Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host

Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

Management of HIV-2 resistance to antiretroviral therapy in a HIV-1/HIV-2/HBV co-infected patient

Background The current standard of care is to start antiretroviral therapy in all patients diagnosed with HIV-1, as for HIV-2 current DHHS guideline suggests ART for HIV-2 as soon as diagnosis is established, although this practice is not universal, for instance, in Portugal there are specific criteria to start treatment. Case presentation We present a case of a man, chronically infected with HIV-1, HIV-2 and hepatitis B virus who developed resistance to HIV-2 while maintaining HIV-1 under control. 6 years after starting antiretroviral therapy he had his first virologic failure. We performed HIV-2 resistance tests that revealed high-grade resistance to all nucleoside reverse-transcriptase inhibitors except tenofovir and to all protease inhibitors except darunavir. After a decade of permanent poor adherence to therapy he developed resistance to both tenofovir and darunavir. We put together a new regiment with tenofovir alafenamide + emtricitabine + dolutegravir + maraviroc and nowadays he is with undetectable HIV-1 and HIV-2 viral loads. Conclusions This shows the importance of having access to HIV-2 viral load determination and HIV-2 resistance testing.

Mechanical ventilation affects respiratory microbiome of COVID-19 patients and its interactions with the host

Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper (n=58) and lower (n=35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomic analysis of the lower respiratory tract of ventilated COVID-19 patients identified increased oral microbiota compared to controls. These oral microbiota were found physically associated with proinflammatory immune cells, which showed higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

Association between Vaginal Infections and the Types and Viral Loads of Human Papillomavirus: A Clinical Study Based on 4,449 Cases of Gynecologic Outpatients

Objective. We here evaluated the association between human papillomavirus (HPV) infection and vaginal infections, including bacterial vaginosis (BV), trichomonas vaginalis (TV), and vulvovaginal candidiasis (VVC). Methods. A total of 4,449 women were enrolled in this study and given gynecological examinations. HPV genotyping and viral load determination were performed using a real-time PCR. Vaginal infections were diagnosed using wet mounts of vaginal secretions, gram-stained vaginal secretion smears, and chemical enzyme kits. Results. In this study, the overall HPV-positive rate was 25.06%, and vaginal infection tended to occur in women with HPV infection (P<0.05). HPV infection tended to occur in BV- and TV-positive women (P<0.05) and not in women with microecological disorders, intermediate type BV, VVC, or coinfection (P>0.05). The most common genotypes were HPV58 and HPV53 in women with normal vaginal microecology and HPV16 and HPV52 in the women suffering from vaginal infection. The viral loads among groups for HPV16 and HPV52 showed no statistically significant differences (P=0.940; P=0.167). Conclusions. Our study revealed that BV and TV are associated with HPV infection, especially high-risk HPV infection, while VVC has no association with HPV infection. Further studies are needed to explore the detailed mechanism.