Mechanisms of SARS-CoV-2 virus effects on prostate tissues, including associations with patient hormonal state and postvaccination reactions

Nowadays, the most notable negative effects of SARS-CoV-2 are the pulmonary manifestations as well as cardiovascular system damage. Evaluation of postvaccination changes in the male reproductive system and analysis of their mechanisms seem to be important because of their direct effect on fertility. Thus, it may play a significant role in perspective. Studies based on the application of fluorescence in situ hybridization showed that most acini epithelial cells, as well as some mesenchymal and endothelial cells were positive for SARS-CoV-2 RNA. As for co-expression of the ACE2 cell receptor and the serine protease TMPRSS2, which the virus uses to enter cells, it was also detected in most prostate epithelial and stromal cells. The mechanism of prostate damage in COVID-19 may also be related to dysregulation of the renin-angiotensin system. Increased levels of angiotensin-2 secretion in the prostate in patients with benign prostatic hyperplasia may increase the effect of the virus directly on the cells of the organ. These mechanisms may explain the elevated serum prostatic specific antigen levels in patients with benign prostatic hyperplasia during the active period of COVID-19. Non-specific mechanism of prostate damage is connected with coagulopathy development – thrombosis of venous plexus and hemodynamic disturbances, which can cause secondary damage of parenchyma. There is a definite relationship between the hormonal status of the patient and the severity of the infection – low levels of both testosterone and dihydrotestosterone contribute to the development of severe complications in patients infected with SARS-CoV-2. The possibility of using testosterone drugs in patients with hypogonadism and COVID-19 as an alternative treatment option – to suppress the cytokine storm phenomenon – is being considered. Patients with a history of prostate cancer, with localized prostate cancer in the absence of metastases participated in vaccine studies – among the side effects of vaccination in several cases only regional lymphadenopathy on the injection side of the drug was noted. © 2022 ABV-Press Publishing House. All rights reserved.

Prospective two-arm study of fertility in men with COVID-19

Introduction & Objectives: COVID-19 infection is hypothesized to have a potentially negative effect on male fertility through direct damage to the testes. The current trial is aimed at investigating the effect of SARS-CoV-2 on fertility and determining if viral bodies directly damage testicularfunction.Materials & Methods: This prospective study included controls comprising healthy participants and cases of patients suffering from pneumoniabased on chest CT and a positive of SARS-CoV-2 throat swab exhibited only moderate symptoms in accordance with the WHO classification.Extensive epidemiological, clinical, laboratory (hormonal levels, etc.) and ultrasound data (color doppler ultrasound of the scrotum) were collected. Asperm examination was performed in cases during their COVID-19 related hospital stay and 3 months after the discharge home. We also assessedthe testicles of COVID-19 patients who died of their disease (n=20) obtained during autopsies.Results: A total of 88 participants were included (44 controls and 44 cases). Blood testosterone levels were below normal (local reference values,5-50 nmol/ml) in 27.3% of the cases (12/44). The mean level (7.3±2.7 nmol/ml) was lower than that in the healthy controls (13.5±5.2 nmol/ml,p<0.001). At 3 months after discharge, the level returned to normal (13.7±4.5 nmol/ml) and was no different from that of the controls. An increase inLH and FSH was also detected compared to the healthy controls (p=0.047 and p=0.002). The spermogram revealed decreased motility in COVID-19patients (p=0.001), and higher number of immobile sperm (during COVID-19 – 58.8% and at 3 months 47.4%, p=0.005). All these parametersreturned to normal at 3 months after discharge. As for pathology findings, in the majority of autopsies (18/20) structural disorders of the testiculartissue, with signs of damage to germ cells were observed.Conclusions: COVID-19 and its treatment significantly affect hormone levels and sperm quality during the disease. Postmortem examinationconfirms inflammation and viral infiltration of the testicles. However, in those who had moderate to severe disease, decline in hormone levels andsperm quality was transient with values returning to baseline at 3 months

Asthma may influence long-term consequences of COVID-19 in hospitalised adult

Background: The symptoms of the COVID-19 acute phase are well studied, but the long-term sequelae (post-COVID condition) are still poorly characterised. The aim of this study was to evaluate the prevalence of persistent symptoms in previously hospitalised adult patients with COVID-19 and assess risk factors for the post-COVID condition Method: Ambidirectional cohort study of patients over 18 years hospitalised to Sechenov University Hospital Network, Moscow, Russia with clinically diagnosed or laboratory-confirmed COVID-19 between April 8 and July 10, 2020. Study participants were interviewed 6-8 months after discharge via telephone using a follow-up case report form (CRF) developed by ISARIC in collaboration with WHO. Identified symptoms were categorised according to organ systems. Risk factors were assessed by multivariate logistic regression. Results: Among 4,755 patients discharged from the hospitals, 2,649 were subsequently interviewed. The median age of patients was 56 years (46-66), and 1,353 patients (51.1%) were female. The follow-up median time was 217.5 days (200.4-235.5). 1,247 (47.1%) participants reported persistent symptoms (since discharge). The most frequent symptoms were fatigue (21.2%, 551/2599), shortness of breath (14.5%, 378/2614) and forgetfulness (9.1%, 237/2597). Female gender was associated with chronic fatigue with an odds ratio of 1.67 (95% confidence interval 1.39-2.02), neurological 2.03 (1.60-2.58), mental 1.83 (1.41-2.40), respiratory 1.31 (1.06-1.62) and dermatological symptoms 3.26 (2.36-4.57), GI disturbances 2.50 (1.64-3.89) and sensory problems 1.73 (2.06-2.89). Pre-existing asthma was associated with a higher risk of neurological 1.95 (1.25-2.98) and mood and behavioural changes 2.02 (1.24-3.18). Conclusion: Six to eight months after COVID-19 nearly half of patients have symptoms lasting since discharge. The main risk factor for the majority of the development of long-term symptoms was female sex. Asthma may also serve as a risk factor for the post-COVID condition. Further follow-up of patients reporting the persistence of COVID-19 symptoms and the development of interventional approaches for the prevention of post-COVID manifestations are needed.

