Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.

Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+ T cell functions, which requires a deeper understanding of CD8+ T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+ T cells and proteomic analysis of purified CD8+ T cell subsets identified TOXhiTCF1+CD39+CD8+ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+ T cells were found at higher frequency than TCF1-CD39+CD8+ T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+ cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+ T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+ T cells contributes to limiting SIV and HIV persistence.

Profound phenotypic and epigenetic heterogeneity of the HIV-1-infected CD4+ T cell reservoir.

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.

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

The time between Palaeolithic hearths.

Resolving the timescale of human activity in the Palaeolithic Age is one of the most challenging problems in prehistoric archaeology. The duration and frequency of hunter-gatherer camps reflect key aspects of social life and human-environment interactions. However, the time dimension of Palaeolithic contexts is generally inaccurately reconstructed because of the limitations of dating techniques1, the impact of disturbing agents on sedimentary deposits2 and the palimpsest effect3,4. Here we report high-resolution time differences between six Middle Palaeolithic hearths from El Salt Unit X (Spain) obtained through archaeomagnetic and archaeostratigraphic analyses. The set of hearths covers at least around 200-240 years with 99% probability, having decade- and century-long intervals between the different hearths. Our results provide a quantitative estimate of the time framework for the human occupation events included in the studied sequence. This is a step forward in Palaeolithic archaeology, a discipline in which human behaviour is usually approached from a temporal scale typical of geological processes, whereas significant change may happen at the smaller scales of human generations. Here we reach a timescale close to a human lifespan.

The gray zone between legitimate and predatory open access scientific publishing.

Certain open access publishers based on the article processing charges model have found it highly profitable to operate within a gray zone that encompasses both legitimate and predatory publishing practices. In this context, maximum profits can be obtained by adequate combinations of journal acceptance rates and elevated article processing charges. Considering that the gray zone can be particularly challenging to identify and that it poses risks for authors aiming to establish academic carreers, we believe it is important to provide a comprehensive description of it.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

GPCRmd uncovers the dynamics of the 3D-GPCRome.

G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.

Publisher Correction: GPCRmd uncovers the dynamics of the 3D-GPCRome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Phylodynamics of HIV in the Mexico City Metropolitan Region.

Evolutionary analyses of viral sequences can provide insights into transmission dynamics, which in turn can optimize prevention interventions. Here, we characterized the dynamics of HIV transmission within the Mexico City metropolitan area. HIV pol sequences from persons recently diagnosed at the largest HIV clinic in Mexico City (between 2016 and 2021) were annotated with demographic/geographic metadata. A multistep phylogenetic approach was applied to identify putative transmission clades. A data set of publicly available sequences was used to assess international introductions. Clades were analyzed with a discrete phylogeographic model to evaluate the timing and intensity of HIV introductions and transmission dynamics among municipalities in the region. A total of 6,802 sequences across 96 municipalities (5,192 from Mexico City and 1,610 from the neighboring State of Mexico) were included (93.6% cisgender men, 5.0% cisgender women, and 1.3% transgender women); 3,971 of these sequences formed 1,206 clusters, involving 78 municipalities, including 89 clusters of ≥10 sequences. Discrete phylogeographic analysis revealed (i) 1,032 viral introductions into the region, over one-half of which were from the United States, and (ii) 354 migration events between municipalities with high support (adjusted Bayes factor of ≥3). The most frequent viral migrations occurred between northern municipalities within Mexico City, i.e., Cuauhtémoc to Iztapalapa (5.2% of events), Iztapalapa to Gustavo A. Madero (5.4%), and Gustavo A. Madero to Cuauhtémoc (6.5%). Our analysis illustrates the complexity of HIV transmission within the Mexico City metropolitan area but also identifies a spatially active transmission area involving a few municipalities in the north of the city, where targeted interventions could have a more pronounced effect on the entire regional epidemic. IMPORTANCE Phylogeographic investigation of the Mexico City HIV epidemic illustrates the complexity of HIV transmission in the region. An active transmission area involving a few municipalities in the north of the city, with transmission links throughout the region, is identified and could be a location where targeted interventions could have a more pronounced effect on the entire regional epidemic, compared with those dispersed in other manners.

The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection.

BACKGROUND: Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. RESULTS: We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. CONCLUSION: We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.

Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. METHODS: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. RESULTS: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. CONCLUSIONS: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

SARSCoV-2 antibody prevalence and titers in persons living with HIV cared for at a large tertiary reference center in Mexico City.

