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Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories.
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COVID-19 , Infección Hospitalaria , Gripe Humana , Unidades de Cuidados Intensivos , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/mortalidad , Gripe Humana/epidemiología , Gripe Humana/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Incidencia , Infección Hospitalaria/epidemiología , Suecia/epidemiología , SARS-CoV-2/aislamiento & purificación , Respiración Artificial , Adulto , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/tratamiento farmacológico , Enfermedad Crítica , Anciano de 80 o más AñosRESUMEN
In May 2024, the Swedish Reference Group on Antiviral Therapy updated the guidelines on management of HIV infection in pregnancy. The most important recommendations and revisions were: (i) ART during pregnancy should be started as early as possible and continue after delivery; (ii) Suppressive ART should normally not be modified; (iii) The treatment target of HIV RNA <20 copies/ml remains; (iv) Dolutegravir/emtricitabine/tenofovir DF is the first-line drug combination also in pregnant women and women planning pregnancy; (v) There is no evidence of an increased risk of neural tube defects associated with dolutegravir; (vi) Mode of delivery for women with effective ART and HIV RNA <200 copies/ml should follow standard obstetric procedures; (vii) Caesarean section is recommended if HIV RNA ≥200 copies/ml; (viii) Scalp electrode, foetal blood sampling and/or vacuum delivery should be used on strict indications, but does not necessitate intensified infant prophylaxis; (ix) Management and mode of delivery in case of premature or full-term rupture of membranes should follow standard obstetric procedures; (x) Recommended infant antiretroviral prophylaxis has been updated; (xi) The duration of infant antiretroviral prophylaxis (gestational age ≥35 weeks and mother on effective ART and HIV RNA <200 copies/ml) has been changed from 4 to 2 weeks; (xii) Infants born to women with HIV RNA ≥200 copies/ml should receive 4 weeks of combination prophylaxis; (xiii) Fertility evaluation and assisted reproduction should be offered to women on suppressive ART according to the same principles as for other women; (xiv) Women living with HIV should still be advised against breastfeeding; (xv) Women who nevertheless opt to breastfeed should be offered intensified support and follow-up.
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Fármacos Anti-VIH , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Humanos , Embarazo , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Fármacos Anti-VIH/uso terapéutico , Suecia , Recién Nacido , Piridonas/uso terapéutico , Emtricitabina/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Piperazinas/uso terapéutico , Tenofovir/uso terapéutico , OxazinasRESUMEN
Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers that included uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of the CSF proteins in HIV-associated dementia ( HAD ) and neurosymptomatic CSF escape ( NSE ). These reveal a complex but coherent picture of CSF protein changes that includes highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of neuroasymptomatic systemic HIV-1 progression, including two common patterns, designated as lymphoid and myeloid patterns, related to the principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, and further the mechanistic understanding of HIV-1-related CNS pathobiology.
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OBJECTIVES: To study intrathecal kappa free light chain (KFLC) synthesis in people living with HIV (PLWH) in comparison with multiple sclerosis (MS). METHODS: Cross-sectional analysis including 56 untreated and 150 well treated PLWH, and compared with 58 controls, and 223 MS patients. RESULTS: Elevated serum/cerebrospinal fluid (CSF) IgG and KFLC indices were observed in untreated PLWH. Seventy percent of untreated PLWH had KFLC index above 6.1, a threshold associated with clinically isolated syndrome/MS diagnosis. No association was found between KFCL index and CSF markers of neuronal injury in either PLWH or MS patients. CONCLUSIONS: HIV-related immune system dysfunction is often associated with an elevated KFLC index akin to those observed in MS. HIV infection should be considered as a differential diagnosis for patients presenting with neurological symptoms and increased intrathecal immunoglobulin synthesis.
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BACKGROUND: Our aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV. METHODS: In this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) ≥ 2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health). RESULTS: Nine percent of the Swedish HIV cohort in 2023 (n = 8531) met at least one criterion for difficult-to-treat HIV. Most of them had ≥ 2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p = 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group. CONCLUSIONS: Although 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Femenino , Fármacos Anti-VIH/uso terapéutico , Estudios Transversales , Suecia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Recuento de Linfocito CD4 , Carga Viral , Terapia Antirretroviral Altamente ActivaRESUMEN
BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.
