In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

SummaryThree novel polymorphisms were found in the repeated region of the large exon 13 of factor V gene, one giving rise to a codon dimorphism (Serl240) and two causing aminoacid substitutions (Hisl299Arg, Leul257Ile). An increasing frequency of the Argl299 (R2 allele) correlated with a decreasing mean plasma factor V activity in the groups of subjects under study, which included 26 unrelated subjects with partial factor V deficiency. Family studies supported the co-inheritance both of low factor V activity and of R2 allele. The reduction of factor V activity associated with the R2 allele was not clinically symptomatic even in the homozygous condition and was characterized by a parallel reduction of antigen in plasma, in which abnormal molecules were not detected. Data suggest that the R2 allele represents a marker in linkage with an unknown defect rather than a functional polymorphism.These studies provide the first evidence of a genetic component in determining factor V levels in plasma and of a genetic linkage between the factor V gene and factor V deficiency. They also define specific haplotypes which are associated with factor V deficiency or with APC resistance (Arg506Gln) and are valuable fools for the study of factor V defects.

BACKGROUND Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden,FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. METHODS We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). RESULTS We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95% confidence intervals [CI]: 0.98–1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR=4.22; 95% CI: 3.35–5.32; and OR=2.79;95% CI: 2.25–3.46, respectively), in double hterozygotes (OR=3.42; 95%CI 1.64-7.13), and in homozygous FVL or PT20210A (OR=11.45; 95%CI: 6.79-19.29; and OR: 2.79; 95%CI: 2.25 – 3.46, respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤45 years (p-value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). CONCLUSIONS In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

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The results of this study show that EMF can act in concert with IGF-I in stimulating PG synthesis in bovine articular cartilage explants. As this effect is not maintained in chondrocyte monolayers, the native cell-matrix interactions in the tissue may be fundamental in driving the EMF effects. These data suggest that in vivo the combination of both EMF and IGF may exert a more chondroprotective effect than either treatment alone on articular cartilage.

The PR at entry affects response to GP IIb/IIIa inhibition, mechanical treatment, and long-term outcome in STEMI patients undergoing primary intervention.

The number of patients affected by primary CVD is so great that the vast majority of ulcers are also related to this common problem. On the other hand, there is not a reliable way for identifying in advance, from the broad base of primary CVD patients (20-40% of the general population), the high risk minority (10% of primary CVD cases) who will develop a venous ulcer. In such cases, a simple C282Y blood genetic test demonstrated an elevated specificity in predicting ulcer development (98%, CI 95%, 92.8-99.7). The genetic test could be applied starting from the C2 class, varicose veins, the most common situation observed in clinical practice. In perspective, the presence of the C282Y mutation would strengthen the indications and priorities for surgical correction of superficial venous insufficiency.

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