Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 ...in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19.
In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period.
Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% 95% CI 3·82–4·27) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 3·04% of 4672; risk ratio RR 1·33 95% CI 1·12–1·58; p<0·001). Seroprevalence was higher in male health-care workers (331 5·45% of 6077) than in female health-care workers (832 3·66% of 22 715; RR 1·49 1·31–1·68; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 4·55% of 16 356) than health-care workers in other settings (384 3·29% of 11 657; RR 1·38 1·22–1·56; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 7·19% of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 4·35% of 15 983; RR 1·65 1·34–2·03; p<0·001). 622 53·5% of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 32·39% of 1164 participants with this symptom were seropositive vs 786 2·84% of 27 628 without this symptom; RR 11·38 10·22–12·68). The study is registered at ClinicalTrials.gov, NCT04346186.
The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19.
Lundbeck Foundation.
Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic ...risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1-3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4
T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in
, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.
Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de ...novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 1.08-2.28 per decade older), being underweight (RR: 5.79 1.70-19.71), current smoking (RR: 2.34 1.06-5.16), diabetes (RR: 3.89 1.72-8.80) and protease inhibitor use (RR: 2.45 1.27-4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.
Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte ...count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors.
Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes.
We included 871 PLWH and 4355 uninfected controls. PLWH had - 0.021 - 0.031 - 0.011 × 10
/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with - 0.035 - 0.045, - 0.025 × 10
/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 325, 851 ng/ml, and 194 57, 330 ng/ml, respectively).
PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls.
Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor ...for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.
In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses.
Exposure to thymidine analogs and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to thymidine analogs and/or ddI 3.7 cm per year (2.3-5.1), but not time since discontinuation -1.1 cm per year (-3.4 to 1.1), was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension adjusted odds ratio (aOR) 1.62 (1.13-2.31), hypercholesterolemia aOR 1.49 (1.06-2.11), and low high-density lipoprotein aOR 1.40 (0.99-1.99).
This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.
Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator ...(TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class-based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways) and immune response like T-cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism.
Apolipoprotein E (apoE) plays a crucial role in cholesterol metabolism, and high levels of apoE in plasma are associated with cardiovascular disease and all-cause mortality. We aimed to assess if HIV ...is independently associated with high plasma apoE and to determine HIV-related risk factors for high plasma apoE.
We included 661 people with HIV (PWH) from the Copenhagen Comorbidity in HIV (COCOMO) study with available measurement of plasma apoE. COCOMO participants were frequency matched 1:1 on age and sex with controls from the Copenhagen General Population Study. High plasma apoE was defined as levels above the 90th percentile (66.2 mg/L). The association between HIV and high plasma apoE was assessed using logistic regression models. Among PWH, both linear and logistic regression models were used to determine HIV-specific risk factors for high plasma apoE.
Mean age was 52 years and 89 % were male. Median plasma apoE was 49.0 mg/L in PWH and 43.3 mg/L in controls, p < 0.001. HIV was associated with higher plasma apoE after adjusting for potential confounders, including triglycerides (odds ratio 2.14 95 % CI: 1.39–3.29, p < 0.001). In PWH, higher plasma apoE was associated with a previous AIDS-defining condition in linear models before adjustment for triglycerides and integrase strand transfer inhibitor use in fully adjusted linear models.
PWH had higher plasma apoE than controls even after adjusting for triglycerides. Further studies are needed to elucidate the clinical impact of high plasma apoE in PWH.
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•People with HIV had higher plasma apoE levels than controls from the general population.•Plasma apoE was consistently higher in people with HIV when stratifying by triglyceride levels.•People with HIV also had higher apoE/apoB ratio compared to controls.•Thus, the association between HIV status and apoE was independent of changes in other lipid parameters.
This study aimed to investigate the incidence of enterococcal infections and determine risk factors associated with enterococcal bloodstream infection (BSI) within the first year post-liver ...transplantation (LTx). We included 321 adult liver transplant recipients transplanted from 2011 to 2019 in a prospective cohort study. Cumulative incidence of enterococcal infections and risk factors associated with BSI were investigated in a competing risk model and time-updated Cox models, respectively. A total of 223 enterococcal infections were identified in 89 recipients. The cumulative incidences of first enterococcal infection and first enterococcal BSI were 28% (95% CI (23–33)) and 11% (CI (7–14)), respectively. Risk factors associated with enterococcal BSI were previous infections in the biliary tract (HR, 33; CI (15–74); p < 0.001), peritoneum (HR, 8.1; CI (3–23); p < 0.001) or surgical site (HR, 5.5; CI (1.4–22); p = 0.02), recipient age (HR per 10 years increase, 1.2; CI (1.03–1.6); p = 0.03), and cold ischemia time (HR per one hour increase, 1.2; CI (1.1–1.3); p < 0.01). Enterococcal infections are highly prevalent the first year post-LTx, and recipients with enterococcal infections in the biliary tract, peritoneum, or surgical site are at increased risk of BSI. These findings may have implications for the choice of empiric antibiotics early post-LTx.
Abstract
Background
Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 IL-6, ...interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 sCD14 and soluble CD163 sCD163) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.
Methods
We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.
Results
PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL 95% confidence interval, −308 to −116 mL), lower forced vital capacity (−208 mL −322 to −93 mL), and airflow limitation (aOR, 2.62 1.58–4.36) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).
Conclusion
IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
Interleukin 6 concentrations were significantly higher in well-treated people with human immunodeficiency virus (HIV) (PWH) than in uninfected controls. Such elevations were independently associated with lower dynamic lung function and airflow limitation in well-treated PWH with undetectable viral replication.
Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, ...and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH).
From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis.
In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A , TET2 , and ASXL1 , accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1β, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses.
In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.
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