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COVID-19 , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Sistema Nervioso Central , Astrocitos , Citocinas , BiomarcadoresRESUMEN
Co-infections with invasive candidiasis have been reported to be overrepresented in severe COVID-19. This report presents an unusual case of chronic Candida meningitis following intensive care for COVID-19.
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COVID-19 , Meningitis , Humanos , Candida albicans , GlucanosRESUMEN
OBJECTIVE: To assess Kaposi sarcoma (KS) by HIV-status in Sweden 1983-2017, with particular focus on extracutaneous KS. DESIGN: Population-based study linking the Total Population Registry, the Swedish HIV Registry InfCareHIV, and the Swedish Cancer Registry. METHODS: We included all Swedish residents, born in or outside Sweden between 1940 and 2000 ( n â=â8 587 829), assessing the annual incidence of KS, adjusted hazard ratios (adjHR), and odds ratios (adjOR) in the pre and postcombination antiretroviral therapy (ART) eras. RESULTS: KS was found in 324 individuals of whom 202 (62%) were people with HIV (PWH). While the incidence of KS decreased in PWH, it remained higher compared to HIV-negative at end of follow-up (28 vs. 0.09 per 100 000 person-years, P â<â0.001). In the post-ART era, PWH still had an increased risk of both cutaneous [adjHR 616, 95% confidence interval (CI) 410-926] and extracutaneous KS (adjHR 2068, 95% CI 757-5654), compared to HIV-negative individuals, although there were no cases of extracutaneous disease among virally suppressed PWH. In the post-ART era, the relative risk for KS remained higher in men, particularly men who have sex with men, and viral suppression was associated with lower odds of KS (adjOR 0.05, 95% CI 0.03-0.09). CONCLUSIONS: KS remained increased in PWH in the post-ART era, with a particularly high risk for extracutaneous disease compared to HIV-negative individuals. Notably, there were no cases of extracutaneous disease among virally suppressed PWH, suggesting a less aggressive disease in this population. Further studies on KS in virally suppressed PWH are warranted.
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Infecciones por VIH , Sarcoma de Kaposi , Minorías Sexuales y de Género , Masculino , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/complicaciones , Homosexualidad Masculina , RiesgoRESUMEN
Background: Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. Methods: We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). Results: In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4+ T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or ≥3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4+ T-cell strata after 1 or ≥3 (median, 6.6) years of ART. Conclusions: In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4+ T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.
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BACKGROUND: The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated. METHODS: We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50âcopies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200âcopies/ml or one >1000âcopies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios. RESULTS: In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000âcopies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000âcopies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained. CONCLUSION: High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Carga Viral , Antirretrovirales/uso terapéutico , ARN/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Insuficiencia del TratamientoRESUMEN
Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12â µmol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5â mg, folic acid 0.8â mg and pyridoxine 3.0â mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7â µmol/l (95% confidence interval 14.7-16.7) to 10.3â µmol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5â µmol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter.
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BACKGROUND: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. METHODS: We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. RESULTS: We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. CONCLUSIONS: Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Betametasona/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe , ARN Viral , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Importance: Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF). Objective: To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity. Design, Setting, and Participants: This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, ß2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]). Results: Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r = 0.38; P = .03) and interferon γ (r = 0.42; P = .01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, ß2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P = .03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P = .04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P = .002). No differences were seen in any CSF biomarkers in moderate compared with severe disease. Conclusions and Relevance: In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
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COVID-19 , Adulto , Antígenos Virales , Biomarcadores/líquido cefalorraquídeo , Estudios Transversales , Femenino , Humanos , Interferón gamma , Masculino , Persona de Mediana Edad , Neopterin/líquido cefalorraquídeo , Proteínas de Neurofilamentos , ARN Viral , SARS-CoV-2RESUMEN
BACKGROUND: The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. METHODS: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). RESULTS: We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively). CONCLUSIONS: Cardiac dysfunction occurs commonly in critically ill patients with COVID-19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.
