Humoral Immune Response after COVID-19 mRNA Vaccination in Patients with Liver Cirrhosis: A Prospective Real-Life Single Center Study.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (ß = -0.32 [-0.64, -0.04], p = 0.027) and past-HCV-infection (ß = -0.31 [-0.59, -0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1.

BACKGROUND: COVID-19 can cause multiple organ damages as well as metabolic abnormalities such as hyperglycemia, insulin resistance, and new onset of diabetes. The insulin/IGF signaling pathway plays an important role in regulating energy metabolism and cell survival, but little is known about the impact of SARS-CoV-2 infection. The aim of this work was to investigate whether SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the host cell/tissue, and if so, the potential mechanism and association with COVID-19 pathology. METHODS: To determine the impact of SARS-CoV-2 on insulin/IGF signaling pathway, we utilized transcriptome datasets of SARS-CoV-2 infected cells and tissues from public repositories for a wide range of high-throughput gene expression data: autopsy lungs from COVID-19 patients compared to the control from non-COVID-19 patients; lungs from a human ACE2 transgenic mouse infected with SARS-CoV-2 compared to the control infected with mock; human pluripotent stem cell (hPSC)-derived liver organoids infected with SARS-CoV-2; adipose tissues from a mouse model of COVID-19 overexpressing human ACE2 via adeno-associated virus serotype 9 (AAV9) compared to the control GFP after SARS-CoV-2 infection; iPS-derived human pancreatic cells infected with SARS-CoV-2 compared to the mock control. Gain and loss of IRF1 function models were established in HEK293T and/or Calu3 cells to evaluate the impact on insulin signaling. To understand the mechanistic regulation and relevance with COVID-19 risk factors, such as older age, male sex, obesity, and diabetes, several transcriptomes of human respiratory, metabolic, and endocrine cells and tissue were analyzed. To estimate the association with COVID-19 severity, whole blood transcriptomes of critical patients with COVID-19 compared to those of hospitalized noncritical patients with COVID-19. RESULTS: We found that SARS-CoV-2 infection impaired insulin/IGF signaling pathway genes, such as IRS, PI3K, AKT, mTOR, and MAPK, in the host lung, liver, adipose tissue, and pancreatic cells. The impairments were attributed to interferon regulatory factor 1 (IRF1), and its gene expression was highly relevant to risk factors for severe COVID-19; increased with aging in the lung, specifically in men; augmented by obese and diabetic conditions in liver, adipose tissue, and pancreatic islets. IRF1 activation was significantly associated with the impaired insulin signaling in human cells. IRF1 intron variant rs17622656-A, which was previously reported to be associated with COVID-19 prevalence, increased the IRF1 gene expression in human tissue and was frequently found in American and European population. Critical patients with COVID-19 exhibited higher IRF1 and lower insulin/IGF signaling pathway genes in the whole blood compared to hospitalized noncritical patients. Hormonal interventions, such as dihydrotestosterone and dexamethasone, ameliorated the pathological traits in SARS-CoV-2 infectable cells and tissues. CONCLUSIONS: The present study provides the first scientific evidence that SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in respiratory, metabolic, and endocrine cells and tissues. This feature likely contributes to COVID-19 severity with cell/tissue damage and metabolic abnormalities, which may be exacerbated in older, male, obese, or diabetic patients.

Male sex rather than socioeconomic vulnerability as a determinant for COVID-19 death in Sao Paulo: A population-based study.

