The frequent finding of thrombocytopenia in patients with severe SARS-CoV-2 infection (COVID-19) and previous evidence that several viruses enter platelets suggest that SARS-CoV -2 might be internalized by platelets of COVID-19. Aim of our study was to assess the presence of SARS-CoV-2 RNA in platelets from hospitalized patients with aconfirmed diagnosis of COVID-19. RNA was extracted from platelets, leukocytes and serum from 24 COVID-19 patients and 3 healthy controls, real-time PCR and ddPCR for viral genes were carried out. SARS-CoV-2 RNA was not detected in any of the samples analyzed nor in healthy controls, by either RT-PCR or ddPCR, while RNA samples from nasopharyngeal swabs of COVID-19 patients were correctly identified. Viral RNA was not detected independently of viral load, of positive nasopharyngeal swabs, or viremia, the last detected in only one patient (4.1%). SARS-CoV-2 entry in platelets is not acommon phenomenon in COVID-19 patients, differently from other viral infections.

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GATA2 is a transcription factor with key roles in hematopoiesis. Germline GATA2 gene variants have been associated with several inherited and acquired hematologic disorders, including myelodysplastic syndromes. Among the spectrum of GATA2 deficiency-associated manifestations thrombosis has been reported in 25% of patients, but the mechanisms are unknown. GATA2 was shown to be involved in endothelial nitric oxide synthase (eNOS) regulation and vascular development. We assessed eNOS expression and angiogenesis in patients with GATA2-deficiency. Platelets and blood outgrowth endothelial cells (BOEC) from GATA2-variant carriers showed impaired NO-production and reduction of eNOS mRNA and protein expression and of eNOS activity. GATA2 binding to the eNOS gene was impaired in BOEC from GATA2-deficiency patients, differently from control BOEC. GATA2-deficiency BOEC showed also defective angiogenesis, which was completely restored by treatment with the NO-donor S-nitroso-N-acetylpenicillamine (SNAP). Atorvastatin, but not resveratrol, largely restored eNOS expression, NO biosynthesis and neoangiogenesis in GATA2-deficient BOEC by a mechanism involving increased expression of the eNOS transcription factor AP-1/c-JUN, replacing GATA2 when the latter is inactive. Our results unravel a possible thrombogenic mechanism of GATA2 mutations, definitely establish the regulation of eNOS by GATA2 in endothelial cells and show that endothelial angiogenesis is strictly dependent on the eNOS/NO axis. Given the ability of atorvastatin to restore NO production and angiogenesis by GATA2-deficient endothelial cells, the preventive effect of atorvastatin on thrombotic events and possibly on other clinical manifestations of the syndrome related to deranged angiogenesis should be explored in patients with GATA2-deficiency in an ad hoc designed clinical trial.

Background. This study aims to evaluate the effects of HYADD 4-G, a not chemically cross-linked HA (Hyaluronic Acid) derivative, and hylan G-F 20, a cross-linked HA product, on synovial matrix metalloproteinases and cytokines in patients suffering from knee osteoarthritis. Methods. 31 patients were randomized to receive HYADD 4-G or hylan G-F 20. Synovial fluid was collected before and one week after the first injection. Activity of MMP-3, MMP-2, MMP-13, IL-6 and other cytokines were measured. Changes in synovial fluid neutrophils and lymphocytes were analyzed. The VAS, the WOMAC questionnaire, and a Physician Global Assessment (PhGA VAS) were recorded. Results. A trend towards a greater decrease in MMP-3 activity was observed in the Hymovis ® group. Active MMP-2 and MMP-13 decreased in both groups. IL-6 levels also decreased significantly in both groups. Median change in neutrophils from baseline was significantly different between the treatment groups. No differences between the treatment groups were observed for the WOMAC, VAS and PhGA VAS scores. No serious adverse events were reported. Conclusions. These findings demonstrate that intra-articular HA injections in patients with knee osteoarthritis tend to protect cartilage structural integrity reducing the activity of key proteolytic enzymes implicated in cartilage degradation as well as inflammatory mediators.