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COVID-19 , Cardiopatías , Disfunción Ventricular Izquierda , Disfunción Ventricular Derecha , COVID-19/complicaciones , Enfermedad Crítica , Cardiopatías/complicaciones , Humanos , Suecia/epidemiologíaRESUMEN
OBJECTIVE: To assess incidence and relative risk of cancer in Sweden, by HIV status, from 1988 to 2017. DESIGN: Population-based register study. METHODS: From the Swedish Total Population Register, all people born between 1940 and 2000 (nâ=â8â587â629), and resident in Sweden sometime 1983-2017 were identified and linked to National HIV Register InfCareHIV, National Cancer Register, and LISA database. We present incidence and adjusted hazard ratios (adjHR) of infection and noninfection-related cancer for three periods between 1988 and 2017. RESULTS: Incidence and relative risk of infection-related cancer decreased but remained higher in people with HIV (PWH) than in HIV-negative. The proportion attributable to infection remained higher in PWH than in HIV-negative (44 vs. 9%). Women with HIV had lower risk of infection-related cancer than men with HIV [adjusted hazard ratio (adjHR) 0.6, 95% CI 0.4-0.9], mainly driven by lower incidence of Kaposi's sarcoma (adjHR 0.1, 95% CI 0.0-0.4). Current viral suppression (adjHR 0.3, 95% CI 0.2-0.5) was associated with lower risk of infection-related cancer. Current CD4+ cell count less than 200âcells/µl was associated with both infection-related (adjHR 15.3, 95% CI 10.7-21.8) and noninfection-related cancer (adjHR 2.5, 95% CI 1.5-4.1), as was CD4+ cell count increases less than 100âcells/µl post antiretroviral therapy (ART) (infection-related cancer adjHR 6.6, 95% CI 4.2-10.6, noninfection-related cancer adjHR 2.0, 95% CI 1.2-3.3). CONCLUSION: Current CD4+ cell count and failure to restore CD4+ cell count both associated with infection and noninfection-related cancer. Viral suppression associated with lower risk of infection-related cancer. Early HIV detection and early adherent ART remain essential for cancer prevention.
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Infecciones por VIH , Neoplasias , Sarcoma de Kaposi , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Neoplasias/complicaciones , Sarcoma de Kaposi/epidemiología , Carga ViralRESUMEN
BACKGROUND: Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD. METHODS: We determined BBB integrity by measuring cerebrospinal fluid (CSF)/plasma albumin ratios in archived CSF samples prior to and after initiation of ART in longitudinally-followed neuroasymptomatic HIV-1-infected individuals and patients with HAD. We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of ß2-micoglobulin, neopterin, and neurofilament light chain protein (NfL). RESULTS: We included 159 HIV-infected participants; 82 neuroasymptomatic individuals and 77 with HAD. All neuroasymptomatic individuals (82/82), and 10/77 individuals with HAD, were longitudinally followed with a median (interquartile range, IQR) follow-up of 758 (230-1752) days for the neuroasymptomatic individuals, and a median (IQR) follow-up of 241 (50-994) days for the individuals with HAD. Twelve percent (10/82) of the neuroasymptomatic individuals and 80% (8/10) of the longitudinally-followed individuals with HAD had elevated albumin ratios at baseline. At the last follow-up, 9% (7/82) of the neuroasymptomatic individuals and 20% (2/10) of the individuals with HAD had elevated albumin ratios. ART significantly decreased albumin ratios in both neuroasymptomatic individuals and in patients with HAD. CONCLUSION: These findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.
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Complejo SIDA Demencia , Infecciones por VIH , VIH-1 , Barrera Hematoencefálica , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Proteínas de NeurofilamentosRESUMEN
Background: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined. Method: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools. Findings: Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not. Conclusions: HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos T CD4-Positivos/inmunología , COVID-19/inmunología , Inmunidad/inmunología , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Estudios Seroepidemiológicos , Suecia , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0241104.].
RESUMEN
BACKGROUND: Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. METHODS: Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. RESULTS: We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. CONCLUSIONS: We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.