreased sperm motility, and elevated DNA fragmentation index. Although mass vaccination against COVID-19 is currently being carried out worldwide using available authorized vaccines, the effect of these vaccines on men's reproductive health has not yet been investigated. There is currently no evidence that SARS-CoV-2 can be transmitted in semen, but available data suggest that it can infect spermatogonia, spermatids, Leydig cells, and Sertoli cells. Therefore, SARS-CoV-2 orchitis and reduced male fertility may be long-term complications of COVID-19, which requires further investigation. Currently, there is also no evidence that vaccines against SARS-CoV-2 have any pathological effects on spermatogenesis or male reproductive health. Thus, further studies are needed to determine the effects of COVID-19 and COVID-19 vaccines on men's reproductive health, which will help to optimize the management and rehabilitation of these patients. This review aims to discuss recent studies on the impact of the COVID-19 and COVID-19 vaccines on men's reproductive health. The article addresses various issues such as the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on testosterone biosynthesis, semen parameters, testicular tissue, and epididymis.

COVID-19-associated inhibition of energy accumulation pathways in human semen samples.

OBJECTIVE: To investigate transcriptional alterations in human semen samples associated with COVID-19 infection. DESIGN: Retrospective observational cohort study. SETTING: City hospital. PATIENTS: Ten patients who had recovered from mild COVID-19 infection. Eight of these patients had different sperm abnormalities that were diagnosed before infection. The control group consisted of 5 healthy donors without known abnormalities and no history of COVID-19 infection. INTERVENTIONS: We used RNA sequencing to determine gene expression profiles in all studied biosamples. Original standard bioinformatic instruments were used to analyze activation of intracellular molecular pathways. MAIN OUTCOME MEASURES: Routine semen analysis, gene expression levels, and molecular pathway activation levels in semen samples. RESULTS: We found statistically significant inhibition of genes associated with energy production pathways in the mitochondria, including genes involved in the electron transfer chain and genes involved in toll-like receptor signaling. All protein-coding genes encoded by the mitochondrial genome were significantly down-regulated in semen samples collected from patients after recovery from COVID-19. CONCLUSIONS: Our results may provide a molecular basis for the previously observed phenomenon of decreased sperm motility associated with COVID-19 infection. Moreover, the data will be beneficial for the optimization of preconception care for men who have recently recovered from COVID-19 infection.

Radiology Diagnostics of a New Coronavirus Infection in Pregnant Women. Experience of O.M. Filatov Municipal Clinical Hospital No. 15, Moscow

Background. The pandemic of coronavirus pneumonia (COVID-19) is spreading globally at an accelerated rate and is a major health problem. The purpose of this study was to assess the possibility of using a combination of radiation diagnostic methods in lung lesions in pregnant women, with confirmed coronavirus infection and suspected COVID-19 pneumonia, hospitalized in O.M. Filatov Municipal Clinical Hospital No. 15, Moscow. Methods. Retrospectively analyzed changes in lung parenchyma and pleura detected by multispiral computed tomography of chest organs and pulmonary ultrasound in 90 pregnant patients with clinical manifestations of viral pneumonia and confirmed coronavirus infection. Results. Examined 90 patients with clinical manifestations of pneumonia and PCR-confirmed COVID-19. Among the clinical manifestations, coughing, fever, shortness of breath prevailed. Most changes detected by lung tomography (performed in 92% of patients), had a polysegmental and bilateral character, were more often localized in the peripheral departments, in 74 (89%) patients were involved in a pathological process of more than two lobes, in 77 (93%) of the patients were determined the centers of pulmonary tissue compaction by the type of “ground glass”, and the combination of the above manifestations with the presence of foci of consolidation and reticular changes was noted in 23 (28%) cases. Among the complications more common: thickening of the pleura, hydrothorax, less often pneumothorax. In 43 (48%) patients, MSCT was supplemented by ultrasound examination of the lungs and pleura, and in 21 (23%) patients, ultrasound was used in isolation as a dynamic control tool to reduce dose load and comply with the ALARA principle, while in 7 (8%) patients, ultrasound was used as the only diagnostic tool due to refusal to perform MSCT. Conclusion. Radiosemiotics of lung lesions in pregnant women with COVID-19, detected in MSCT of thoracic organs, does not differ from that in non-pregnant patients. The appearance of specific zones of pulmonary tissue compaction in the form of a “gound glass”, as a manifestation of a unilateral or bilateral, mono- or polyphocal lung lesion, is highly likely to indicate a manifestation of COVID-19. Pulmonary ultrasound also allows detecting characteristic changes in lung parenchyma and pleura in pregnant women, correlating with MSCT data, primarily in patients with medium-severe forms of pneumonia. Use of ultrasonography corresponds to the principle of ALARA in medicine, remaining a choice method with the women refusing the visualization interfaced to beam loading that can be used in the period of COVID-19 pandemic. Обоснование. Пандемия пневмонии, вызванной коронавирусной болезнью (COVID-19), распространяется во всем мире ускоренными темпами и является серьезной проблемой в области здравоохранения. Цель исследования - оценка возможности использования комбинации лучевых методов диагностики при поражении легких у беременных с подтвержденной коронавирусной инфекцией и подозрением на COVID-19-пневмонию, госпитализированных в Городскую клиническую больницу № 15 им. О.М. Филатова Департамента здравоохранения г. Москвы. Материалы и методы. Ретроспективно были проанализированы изменения паренхимы легких и плевры, выявленные с помощью мультиспиральной компьютерной томографии (МСКТ) органов грудной клетки и ультразвукового исследования легких, у 90 беременных пациенток с клиническими проявлениями вирусной пневмонии и подтвержденной коронавирусной инфекцией. Результаты. Обследовано 90 пациенток с клиническими проявлениями пневмонии и ПЦР-подтвержденным COVID-19. Среди клинических проявлений превалировали кашель, лихорадка, одышка. Большинство изменений, выявленных при томографии легких (выполнено у 92% пациенток), имели полисегментарный и двусторонний характер, чаще локализовались в периферических отделах, у 74 (89%) пациенток было вовлечено в патологический процесс больше двух долей, у 77 (93%) пациенток определялись очаги уплотнения легочной ткани по типу «матового стекла», а сочетание вышеуказанных проявлений с наличием очагов консолидации и ретикулярных изменений отмечалось в 23 (28%) случаях. Среди осложнений чаще встречались: утолщение плевры, гидроторакс, реже пневмоторакс. У 43 (48%) пациенток МСКТ было дополнено ультразвуковым исследованием легких и плевры, а у 21 (23%) пациенток УЗИ использовалось изолированно в качестве инструмента динамического контроля с целью снижения дозовой нагрузки и соблюдения принципа ALARA, при этом у 7 (8%) пациенток УЗИ использовалось как единственный инструмент диагностики из-за отказа от выполнения МСКТ. Заключение. Рентгеносемиотика поражений легких у беременных с COVID-19, выявленная при МСКТ органов грудной клетки, не отличается от таковой у небеременных пациенток. Появление специфических зон уплотнения легочной ткани в виде «матового стекла», как проявление одно- или двустороннего, моно- или полифокального поражения легких, с высокой вероятностью говорит о проявлении COVID-19. УЗИ легких также позволяет выявлять характерные изменения паренхимы легких и плевры у беременных, коррелируя с данными МСКТ в первую очередь у пациенток со среднетяжелыми формами пневмонии. Использование УЗИ соответствует принципу ALARA в медицине, оставаясь методом выбора у женщин, отказывающихся от визуализации, сопряженной с лучевой нагрузкой, что может быть использовано в период пандемии COVID-19.