Immuno-Endocrinology of COVID-19: The Key Role of Sex Hormones.

Epidemiological evidence shows clear gender disparities in the Coronavirus 2019 Disease (COVID-19) severity and fatality. This may reflect the contribution of gender-related factors, such as sex hormones, to COVID-19 pathogenesis. However, the mechanism linking gender disparities to COVID-19 severity is still poorly understood. In this review, we will pinpoint several elements involved in COVID-19 pathogenesis that are regulated by the two main sex hormones, estrogen and androgen. These include tissue specific gene regulation of SARS-CoV2 entry factors, innate and adaptive immune responses to infection, immunometabolism, and susceptibility to tissue injury by cytopathic effect or hyper-inflammatory response. We will discuss the mechanistic link between sex hormone regulation of COVID-19 pathogenetic factors and disease severity. Finally, we will summarize current evidence from clinical studies and trials targeting sex hormones and their signalling in COVID-19. A better understanding of the role of sex hormones in COVID-19 may identify targets for therapeutic intervention and allow optimization of treatment outcomes towards gender-based personalised medicine.

Vertebral fractures and mortality risk in hospitalised patients during the COVID-19 pandemic emergency.

BACKGROUND AND OBJECTIVE: Bone fragility has been linked to COVID-19 severity. The objective of this study was to evaluate whether a diagnosis of vertebral fracture (VF) increased mortality risk in COVID-19 patients and whether this effect was greater than in those without COVID-19. METHODS: We assessed VFs by computed tomography (CT) in a cohort of 501 patients consecutively admitted to the emergency department (ED) for clinical suspicion of SARS-CoV-2 infection during the first wave of pandemic emergency. Of those, 239 had a confirmed diagnosis of COVID-19. RESULTS: VF prevalence was similar between COVID-19 and non-COVID-19 groups (22.2 vs. 19%; p = 0.458). Death rates were similar between COVID-19 and non-COVID-19 groups at both 30 (15.8 vs. 12.2%; p = 0.234) and 120 days (21.8 vs. 17.6%; p = 0.236). The mortality risk was higher in COVID-19 patients either with one or multiple fractures compared to those without VFs, at 30 and 120 days, but statistical significance was reached only in those with multiple VFs (30-day HR 3.03, 95% CI 1.36-6.75; 120-day HR 2.91, 95% CI 1.43-5.91). In the non-COVID-19 group, the 30-day mortality risk was significantly higher in patients either with one (HR 7.46, 95% CI 3.12-17.8) or multiple fractures (HR 6.2, 95% CI 2.75-13.98) compared to those without VFs. A similar effect was observed at 120 days. After adjustment for age, sex and bone density, mortality risk remained associated with VFs in the non-COVID-19 group only. CONCLUSIONS: VFs were not independently associated with short-term mortality in patients with COVID-19, but they strongly increased mortality risk in those without COVID-19.

Spontaneous psoas haematoma: a life-threatening complication of anticoagulation in COVID-19. A case series of four episodes.

BACKGROUND: Anticoagulant prophylaxis is part of the standard management of hospitalized COVID-19 patients. Despite adequate thromboprophylaxis, one-third of COVID-19 patients with pneumonia developed pulmonary embolism. This high rate of thrombotic complications has led to higher doses of anticoagulants according to clinical complexity (e.g. intensive care unit (ICU) patients) and D-dimer levels. On the other side of the coin, haemorrhagic complications are being increasingly reported. CASES PRESENTATION: We herein report four cases of spontaneous psoas haematomas (SPH) among 548 patients hospitalized for SARS-CoV-2 pneumonia between March 2020 and January 2021 (incidence of 7.3 cases per 1000 patients). All patients had pneumonia, with age ranging between 62 and 83 years. All patients received anticoagulant therapy with low weight molecular heparin (100 U.I. anti-Xa/kg 2 times/d) from admission: in two cases, a diagnosis of pulmonary embolism was made. In another case, a thrombosis of left axillary and basilic veins was found, and only in one case anticoagulant therapy was started because of elevated levels of D-dimer. In all cases, signs of anaemia were detected and patients experienced low back or abdominal pain. The diagnosis of spontaneous psoas haematoma was made by computed tomography (CT) after a median of 12.5 d (9;16) from admission and 19.5 d (14.75; 24.25) from the beginning of COVID-19 symptoms. Half of these patients died from haemorrhagic shock. CONCLUSIONS: Given the potential life-threatening of SPH and the possible subtle clinical presentation, we believe it is crucial to raise clinicians awareness of this complication among COVID-19 patients undergoing anticoagulants.