Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection. ' 2005 Wiley-Liss, Inc.Key words: HPV infection; HPV persistence; Chlamydia trachomatis; epidemiology Persistent oncogenic HPV infection is recognized as a necessary factor in development of high grade cervical intraepithelial neoplasia and invasive cervical cancer. 1 Genital infections with oncogenic HPV types are very common among sexually active women, but only a minority of infected women will have a persistent HPV infection. 2-4 Type-specific persistence of HPV (defined as repeated detectability of the same type of HPV DNA in serial samples) is a much stronger risk factor for high-grade CIN 5 and cervical cancer 6 than HPV infection per se.Chlamydia (C.) trachomatis has been found repeatedly to associate with cervical neoplasia and invasive cancer in cross-sectional case-control studies, 7,8 although the association has commonly been thought to be the result of confounding by HPV. During recent years, an association with C. trachomatis has also been found in several biobank-based longitudinal studies with invasive cervical cancer as endpoint. [9][10][11][12] The vexed question of whether the association could be due to confounding by HPV infection is, however, only possible to address in cohort studies comprising only HPV-infected women.A possible explanation for the association of C. trachomatis and cervical cancer might be that the C. trachomatis-induced inflammation results in an impaired ability to clear HPV infections.To investigate these issues, we carried out a prospective, population-based cohort study restricted to HPV-infected women with HPV persistence as the endpoint. Subjects and methods Study settingA population-based randomized mul...

Background Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. Objective To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. Designs, settings, and participants A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. Intervention In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. Outcome measurements The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. Results and limitations Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of 4 d of enzalutamide on virus replication ( p = 0.084). The epidemiological study has limitations that include residual confounders. Conclusions The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. Patient summary We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.

Key Points Question Are cerebrospinal fluid (CSF) SARS-CoV-2 antigens associated with central nervous system inflammation in patients with COVID-19? Findings Of 44 patients with COVID-19 (23 neurosymptomatic) included in this hospital-based cross-sectional study, CSF nucleocapsid antigen was detectable in 89% of patients with available data and was significantly correlated with immune activation markers (neopterin and interferon γ). Moreover, neurosymptomatic patients had a more pronounced inflammatory CSF profile compared with neuroasymptomatic patients that could not be attributed to differences in COVID-19 severity. Meaning These results suggest that viral components may contribute to central nervous system immune responses without direct viral invasion and highlight the clinical importance of neurologic symptoms.