OBJECTIVE: To assess SARS-CoV-2 antibody prevalence and titers in people living with HIV (PLWHIV) on antiretroviral treatment (ART) enrolled at a tertiary reference hospital in Mexico. METHODS: Two plasma aliquots per person, used for HIV viral load follow-up between 01/2020 and 09/2021, were used to assess total anti-N and neutralizing SARS-CoV-2 antibodies. Sociodemographic, clinical, and SARS-CoV-2 exposure risk information were collected. The risk associated with SARS-CoV-2 exposure and associations with antibody titers were analyzed with logistic, Cox, and linear multivariable models. RESULTS: 803 PLWHIV participated; 233 had detectable SARS-CoV-2 antibodies (prevalent cases), and 132 seroconverted (incident cases). Overall, the adjusted prevalence was 46.45%, with an incidence rate of 3.78 cases/100 person-months. Factors associated with prevalent cases included lower age, location (western zone of Mexico City and the neighboring Mexico State), use of public transport, attendance at meetings without social distancing, and higher CD4 + T cell counts (p < 0.05; multivariable logistic model). BNT162b2 vaccination reduced incident cases (Cox adjusted HR = 0.4; p = 0.013). Notably, previously infected and vaccinated individuals showed maximization of neutralizing activity (p < 0.001). No associations between SARS-CoV-2 neutralization and HIV-related variables (CD4 + T cell counts, viral load, number of years in viral suppression, ART regimen) were found in multivariable analysis. CONCLUSIONS: SARS-CoV-2 infection was associated with community risk rather than HIV-associated variables in PLWH on ART and clinical follow-up. Antibody neutralization activity in vaccinated participants was maximized with previous SARS-CoV-2 infection.

Mental health and adherence to antiretroviral therapy among Mexican people living with HIV during the COVID-19 pandemic.

BACKGROUND: The mental health and medical follow-up of people living with HIV (PLWH) have been disrupted by the COVID-19 pandemic. The objectives of this study were to assess anxiety, depression and substance use in Mexican PLWH during the pandemic; to explore the association of these symptoms with adherence to antiretroviral therapy (ART), and to compare patients with and without vulnerability factors (low socioeconomic level, previous psychological and/or psychiatric treatment). METHODS: We studied 1259 participants in a cross-sectional study, PLWH receiving care at the HIV clinic in Mexico City were contacted by telephone and invited to participate in the study. We included PLWH were receiving ART; answered a structured interview on sociodemographic data and adherence to ART; and completed the psychological instruments to assess depressive and anxiety symptoms and substance use risk. Data collection was performed from June 2020 to October 2021. RESULTS: 84.7% were men, 8% had inadequate ART adherence, 11% had moderate-severe symptoms of depression, and 13% had moderate-severe symptoms of anxiety. Adherence was related to psychological symptoms (p < 0.001). Vulnerable patients were more likely to be women, with low educational level and unemployed (p < 0.001). CONCLUSIONS: It is important to address mental health of PLWH during the COVID-19 pandemic, with special attention to the most vulnerable individuals. Future studies are needed to understand the relationship between mental health and ART adherence.

Assessing HIV knowledge in Mexican people living with HIV: development and validation of CC-VIH questionnaire.

The level of knowledge that people living with human immunodeficiency virus (HIV) have about their disease can impact their adherence to treatment. The aim of this study was to develop a tool to assess the knowledge about HIV among people receiving treatment at a specialized clinic in Mexico City. To establish content validity, expert judges were invited to conceptualize the tool and propose items for the defined dimensions. A total of 490 individuals living with HIV completed the 91-item questionnaire, with 82.2% being male and a mean age of 36.1 years. We conducted an exploratory factor analysis, resulting in a reduced questionnaire of 45 questions. A three-factor solution explained 36.2% of the variance in HIV knowledge. The total scale had a reliability coefficient of 0.937, and each subscale had reliabilities of 0.828, 0.856 and 0.859. Lower educational level (F(336) = 8.488, p < 0.001) and female gender (t(399) = 2.003, p = 0.046) were associated with lower scores on the HIV knowledge questionnaire. This tool appears suitable for measuring HIV knowledge in people living with HIV, although future studies are required to confirm its structure and reduce its extension.

HIV drug resistance in persons initiating or reinitiating first-line antiretroviral therapy in Paraguay: Results of a National Patient Survey.