Objectives: To determine the role of the male sex as a risk factor for coronavirus disease deaths in Sao Paulo and to what extent socioeconomic vulnerability and individual health issues can interfere in such risk. Methods: The primary cause of death, age, sex, comorbidities, and code of the Human Development Units of the residence of 37,583 individuals in Sao Paulo, Brazil, were obtained from the records on confirmed coronavirus disease resident hospitalizations of the city of Sao Paulo from the National Influenza Surveillance Information System. A social vulnerability index was assigned to each Human Development Unit. Using "death" as the outcome variable and sex, admission to the intensive care unit, obesity, renal and heart diseases, diabetes, and social vulnerability as confounders, the odds of death for males and females were compared via logistic regression. Results: The odds of death for males were 1.242 (confidence interval 95% = 1.237, 1.247) times the corresponding odds for females with the same values for all confounders. We estimated the odds of death for patients living in regions with high social vulnerability as 2.243 (CI 95% = 2.151, 2.339) times the corresponding odds of patients living in regions with very low social vulnerability with the same values of the remaining variables. Conclusion: The male:female death ratio by severe acute respiratory syndrome coronavirus 2 infection in Sao Paulo cannot be attributed only to comorbidities or social vulnerabilities. Our results suggest that the male sex is an independent biological risk factor for coronavirus disease death. Besides sex-specific factors, further research should focus on crucial biological factors in male sex coronavirus disease mortality.

Gender Differences in Takotsubo Syndrome.

BACKGROUND: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized. OBJECTIVES: The aim of the present study is to describe TTS sex differences. METHODS: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger. RESULTS: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52). CONCLUSIONS: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

Does SARS-CoV-2 Affect Male Urogenital System?

BACKGROUND: Widely known facts about Sars-Cov-2 infection's impact on urogenital system may play a relevant role in under-standing, diagnosing, and preventing male urological disorders. Sars-CoV-2 attacks the vascular endothelium of the entire organism; therefore, infection complications are visible in various organs. Relatively small number of original studies are available on Sars-CoV-2 infection and the effect on the reproductive system and fertility in men. The vast majority of publications focus only on discussing the effects of COVID-19 infection on just one aspect of male urology or fertility. OBJECTIVES: The aim of this review was to present the current understanding of the effects of COVID-19 infection on the male genitourinary system in the context of nephrological and reproductive system complications in men, considering the potential pathomechanisms causing significant nephrological disorders in the course of viral infection, as well as long-term effects of Sars-CoV-2 infection. We tried to make clinicians aware of urogenital complications in the course of COVID-19 occurrence and encourage them to create preventive procedures. METHODS: The article presented has been classified by us as "review". Of course, when searching for publications and making their critique, we focused primarily on the words: "Sars-CoV-2", "male urogenital system", "male infertility", "lower urinary tract symptoms". Therefore, there was no explicit and rigorous work selection methodology. Search strategies were based on the experience of the authors of the work. In order to select articles for the systematic review, literature searches were conducted on PubMed (https://pubmed.ncbi.nlm.nih.gov) using the following keywords: "Sars-CoV- 2" AND "male urogenital system" OR "male infertility" The search results were retrieved and manually screened for duplicate removal. Then abstracts and titles were checked for relevance. The articles were selected if they met the following inclusion criteria: human studies, focus on Sars-CoV-2 and male urogenital system or male infertility, published from 2020 to 2021, written in English, free full-text available. We included clinical trials, meta-analyses, randomized controlled studies, reviews, systematic reviews. RESULTS: After the literature search, a total of 267 articles were retrieved, including 153 reviews, 53 systematic reviews, and 61 original articles. Eventually, after abstract and title screening, 2 original articles, 29 reviews, and 8 systematic reviews were accepted. In our review paper, we presented data from 2 systematic reviews, 17 reviews, 2 meta-analyses, 1 case study, and 18 original articles, including 3 animals studies, 2 in vitro studies, and 14 human studies. CONCLUSION: Serious concerns for urologists among COVID-19 patients should be mainly orchitis, male infertility, priapism, erectile dysfunction, and lower urinary tract symptoms. It seems that the conclusions drawn should be treated with caution because, as mentioned above, in a pandemic, urinary complications are underdiagnosed and there are too few clinical trials and case reports.

