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THE ROLE OF HMGB1 IN THE IMMUNE RESPONSE TO SARS-COV-2 INFECTION: FROM PATHOGENESIS TOWARDS A NEW POTENTIAL THERAPEUTIC TARGET

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the most important emerging pathogen since it was discovered in late 2019, infecting millions of people worldwide. The human body's defence against this new viral respiratory infection depends on the immune response of each person with a crucial impact on the appearance of clinical signs. Therefore, it is important to identify endogenous molecules with a fundamental role in severe pulmonary inflammation associated with SARS-CoV-2 infection. The impact of high mobility group proteins (HMGBs) in the pathogenesis of coronavirus disease 2019 (COVID-19) was recently proposed. There is also recent evidence that HMGBs, particularly HMGB1–2, play important roles in the replication of viral genomes. Moreover, HMGB1–4 proteins appear to be associated with inflammatory processes in the pathogenesis of many other viral diseases and disorders, including lung disease, ischemia-reperfusion-injury, sepsis, coagulopathy, trauma, neurological disorders, and cancer. This article presents the possible roles of HMGB1 in SARS-CoV-2 replication and its involvement in the pathogenesis of clinical severe pulmonary manifestations;these data can be useful in further virologic studies and the finding of new potential therapeutic targets in COVID-19.

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KEY POINTS IN FERTILITY PRESERVATION TREATMENT STRATEGIES DURING COVID-19 PANDEMIC. AN UPDATE ON PHARMACOLOGICAL THERAPIES

The fertility preservation (FP) field has developed in the two decades and offers women the possibility to have genetic children at some point in life. Fertility preservation is urgent by definition, performed for social reasons or medical indications, such as impending gonadotoxic therapy or radical gynaecological surgery. One year after the pandemic was declared, the COVID-19 infection imposed several restrictions and limited access to health care for the infertile couple. Ovarian stimulation is a pharmacological treatment used to induce the development of ovarian follicles;FP guidelines provide different options for ovarian stimulation. We performed a systematic search on fertility preservation (FP) procedures during the COVID-19 pandemic using the keywords: FP, ovarian stimulation, assisted reproduction techniques (ART), and COVID-19. In order to update the different treatment strategies in ovarian stimulation on fertility preservation studied in the last ten years, we searched for randomized clinical trials (RCTs) focused on therapeutic agents used in current protocols, gonadotropins, gonadotropin releasing hormone (GnRH), clomiphene citrate (CC), letrozole, androgens, metformin, tamoxifen, glucocorticoids, aspirin, coenzyme Q10, and sildenafil. Fertility may be influenced by SARS-CoV-2 infection - especially in men;until more evidence confirms the effects on fertility, patients with COVID-19 positive should delay FP procedures if possible. Access to fertility conservation services decreased during the analysed period due to the medical services restrictions and the reorientation of medical resources on patients with COVID-19, without major changes in the current therapeutic protocols. In terms of pharmacotherapy in ovarian stimulation (OS) procedures, letrozole is first line therapy, superior to CC for OS. Similar ovulation and pregnancy rate can be obtained in letrozole - induced ovulation compared to gonadotropin protocol. Adjuvant therapies may be used for OS but lack proven efficacy. Further studies on adjuvant therapies and complementary support are needed, to ensure optimal condition in assisted reproductive interventions for fertility preservation, especially in gonadotoxic therapies.

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