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Background: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations., Methods: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses., Findings: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8-5.1) per 100 person-years to 103.9 (95% CI 103.2-104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3-1.9) to 14.3 (95% CI 14.1-14.6)), abdominal pain (from 0.3 (95% CI 0.1-0.5) to 9.9 (95% CI 9.7-10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4-0.9) to 13.3 (95% CI 13.1-13.6)), cough (from 0.3 (95% CI 0.2-0.5) to 9.1 (95% CI 8.9-9.3)), and anxiety (from 0.8 (95% CI 0.6-1.2) to 11.4 (95% CI 11.2-11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008-0.2) to 1.7 (95% CI 1.6-1.8)), pins and needles (from 0.05 (95% CI 0.03-0.0.9) to 1.5 (95% CI 1.4-1.6)), memory issues (from 0.03 (95% CI 0.02-0.06) to 0.8 (95% CI 0.7-0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004-0.01) to 0.6 (95% CI 0.4-0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03-0.04) to 0.7 (95% CI 0.6-0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1-2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7-3.9); anxiety, 2.3 (1.4-3.8); allergy, 2.1 (1.7-2.8) and sleep disorders, 2.1 (1.5-2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3-2.8)., Interpretation: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets., Funding: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC)., Competing Interests: D.P.A.‘s department has received grant/s from Amgen, Chiesi–Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department. R.P. reports serving on advisory boards for Gilead Sciences, Inc, Pfizer, Inc, Roche Therapeutics, MSD, GSK, ViiV Healthcare, Eli Lilly and Company, PharmaMar, and Atea Pharmaceuticals, Inc; and receiving research grants paid to his institution from MSD, ViiV Healthcare, Gilead Sciences, and PharmaMar. L.M. reports receiving grants from Grifols; receiving honoraria as a speaker from AstraZeneca, Gilead Sciences, GSK, and Pfizer; and participation in advisory boards for Gilead Sciences and Merck. M.M. works for a research group that in the past 3 years received unconditional research grants from Chiesi, UCB, Amgen, Johnson & Johnson, Innovative Medicines Initiative and the European Medicines Agency. D.Ded., Z.C. and J.O. are employees of the Medicines and Healthcare Products Regulatory Agency, which provides the CPRD research service. K.K. is a consortial author in the US National Institutes of Health National COVID Cohort Collaborative (funding expired in 2022 with no renewal or active impact on any current work). G.M. reports receiving consulting fees from Pfizer. A.N. reports grants or contracts from Alfred P. Sloan Foundation, National Institutes of Health and the U.S. Food and Drug Administration. L.P. was supported by a Sara Borrell fellowship awarded by the Spanish Institute of Health Carlos III (CD23/00223). K.L.G is funded through an MRC scholarship with Bayer AG as an industrial partner. All other co-authors declare no competing interests., (© 2024 The Authors.)

This is an observational, cross-sectional, comparative case-control, pilot study aimed at assessing the impact of HIV infection and age on immunological markers in people with HIV (PWH) on antiretroviral therapy (ART). The study included 40 PWH on ART, divided into two age groups (40-45 years vs. ≥60 years), and 30 HIV-uninfected controls matched by sex and age. The results show that older PWH on ART had more comorbidities and a higher frequency of CD8 T cells compared to older controls, with a significant decrease in CD8 naïve T cells with age. Additionally, younger PWH on ART exhibited higher frequencies of activated CD8 T cells and elevated levels of inflammatory markers (sCD14, IL-6) compared to age-matched controls, with values similar to those of older PWH on ART. These findings suggest that younger PWH on ART may experience accelerated immunoaging, highlighting the need for early interventions in this population.

