The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to m ark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total H IV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART.

Introduction Some patients with COVID-19 pneumonia present systemic disease involving multiple systems. There is limited information about the clinical characteristics and events leading to acute kidney injury (AKI). We described the factors associated with the development of AKI and explored the relation of AKI and mortality in Mexican population with severe COVID-19. Methods We retrospectively reviewed the medical records of individuals with severe pneumonia caused by SARS-CoV-2 hospitalized at the largest third-level reference institution for COVID-19 care in Mexico between March and April 2020. Demographic information, comorbidities, clinical and laboratory data, dates of invasive mechanical ventilation (IMV) and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded. Results Of 99 patients studied, 58 developed AKI (58.6%). The risk factors for AKI were older age (OR = 1.07, 95% CI = 1.01–1.13, p = 0.024); obesity (OR = 6.58, 95% CI = 1.8–24.05, p = 0.040); and the need for IMV (OR = 6.18, CI = 1.29–29.58, p = 0.023). The risk factors for mortality were obesity (OR = 5.57, 95% CI = 1.48–20.93, p = 0.011); requirement of vasoactive drugs on admission (OR = 5.35, 95% CI = 1.16–24.61, p = 0.031); and AKI (OR = 8.61, 95% CI = 2.24–33.1, p = 0.002). In-hospital mortality was significantly higher in patients with AKI stage 3 (79.3%) and AKI stage 2 (68.7%) compared with those with AKI stage 1 (25%; p = 0.004). Fifty-three patients underwent the furosemide stress test (FST) to predict progression to AKI stage 3. Of those, 12 progressed to AKI stage 3 (22%). The ROC curve for the FST had an AUC of 0.681 (p = 0.009); a sensitivity of 81.6% and a specificity of 54.5%. Conclusions AKI was common in our cohort of patients with severe pneumonia caused by SARS-CoV-2 infection. The risk factors for AKI were older age, obesity and the need for of IMV on admission. The risk factors for mortality were obesity, requirement of vasoactive drugs on admission and AKI. Mortality was more frequent in patients with AKI stages 2–3. The FST had an acceptable predictive capacity to identify patients progressing to AKI stage 3.

The total population was 72% male and 28% female, median age was 58 years; minimal follow-up was 9 months (mean = 51, median = 34). Cochleostomy was performed in eight cases and round window insertion was performed in 19 (two patients were removed from each group in the analysis due to their bilateral implantation under a different approach). The mean time from implant to vestibular symptoms was 53 months, median = 32; a Kaplan Meier graphic showed the round window approach has faster onset of symptoms with statistical significance (p = 0.020). The most common complaint was instability in all patients and after both surgical approaches. No difference in symptoms was found with a Kruskall Wallis test except for vertigo spells (more common in the round window approach). In 12 patients the symptomatology was attributed to the implanted side. In the long-term follow-up a relatively high number of patients (20/25) recovered with standard treatment, suggesting the presence of the implant is not associated with poor recovery prognosis.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28–44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99–52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04–53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Understanding the complexity of the long-lived HIV reservoir during antiretroviral therapy (ART) remains a considerable impediment in research towards a cure for HIV. To address this, we developed a single-cell strategy to precisely define the unperturbed peripheral blood HIV-infected memory CD4+ T cell reservoir from ART-treated people living with HIV (ART-PLWH) via the presence of integrated accessible proviral DNA in concert with epigenetic and cell surface protein profiling. We identified profound reservoir heterogeneity within and between ART-PLWH, characterized by new and known surface markers within total and individual memory CD4+ T cell subsets. We further uncovered new epigenetic profiles and transcription factor motifs enriched in HIV-infected cells that suggest infected cells with accessible provirus, irrespective of reservoir distribution, are poised for reactivation during ART treatment. Together, our findings reveal the extensive inter- and intrapersonal cellular heterogeneity of the HIV reservoir, and establish an initial multiomic atlas to develop targeted reservoir elimination strategies.