Human immunodeficiency virus (HIV) drug resistance increases mortality and morbidity and antiretroviral therapy (ART) costs. We describe Paraguay's first nationally representative survey on pretreatment drug resistance (PDR) conducted among persons who initiated or reinitiated ART in 2019. ​​​​We conducted a cross-sectional survey of antiretroviral (ARV) drug resistance in Paraguay in 2019. Participants were sampled at four comprehensive care clinics where 90% of patients with HIV in Paraguay initiate ART. Patients included were adults ≥18 years old who initiated first-line ART or reinitiated the same first-line ART regimen after ≥3 months of discontinuation. Of 208 patients, 93.8% had no prior ART exposure, 3.8% reinitiated the same regimen, 2.4% had unknown prior ART exposure; and 31.3% had a CD4 count <200 cells/µl. Mutations associated with resistance were present in 15.4% of patients. Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI) were present in 13.0% of patients, nucleoside reverse transcriptase inhibitors in 4.3%, and integrase inhibitors in 3.4%. Mutations associated with resistance to tenofovir were present in 1.0% of patients and emtricitabine/lamivudine in 1.4%. ​​Nearly one in six patients had PDR in Paraguay's first nationally representative sample. High NNRTI PDR prevalence underscores the need to accelerate the transition to dolutegravir-based first-line ART. The low PDR prevalence of tenofovir and emtricitabine is reassuring as these ARVs are part of the World Health Organization (WHO)-recommended oral pre-exposure prophylaxis regimen. The high proportion of individuals initiating ART at a late disease stage highlights the need to improve treatment linkage strategies and implement WHO rapid ART initiation recommendations.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

Clinical Follow-Up in People Living with HIV During the COVID-19 Pandemic in Mexico.

Clinical follow-up in people living with HIV (PLWH) has individual and public health implications. The objectives of this study were to measure variables related to follow-up failures, identify self-reported reasons to maintain adequate follow-up or for having follow-up failures, and know how the pandemic influenced patients' clinical follow-up. Participants were PLWH receiving HIV-health care at a hospital-based clinic in Mexico City which became an exclusive COVID-19 health service. Participants completed a telephone semi-structured interview and online psychological questionnaires. Lower educational and socioeconomic level, longer times of transportation to the clinic, being attended by different doctors, detectable viral load, having previous dropouts, inadequate antiretroviral adherence, and less HIV knowledge were related to follow-up failures. COVID-19 had a significant negative impact, but it also had positive repercussions for patients with adequate follow-up. These results could help develop effective psychosocial programs and improve healthcare in institutions to facilitate patient retention.

RESUMEN: El seguimiento clínico en las personas que viven con VIH (PVV) tiene implicaciones individuales y de salud pública. Los objetivos de este estudio fueron medir las variables relacionadas con las fallas en el seguimiento, identificar las razones reportadas para mantener un seguimiento adecuado o para tener fallas en el seguimiento, y conocer cómo la pandemia influyó en el seguimiento clínico de los individuos. Los participantes eran PVV que recibían atención médica para el VIH en una clínica hospitalaria de Ciudad de México que se convirtió en un servicio exclusivo para COVID-19. Los participantes completaron una entrevista semiestructurada por teléfono y cuestionarios psicológicos en línea. El nivel educativo y socioeconómico más bajo, mayor tiempo de transporte a la clínica, falta de continuidad del médico, carga viral detectable, tener abandonos previos, inadecuada adherencia al tratamiento antirretroviral y menor conocimiento del VIH se relacionaron con las fallas en el seguimiento. La pandemia demostró tener un importante impacto negativo, pero también tuvo repercusiones positivas para los pacientes con un seguimiento adecuado. Estos resultados son importantes para desarrollar programas psicosociales eficaces y mejorar la atención sanitaria en las instituciones para facilitar la retención de los pacientes.

Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease.

BACKGROUND: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. METHODS: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. RESULTS: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. CONCLUSIONS: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

POSTERIOR SEGMENT OCULAR FINDINGS IN CRITICALLY ILL PATIENTS WITH COVID-19.

PURPOSE: To describe ophthalmological fundoscopic findings in patients with COVID-19 admitted to the intensive care unit of the largest third-level referral center for COVID-19 in Mexico City. METHODS: In this cross-sectional single-center study, consecutive patients admitted to the intensive care unit with a diagnosis of COVID-19 underwent fundus examination with an indirect ophthalmoscope. Clinical photographs were taken using a posterior-pole camera. We explored the association between ocular manifestations and demographic characteristics, inflammatory markers, hemodynamic factors, and comorbidities. RESULTS: Of 117 patients examined, 74 were men; the median age was 54 years (range: 45-63 years). Forty-two patients had ophthalmological manifestations (unilateral in 23 and bilateral in 19), and 10 of these patients had more than one ophthalmological manifestation. Ocular findings were papillitis (n = 13), cotton wool spots (n = 12), retinal hemorrhages (n = 5), retinal nerve fiber layer edema (n = 8), macular whitening (n = 5), retinal vascular tortuosity (n = 4), papillophlebitis (n = 3), central retinal vein occlusion (n = 1), and branch retinal vein occlusion (n = 1). Ocular fundus manifestations were not associated with demographic characteristics, inflammatory markers, hemodynamic factors, or comorbidities. CONCLUSION: More than one-third of patients with severe COVID-19 had ophthalmological manifestations. The most frequent fundoscopic findings were optic nerve inflammation, microvasculature occlusion, and major vascular occlusions. We recommend long-term follow-up to prevent permanent ocular sequelae.

Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury.

In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1ß were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.