Objectives: The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints., Methods: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles., Results: Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35-51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve., Discussion: Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Disseminated tuberculosis is frequently associated with delayed diagnosis and a poorer prognosis., Objectives: To describe case series of disseminated TB and diagnosis delay in a low TB burden country during the COVID-19 period., Methodology: We consecutively included all patients with of disseminated TB reported from 2019 to 2021 in the reference hospital of the Northern Crown of the Metropolitan Area of Barcelona. We collected socio-demographic information, clinical, laboratory and radiological findings., Results: We included all 30 patients reported during the study period-5, 9, and 16 in 2019, 2020, and 2021 respectively-20 (66.7%) of whom were male and whose mean age was 41 years. Twenty-five (83.3%) were of non-EU origin. The most frequent system involvement was central nervous system ( N  = 8; 26.7%) followed by visceral ( N  = 7; 23.3%), gastro-intestinal ( N  = 6, 20.0%), musculoskeletal ( N  = 5; 16.7%), and pulmonary ( N  = 4; 13.3%). Hypoalbuminemia and anemia were highly prevalent (72 and 77%). The median of diagnostic delay was 6.5 months (IQR 1.8-30), which was higher among women (36.0 vs. 3.5 months; p  = 0.002). Central nervous system involvement and pulmonary involvement were associated with diagnostic delay among women. We recorded 24 cured patients, two deaths, three patients with post-treatment sequelae, and one lost-to-follow up. We observed a clustering effect of patients in low-income neighborhoods ( p  < 0.001)., Conclusion: There was a substantial delay in the diagnosis of disseminated TB in our study region, which might impacted the prognosis with women affected more negatively. Our results suggest that an increase in the occurrence of disseminated TB set in motion by diagnosis delay may have been a secondary effect of the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roure, Vallès, Sopena, Benítez, Reynaga, Bracke, Loste, Mateu, Antuori, Baena, Portela, Llussà, Flamarich, Soldevila, Tenesa, Pérez, Plasencia, Bechini, Pedro-Botet, Clotet and Vilaplana.)

Background: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings., Methods: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both., Results: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life., Conclusions: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction., (© 2022. The Author(s).)

Background: Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression., Methods: We performed a prospective cohort study to identify people living with HIV with advanced kidney disease according to the Kidney Disease Improving Global Outcomes criteria and to assess disease progression over a 48-week period following the offer of targeted multidisciplinary management., Results: From our cohort of 3090 individuals, 55 (1.8%, 95% confidence interval [CI] 1.31-2.25) fulfilled the inclusion criteria. Most were male (83.6%), and the median (interquartile range [IQR]) age was 58 (53.25-66.75) years. Nadir CD4 T-cell count was 135.5 (IQR 43.5-262.75) cells/μl, current CD4 T-cell count was 574 (IQR 438.5-816) cells/μl, and 96% had maintained HIV viral suppression. The most frequent comorbidity was arterial hypertension (85.5%). Inadequate antiretroviral dose was detected in three individuals (5.5%), and drug-drug interactions were recorded in eight (14.5%), mainly involving the use of cobicistat (n = 5 [9%]). Four individuals (7%) required modification of their concomitant treatment. Seven (13%) had to start or resume follow-up with a nephrologist. Nine participants (16.4%) experienced an improvement in kidney disease stage, three individuals (5.5%) underwent renal transplantation, and one (2%) started haemodialysis., Conclusions: Our results show that a multidisciplinary approach, including a critical review of treatment and evaluation of specific requirements, could be useful for anticipating drug-drug interactions and toxicities and for reducing death and hospitalization in people living with HIV with advanced kidney disease., (© 2022 British HIV Association.)

In an ongoing Mediterranean cohort, we compared age-related conditions between 208 HIV-infected persons and 104 matched controls. ≥3 comorbidities were found in 31.0% of HIV-infected patients and 8.7% of controls. Conditions significantly more frequent among the HIV-infected population were: lipid abnormalities, cancer, osteopenia/osteoporosis, liver disease, sexual dysfunction, hearing deficit, sleep disorders, falls, cognitive complaints, being single, living alone, and being elderly at risk. HIV-infected patients aged >70 years had a significantly higher number of cardiovascular risk factors (CVRF) and comorbidities than controls. HIV-infected persons who had never smoked had a higher prevalence of CVRFs, ≥3 comorbidities, liver disease, cancer, and cognitive complaints compared to controls. Factors associated with frailty were being a man who has sex with men, ≥3 CVRFs, nadir CD470 years. The multidisciplinary assessment also revealed concerning findings in social, cognitive, and functional variables among HIV-infected individuals, with a higher prevalence of elderly at risk than among controls.

