Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study.

Background: Severity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified. Methods: We used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups. Results: We enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO. Conclusions: Hypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.

Role of HPV vaccination for prevention of male infertility.

Infertility is an important health problem affecting about 16% of couples worldwide and male infertility is responsible for about 50% of the cases. Among the causes, sexually transmittable infections (STI) are widely accepted by researchers as etiological factors of male infertility and their incidence is growing. In detail, several reports documented the presence of HPV in semen from infertile patients. In these cases, HPV DNA was bound to the sperm surface and played a role in the infertility by affecting many sperm parameters. Despite a safe and highly effective vaccine is currently available to prevent HPV infection, there are still no effective treatments to completely clear the virus. However, recent studies highlighted that HPV vaccination can be an effective tool to counteract HPV seminal infection even in already infected patients. In fact, it seems able to reduce the viral time to clearance and the relapse of infection in males with persistence of HPV in semen. In this review, we aimed to explore, in a narrative way, currently available literature about HPV infection of male genital tract and the mechanisms by which HPV virions may alter sperm parameters and, therefore, male fertility, both natural and assisted. Moreover, we aimed to report and discuss the most recent evidence about the role of HPV vaccine administration as a therapeutic tool in males with persistent HPV seminal infection.

Is HPV the Novel Target in Male Idiopathic Infertility? A Systematic Review of the Literature.

Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for about 50% of the cases, and the various causes of male infertility may be classified in pre-testicular (for example hypothalamic diseases), testicular, and post-testicular (for example obstructive pathologies of seminal ducts) causes. Sexually transmitted infections (STI) are increasingly widely accepted by researchers and clinicians as etiological factors of male infertility. In particular, several recent reports have documented the presence of HPV in seminal fluid and observed that sperm infection can also be present in sexually active asymptomatic male and infertile patients. In this review, we aimed to perform a systematic review of the whole body of literature exploring the impact of HPV infection in natural and assisted fertility outcomes, from both an experimental and a clinical point of view. Starting from in-vitro studies in animals up to in-vivo studies in humans, we aimed to study and evaluate the weight of this infection as a possible cause of idiopathic infertility in males with any known cause of conception failure.

Serum Anti-HPV Antibody Titer as a Marker of Vaccine Effectiveness in Males with Genital Infection.

Introduction: Persistent human papillomavirus (HPV) semen infection is increasingly associated with male infertility. Adjuvant HPV vaccination is suggested to reduce the time to clearance and the disease relapse in males with persistent HPV semen infection. However, only a sub-population of patients show a clinical benefit from adjuvant vaccination. Here, we aimed to address the effectiveness rate of HPV adjuvant vaccination in males with genital tract infection and the possible prognostic markers of healing. Methods: Clinical records from 379 patients with persistent seminal HPV detection, all receiving HPV adjuvant vaccination, were considered. Clinical data, including genital HPV-DNA assessment by INNO-LiPA genotyping, semen HPV-DNA analysis by FISH analysis and serum antibody titer, were collected at basal (T0) and after 6 months (T1) since the vaccination cycle ended. Results: Clearance of genital HPV-DNA was recorded in 326 (86%) patients. Serum HPV-antibody titer at T1 was the most important prognostic factor associated with HPV-DNA clearance. A serum antibody titer equal to or greater than the threshold value 1:125, obtained by ROC curve analysis, was prognostic of healing. Conclusions: Anti-HPV antibody represents a suitable marker of adequate immune response to HPV vaccination in patients with genital infection.

Role of Viral Infections in Testicular Cancer Etiology: Evidence From a Systematic Review and Meta-Analysis.

The most represented histotype of testicular cancer is the testicular germ-cell tumor (TGCT), both seminoma and non-seminoma. The pathogenesis of this cancer is poorly known. A possible causal relationship between viral infections and TGCTs was firstly evoked almost 40 years ago and is still a subject of debate. In the recent past, different authors have argued about a possible role of specific viruses in the development of TGCTs including human papillomavirus (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Parvovirus B-19, and human immunodeficiency virus (HIV). The aim of this present review was to summarize, for each virus considered, the available evidence on the impact of viral infections on the risk of developing TGCTs. The review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all observational studies reported in English evaluating the correlations between viral infections (HPV, CMV, EBV, Parvovirus B19, and HIV) and TGCTs. The methodological quality of studies included in the meta-analysis was evaluated using a modified version of the "Newcastle-Ottawa Scale." Meta-analyses were conducted using the "Generic inverse variance" method, where a pooled odds ratio (OR) was determined from the natural logarithm (LN) of the studies' individual OR [LN (OR)] and the 95% CI. A total of 20 studies (on 265,057 patients) were included in the review. Meta-analysis showed an association with TGCTs only for some of the explored viruses. In particular, no association was found for HPV, CMV, and Parvovirus B-19 infection (p = ns). Conversely, EBV and HIV infections were significantly associated with higher risk of developing TGCTs (OR 7.38, 95% CI 1.89-28.75, p = 0.004; OR 1.71, 95% CI 1.51-1.93, p < 0.00001). In conclusion, we found adequate evidence supporting an oncogenic effect of HIV and EBV on the human testis. Conversely, available data on HPV and TGCTs risk are conflicting and further studies are needed to draw firm conclusions. Finally, current evidence does not support an effect of CMV and Parvovirus B-19 on testicular carcinogenesis.