Polypharmacy Management in a Gender Perspective: At the Heart of the Problem: Analysis of Major Cardiac Diseases, SARS-CoV-2 Affection and Gender Distribution in a Cohort of Patients in Internal Medicine Ward.

BACKGROUND: COVID-19 patients with any pre-existing major cardio-vascular disease (CVD) are at the highest risk of viral infection and of developing severe disease. The pathophysiological mechanism is characterized by the viral link to angiotensin-converting enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and the inflicting of direct damage to the myocardium, the induction of microthrombosis, and the initiation of alterations in oxygen diffusion. The aim of the study is to analyze the clinical course and outcomes in patients (gender-stratified) with pre-existing major CVD. METHODS: Out of the 1833 (973 M/860 F) patients admitted to the Internal Medicine COVID-19 Unit of "Castelli Hospital", Lazio, Italy, from 1 January 2021 to 31 December 2021, 600 patients (320 M/280 F) with a mean age of 77 (78.6 M/75.1 F) previously had CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. RESULTS: All of the CVD COVID-19 patients underwent non-invasive ventilation (NIV). CVD was linked with increased LOS (21 days F/22 M) compared to no CVD (19 days). In total, 32.7% of total patients had major CVD. CONCLUSIONS: Timely identification and evaluation of patients with pre-existing major CVD are fundamental for adequate treatment based on gender, severity, state of illness and for risk reduction.

COVID-19 and Frailty.

Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older age is also associated with decreased kidney function and is consequently associated with an increased risk of cardiovascular disease. All of this in the course of COVID-19 infection can worsen and promote the progression of chronic kidney damage and all its sequelae. Frailty is a condition characterized by the decline in function of several homeostatic systems, leading to increased vulnerability to stressors and risk of adverse health outcomes. Thus, it is very likely that frailty, together with comorbidities, may have contributed to the high vulnerability to severe clinical manifestations and deaths from COVID-19 among older people. The combination of viral infection and chronic inflammation in the elderly could cause multiple unforeseen harmful consequences, affecting overall disability and mortality rates. In post-COVID-19 patients, inflammation has been implicated in sarcopenia progression, functional activity decline, and dementia. After the pandemic, it is imperative to shine a spotlight on these sequelae so that we can be prepared for the future outcomes of the ongoing pandemic. Here, we discuss the potential long-term consequences of SARS-CoV-2 infection and its possibility of causing permanent damage to the precarious balance existing in the frail elderly with multiple pathologies.

Ferritin as prognostic marker in COVID-19: the FerVid study.

BACKGROUND: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients. METHODS: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit. RESULTS: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count. CONCLUSION: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.

Arterial Hypertension and Diabetes Mellitus in COVID-19 Patients: What Is Known by Gender Differences?

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected >160 million people around the world. Hypertension (HT), chronic heart disease (CHD), and diabetes mellitus (DM) increase susceptibility to SARS-CoV-2 infection. AIMS: We designed this retrospective study to assess the gender differences in hypertensive diabetic SARS-CoV-2 patients. We reported data, by gender differences, on the inflammatory status, on the hospital stays, intensive care unit (ICU) admission, Rx and CT report, and therapy. METHODS: We enrolled 1014 patients with confirmed COVID-19 admitted into different Hospitals of Campania from 26 March to 30 June, 2020. All patients were allocated into two groups: diabetic-hypertensive group (DM-HT group) that includes 556 patients affected by diabetes mellitus and arterial hypertension and the non-diabetic- non-hypertensive group (non-DM, non-HT group) comprising 458 patients. The clinical outcomes (i.e., discharges, mortality, length of stay, therapy, and admission to intensive care) were monitored up to June 30, 2020. RESULTS: We described, in the DM-HT group, higher proportion of cardiopathy ischemic (CHD) (47.5% vs. 14.8%, respectively; p < 0.0001) and lung diseases in females compared to male subjects (34.8% vs. 18.5%, respectively; p < 0.0001). In male subjects, we observed higher proportion of kidney diseases (CKD) (11% vs. 0.01%, respectively; p < 0.0001), a higher hospital stay compared to female subjects (22 days vs. 17 days, respectively, p < 0.0001), a higher admission in ICU (66.9% vs. 12.8%, respectively, p < 0.0001), and higher death rate (17.3% vs. 10.7%, respectively, p < 0.0001). CONCLUSION: These data confirm that male subjects, compared to female subjects, have a higher hospital stay, a higher admission to ICU, and higher death rate.

Viral Infection, COVID-19 in Pregnancy and Lactating Women: What Is Known?

Introduction. Viral infections during pregnancy have always been considered to cause complications and adverse events and birth defects during pregnancy. In particular, we do not have any therapeutic or preventive tools aimed at protecting the mother and fetus during the gestational period during pandemics. Methods. The studies were identified by using the PubMed database published until 30 April 2021. The search was performed by using the following keywords: viral infection, SARS-CoV-2, COVID-19, vaccine, pregnancy, gestational period, pandemics, vaccination, complication, adverse events, drugs. Results. It has been reported that viral infections are considered to cause complications and adverse events during pregnancy. In this regard, pregnancy is associated with higher mortality rates and complications during viral infections. In fact, maternal immunization represents a unique approach to protect newborns from several infectious diseases. Conclusion. European Board and College of Obstetrics and Gynecology (EBCOG) and International public health institutions (WHO, CDC) report the recommendations about the use of vaccines during pregnancy.

Immune system and COVID-19 by sex differences and age.

In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.

Gender differences in vaccine therapy: where are we in COVID-19 pandemic?

Vaccination is one of the greatest achievements of public health. Vaccination programs have contributed to the decline in mortality and morbidity of various infectious diseases. This review aims to investigate the impact of sex/gender on the vaccine acceptance, responses, and outcomes. The studies were identified by using PubMed, until 30th June 2020. The search was performed by using the following keywords: SARS-CoV-2, COVID-19, gender, sex, vaccine, adverse reaction. Clinical trials, retrospective and prospective studies were included. Studies written in languages other than English were excluded. Studies were included if gender differences in response to vaccination trials were reported. All selected studies were qualitatively analyzed. Innate recognition and response to viruses, as well as, adaptive immune responses during viral infections, differ between females and males. Unfortunately, a majority of vaccine trials have focused on healthy people, with ages between 18 to 65 years, excluding the elderly, pregnant women, post-menopausal female and children. In conclusion, it is apparent that the design of vaccines and vaccine strategies should be sex-specific, to reduce adverse reactions in females and increase immunogenicity in males. It should be mandatory to examine sex-related variables in pre-clinical and clinical vaccine trials, such as their crucial role for successful prevention of pandemic COVID-19.

Gender differences in treatment of Coronavirus Disease-2019.

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality.