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Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

Despite successful antiretroviral therapy (ART), patients infected with human immunodeficiency virus (HIV) can develop multi-class drug resistance (MDR). This retrospective study aimed to explore the prevalence of HIV-1 drug resistance over the past two decades by focusing on HIV-MDR and its predictors. ART-experienced patients with HIV with results from at least one plasma genotypic resistance test (GRT) from 1998 to 2018, from the Antiviral Response Cohort Analysis database, were included in this study. The temporal trend of resistance to any drug class was evaluated by considering all GRTs. Prevalence and predictors of HIV-MDR were analysed by consideration of cumulative GRTs. Among 15 628 isolates from 6802 patients, resistance to at least one drug class decreased sharply from 1998 to 2010 (1998-2001: 78%; 2008-2010: 59%; P < 0.001) and then remained relatively constant at approximately 50% from 2011 to 2018, with the proportion of isolates with HIV-MDR also stable (approximately 9%).By evaluating factors associated with cumulative HIV-MDR, the following factors were found to be associated with increased risk of HIV-MDR on multi-variate analysis: male gender; sexual and vertical transmission; number of previous protease inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-NRTIs; previous exposure to integrase strand transfer inhibitors, enfuvirtide and maraviroc; and co-infection with hepatitis B virus. In contrast, a nadir CD4 cell count >= 200 cells/mm3, starting first-line ART in 2008 or later and co-infection with hepatitis C virus were associated with lower risk of HIV-MDR. In conclusion, this study revealed that HIV-1 drug resistance has been stable since 2011 despite its dramatic decrease over the past two decades. HIV-MDR is still present, although at a lower rate, suggesting the need for continuous surveillance and accurate management of ART-experienced patients with HIV. (C) 2020 Elsevier Ltd and International Societ