Clinical outcomes of patients with COVID-19 admitted for respiratory support to the intensive care units in Russia

Aim. To evaluate mortality and risk factors for death in patients with COVID-19 who required admission to intensive care units (ICU) for respiratory support in Russia.Material and methods. In a retrospective study, we collected medical records of the consecutive ICU patients submitted by the local COVID-19 hospitals across Russia to the Federal Center at the Sechenov University (Moscow) betweenMarch 16 to May 3, 2020. All patients have completed their hospital stay (death or recovery). Diagnosis of SARS-CoV-2 pneumonia was established both by polymerase chain reaction (PCR) and CT. In patients with inconclusive or negative results of PCR, the SARS-CoV-2 pneumonia was defined as severe acute respiratory infection with typical CT findings and no other obvious aetiology. We used Cox proportional hazards regression model adjusted for age, sex and other risk factors to estimate hazard ratios (HR) and 95% confidence intervals (CI).Results. We studied 1522 ICU patients with SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), including 864 males and 658 females at the median age of 62 years. Nine hundred twenty two records (60.1%) were submitted from Moscow and Moscow province, and 600 records (39.4%) were received from the hospitals located in 70 regions of Russia. SARS-CoV-2 was verified by PCR in 995 (65.4%) patients. Among 1522 patients enrolled in the study,995 patients (65.4%) died, and 527 (34.6%) patients recovered. The most common causes of death were ARDS (93.2%), cardiovascular events (3.7%) and pulmonary embolism (1.0%). The mortality rate was low in patients with less severe pneumonia requiring oxygen therapy (10.1%). However, it increased significantly in patients who were placed on noninvasive or invasive ventilation (36.8% and 76.5%, respectively). Risk of death increased with age, and in males older than 50 years it was significantly higher than in females of similar age. In a unvariate analysis, arterial hypertension, coronary artery disease (CAD), history of stroke, atrial fibrillation, type 2 diabetes, obesity and malignancies were associated with an increased risk of death. However, only CAD (HR1.257, 95% CI 1.064-1.485, p=0.007), type 2 diabetes (HR1.300, 95% CI 1.131-1.494, p<0.0001) and obesity (HR1.347,95% CI 1.166-1.556, p<0.0001) retained statistical signicance in multiple factor analysis.Conclusion. In ICU patients with COVID-19, severity ofARDS (i.e. requirement in mechanical ventilation), age, malegender, CAD, obesity and type 2 diabetes were associatedwith a higher risk of death. Цель. Изучение летальности и факторов рискасмерти больных с COVID-19, госпитализированных для респираторной поддержки в отделения реанимации и интенсивной терапии(ОРИТ) лечебных учреждений Российской Федерации.Материал и методы. Ретроспективноеисследование было выполнено в Федеральномдистанционном консультативном центре анестезиологии и реаниматологии для взрослыхпациентов с COVID-19 на базе Первого МГМУим. И.М. Сеченова. В исследование включаливсех пациентов с известными исходами (смертьот любых причин или выздоровление) SARS-CoV-2 пневмонии, осложнившейся острым респираторным дистресс синдромом (ОРДС),которые были проконсультированы с 16 мартапо 3 мая 2020 г. Факторы риска смерти анализировали с помощью многофакторной регрессионной модели Кокса.Результаты. В исследование были включены 1522 пациента, 864 (56,8%) мужчины и 658(43,2%) женщин. Медиана возраста - 62 года.922 (60,6%) больных находились в ОРИТ стационаров Москвы и Московской области, 600(39,4%) - лечебных учреждений в 70 регионахРоссийской Федерации. У 995 (65,4%) больных диагноз SARS-CoV-2 инфекции был подтвержден с помощью ПЦР. Умерли 995 (65,4%)пациентов, выжили 527 (34,6%). Основнымипричинами смерти были ОРДС (93,2%), сердечно-сосудистые осложнения (3,7%) и тромбоэмболия легочной артерии (1,0%).Летальность была низкой у пациентов, находившихся на оксигенотерапии (10,1%), изначительно повышалась у больных, которыхприходилось переводить на неинвазивную(36,8%) или инвазивную (76,5%) вентиляциюлегких. Риск смерти увеличивался с возрастоми в возрастных группах старше 50 лет у мужчинбыл достоверно выше, чем у женщин. В однофакторных моделях заболеваниями, ассоциировавшимися с развитием летального исхода,были артериальная гипертония, ИБС, инсульт,фибрилляция предсердий, сахарный диабет 2типа, ожирение и солидные опухоли, однако вмногофакторной модели, построенной по всемпризнакам с коррекцией по полу и возрасту,статистическое значение сохранили толькоИБС (отношение рисков [ОР] 1,257, 95% доверительный интервал [ДИ] 1,064-1,485,p=0,007), сахарный диабет 2 типа (ОР 1,300,95% ДИ 1,131-1,494, p<0,0001) и ожирение(ОР 1,347, 95% ДИ 1,166-1,556, p<0,0001).Заключение. Основными факторами рискасмерти больных с COVID-19, переведенных вОРИТ для респираторной поддержки, былитяжесть ОРДС, прежде всего необходимость вИВЛ, пожилой возраст, мужской пол, а такжеИБС, ожирение и сахарный диабет 2 типа.

[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.