Association of COVID-19 with Hepatic Injury Prevalence and Associated Factors

Background: Novel Coronavirus Disease 19 (COVID-19) was reported by the WHO as a pandemic in March 2020. It was associated with liver injury in up to 50% of patients. This retrospective cohort study investigated the prevalence and associated factors of liver injury among COVID-19 patients. Methods: We include 2319 consecutive COVID-19 patients from April 2020 to November 2020. Liver function tests were performed at baseline, 24–48 h after admission, and before mortality/discharge. We compared Saudis and non-Saudis, in admission rate, serum ALT level, morbidity, and mortality. Serum ALT was compared between sexes, admitted and non-admitted patients, and the deceased and survivors. Results: Men (1356;58.5%) and non-Saudis (1328;57.3%) were predominant. The mean (SD) age was 41.67 ± 18.3 years (18-100). One-third of the patients had comorbidities, and 1022 (44.1%) required hospital admission. Intensive Care Unit (ICU) transfer was required in 185/1022 (18%). Male and non-Saudis were most likely to be transferred to the ICU (P < 0.001). Hepatocellular liver injury was found in 797 (34.4%) patients. Male and admitted patients were more likely to have a hepatic injury (P = 0.001). The mortality rate among admitted patients was 17.8% (182/1022). Mortality was associated with older age and hepatic injury (P < 0.001 and P = 0.004, respectively). Conclusions: COVID-19 associated liver injury is common and it is associated with morbidity and mortality. © 2021, Author(s).

Ferritin level: A predictor of severity and mortality in hospitalized COVID-19 patients.

INTRODUCTION: This study aims to investigate in-hоsрitаl mоrtаlity in severe асute resрirаtоry syndrоme соrоnаvirus 2 Ñ€Ð°tients strаtified by serum ferritin levels. METHODS: Patients were stratified based on ferritin levels (ferritin levels ≤ 1000 or >1000). RESULTS: Approximately 89% (118) of the patients with ferritin levels > 1000 had pneumonia, and 51% (67) had hypertension. Fever (97, 73.5%) and shortness of breath (80, 61%) were two major symptoms among the patients in this group. Logistic regression analysis indicated that ferritin level (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.21-0.62; p < .001), male sex (OR = 2.63, 95% CI = 1.43-5.06; p = .003), hypertension (OR = 4.16, 95% CI = 2.42-7.36; p < .001) and pneumonia (OR = 8.48, 95% CI = 3.02-35.45; p < .001) had significance in predicting in-hospital mortality. Additionally, the Cox proportional hazards analysis and Kaplan-Meier survival probability plot showed a higher mortality rate among patients with ferritin levels > 1000. CONCLUSION: In this study, higher levels of serum ferritin were found to be an independent predictor of in-hоsрitаl mоrtаlity.

Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area - a population-based registry study.

BACKGROUND: Men reportedly suffer from a more severe disease and higher mortality during the global SARS-CoV-2 (Covid-19) pandemic. We analysed sex differences in a low epidemic area with low overall mortality in Covid-19 in a population based setting with patients treated in specialized healthcare. METHODS: We entered all hospitalized laboratory-confirmed Covid-19 cases of all specialized healthcare hospitals of the Capital Province of Finland, into a population-based quality registry and described demographics, severity and case-fatality by sex of the first Covid-19 wave February-June 2020. RESULTS: Altogether 5471 patients (49% male) were identified. Patients hospitalized in the specialist healthcare (N = 585, 54% male, OR 1.25; 95% CI 1.05-1.48) were of the same age. Men had less asthma and thyroid insufficiency and more coronary artery disease compared to women. Mean time from symptom onset to diagnosis was at least one day longer for men (p=.005). Men required intensive care unit (ICU) more often (27% vs. 17%) with longer lengths-of-stays at ICU. Male sex associated with significantly higher case-fatality at 90-days (15% vs. 8%) and all excess male deaths occurring after three weeks from onset. Men with fatal outcomes had delays in both Covid-19 testing and hospital admission after a positive test. The delays in patients with the most severe and fatal outcomes differed markedly by sex. In multivariable analysis, male sex associated independently with case-fatality (OR 2.37; 95% CI 1.22-4.59). CONCLUSIONS: Male sex associated with higher disease severity and case-fatality. Late presentation of male fatal cases could represent different treatment-seeking behaviour or disease progression by sex.