Background: HIV infection is an increasingly complex chronic disease associated with numerous medical, psychological, and social problems. The life expectancy of affected patients has increased considerably. Medical apps could also play a role in prevention and management of comorbid conditions in the HIV-infected population. Objectives: To determine the usefulness of an app designed specifically for HIV-infected patients aged 60 years or older and to assess changes in patient satisfaction, adherence to treatment, and quality of health care. Methods: A randomized clinical trial was conducted, including 100 patients (50 per group): (1) an experimental group comprising patients using the app + routine medical care (app group) and (2) with routine medical care (control group). The usability of the app and patient satisfaction were evaluated in the app group at week 48. Quality of life, adherence to treatment, and clinical parameters were compared between both groups at 48 weeks, as well as the number of face-to-face visits. Results: We found that 52.2% and 73.8% of patients in the app group used the app at weeks 24 and 48, respectively. Patients used the app for a mean of 23.7 (±2.84) days over the 48 weeks. The most visited screens were health counseling and medical records (24.8% and 22.2%, respectively). At week 48, 85.2% of patients thought that the app was useful and 91.4% would recommend the app to friends or relatives. The app was well valued by participants (4.79 [±0.21] of 5.00) and 64.6% thought that the app improved their health care.

Aims: To determine the prevalence of potential prescribing issues (PPI) in HIV-infected subjects aged ≥65 years according to the Beers and STOPP/START criteria and antiretroviral drug-drug interactions (Liverpool website). Secondary objectives were to assess the concordance between Beers and STOPP/START criteria in our population, and to identify the drugs most frequently involved in PPI., Methods: Cross-sectional cohort study based on a systematic review of the electronic drug prescriptions confirmed by an interview of 91 HIV-infected patients aged ≥65 years. Discrepancies between prescription criteria were assessed using crosstabs and compared using the χ 2 test or Fisher exact test., Results: The mean age was 72.1 (5.6) years, 75.8% had ≥3 comorbidities and 59.3% polypharmacy. PPI were identified in 87.9%: 71.4% by STOPP/START and 45.1% by Beers. Comparing both criteria, 56.9% of PPI by STOPP/START were detected by Beers, while 92.5% of those detected by the Beers criteria were detected by STOPP/START (P < .001). Amber/red flag interactions between antiretrovirals and comedications were found in 45.1%: 3 severe (red) in 2 patients (2.2%). The most frequent drugs involved in PPI were benzodiazepines (>30%). Cobicistat was the drug most frequently involved in potential interactions (42.2%)., Conclusion: The prevalence of PPI among older HIV-infected persons gives cause for concern, as it is almost 90%. Optimization strategies, including a critical review of the treatment plan, should be implemented in clinical routine by a multidisciplinary team, in particular in patients with multiple comorbidities and polypharmacy. The STOPP/START criteria seem to detect more PPI, mainly for European populations., (© 2020 The British Pharmacological Society.)

Objective: Optimization of antiretroviral therapy and anti-inflammatory treatments, such as statins, are among the strategies aimed at reducing metabolic disorders, inflammation and immune activation in people living with HIV (PLWH). We evaluated the potential benefit of combining both strategies., Design: Forty-two PLWH aged ≥40 years receiving a protease inhibitor (PI)-based regimen were randomized (1:1) to switch from PI to Raltegravir (n = 20), or to remain on PI (n = 22). After 24 weeks, all patients received atorvastatin 20mg/day for 48 weeks., Methods: We analyzed plasma inflammatory as well as T-cell maturation, activation, exhaustion and senescence markers at baseline, 24 and 72 weeks., Results: Plasma inflammatory markers remained unchanged. Furthermore, no major changes on T-cell maturation subsets, immunoactivation, exhaustion or immunosenescence markers in both CD4 and CD8 T cell compartments were observed. Only a modest decrease in the frequency of CD38+ CD8 T cells and an increase in the frequency of CD28-CD57+ in both CD4 and CD8 T-cell compartments were noticed in the Raltegravir-switched group., Conclusions: The study combined antiretroviral switch to Raltegravir and Statin-based anti-inflammatory strategies to reduce inflammation and chronic immune activation in PLWH. Although this combination was safe and well tolerated, it had minimal impact on inflammatory and immunological markers., Clinical Trials Registration: NCT02577042., Competing Interests: Unrelated to this work, JB is CEo founder and shareholder of AlbaJuna Therapeutics, S.L. This study was funded by Merk Sharp & Dome (MSD) through the MSD Investigator Studies Program (IIS # 52754), grant to EN. This funder did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript "This does not alter our adherence to PLOS ONE policies on sharing data and materials.