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1.
AIDS ; 38(9): 1292-1303, 2024 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-38704619

RESUMEN

BACKGROUND: HIV-associated neurocognitive disorders (HAND) still affects persons with HIV (PWH) and their pathogenesis is not completely understood. We aimed to explore the association between plasma and cerebrospinal fluid (CSF) markers of blood-brain barrier (BBB) impairment and HAND in untreated PWH. DESIGN: Cross-sectional study. METHODS: We enrolled untreated PWH, who underwent blood examinations and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, tight junction proteins: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria). RESULTS: Twenty-one patients (21/78, 26.9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4 + T cells and increased CD4 + T-cell exhaustion (lower CD4 + CD127 + and CD4 + CD45RA + T-cell percentages), in comparison to individuals without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15) but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules were not associated with HAND but with a poor performance in different cognitive domains. CONCLUSION: By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PWH.


Asunto(s)
Barrera Hematoencefálica , Infecciones por VIH , Proteínas de Uniones Estrechas , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Proteínas de Uniones Estrechas/metabolismo , Infecciones por VIH/complicaciones , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Líquido Cefalorraquídeo/química , Líquido Cefalorraquídeo/metabolismo , Disfunción Cognitiva/etiología
2.
AIDS ; 38(5): 623-632, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38016163

RESUMEN

INTRODUCTION: Impairment of the gastrointestinal barrier leads to microbial translocation and peripheral immune activation, which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely and chronically-infected, combination antiretroviral therapy (cART)-naive individuals. METHODS: Fifteen people with primary HIV infection (P-HIV) and 13 with chronic HIV infection (C-HIV) c-ART-naive participants were cross-sectionally studied. Gut biopsies were analysed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 + expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3 + panγδ+Vδ1+/Vδ2+). In plasma, we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA). RESULTS: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared with C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV. CONCLUSION: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely because of a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.


Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/patología , Neutrófilos/patología , Inflamación , Colágeno , Cadherinas , ADN , Traslocación Bacteriana
3.
Clin Microbiol Infect ; 28(4): 611.e9-611.e16, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34763058

RESUMEN

OBJECTIVE: We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis. METHODS: This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale-Revised (IES-R) score. RESULTS: A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37-53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and "brain fog" (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8-6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01-1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06-0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29-1.55, p 0.85). DISCUSSION: Factors that were found to be associated with a higher risk of developing "long COVID" syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.


Asunto(s)
COVID-19 , Adulto , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Respiración Artificial , SARS-CoV-2 , Síndrome Post Agudo de COVID-19
4.
BMC Infect Dis ; 21(1): 1132, 2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34732166

RESUMEN

BACKGROUND: Despite being an uncommon cause of meningoencephalitis, West Nile virus (WNV) recently provoked significant outbreaks throughout Europe. West Nile neuroinvasive disease (WNND) is associated with significant morbidity and mortality in older and compromised individuals, while its diagnosis may be demanding for the clinician. Here discussed are three cases of WNND with a focus on the diagnostic challenges they presented due to atypical clinical presentation and laboratory findings. CASE PRESENTATION: Between July and September 2020 three patients presented to our attention with signs and symptoms compatible with meningoencephalitis. Among routine procedures, they underwent lumbar puncture and imaging. In the absence of microbiological isolates, biological samples were sent for serology and NAATs for WNV. Following diagnosis, the patients gradually recovered and were discharged either home or to rehabilitation facilities. CONCLUSIONS: The laboratory findings here discussed, in particular CSF parameters, are only partially consistent with those described in the literature, which highlights the need for further research. While serology and NAATs on blood and urine appear the most reliable techniques in the diagnostic work-up of WNND, utility of NAATs on CSF specimens is limited by the kinetics of WNV viremia in biological fluids. This report underlines that WNND should always be included in the differential diagnosis of meningoencephalitis during WNV transmission period.


Asunto(s)
Meningoencefalitis , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Anciano , Diagnóstico Diferencial , Brotes de Enfermedades , Humanos , Meningoencefalitis/diagnóstico , Fiebre del Nilo Occidental/diagnóstico , Fiebre del Nilo Occidental/epidemiología
5.
Life (Basel) ; 11(9)2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34575128

RESUMEN

BACKGROUND: Mortality rate from COVID-19 in Italy is among the world's highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the second-wave period (October 2020-January 2021) compared to the first one (February-May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate. METHODS: Data collected related to in-patients' demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics. RESULTS: A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3-28.5) and 15.9% (95% CI: 13.7-18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years. CONCLUSIONS: Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.

6.
Front Public Health ; 9: 639347, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34178914

RESUMEN

A long period of isolation was observed in patients hospitalized for COVID-19 in Milan over March-September 2020 (45; IQR: 37-54 days). A significantly shorter period would have been observed by the application of May-WHO (22, IQR: 17-30 days, P < 0.001) and October-Italian (26, IQR: 21-34 days, P < 0.001) Guidelines. The adoption of the new symptom-based criteria is likely to lead to a significant reduction in the length of the isolation period with potential social, economic and psychological benefits, particularly in the younger population with mild/moderate disease and no comorbidities. In our opinion, the release from isolation after 21 days from symptoms onset, even without a PCR diagnostic test, in most cases seems the most adequate strategy that could balance precautions to prevent SARS CoV-2 transmission and unnecessary prolonged isolation or overuse of diagnostic testing.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2
7.
J Med Virol ; 93(2): 1175-1179, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32841387

RESUMEN

Prevalence of anxiety or depression was investigated in 105 coronavirus disease 2019 (COVID-19) patients at 1 to 3 months from virological clearance by hospital anxiety and depression scale (HADS-A/D). 30% of patients displayed pathological HADS-A/D, 52.4% showed persistent symptoms. Pathological patients with HADS-A/D more commonly reported symptom persistence, even after adjustment for age, gender, and disease severity. Psychological assessments should be encouraged in COVID-19 patients' follow-up.


Asunto(s)
Ansiedad/epidemiología , COVID-19/complicaciones , COVID-19/psicología , Depresión/epidemiología , Adulto , Anciano , COVID-19/epidemiología , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios
8.
Int J Infect Dis ; 100: 67-74, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32950738

RESUMEN

OBJECTIVE: We aimed to document data on the epidemiology and factors associated with clinical course leading to death of patients hospitalised with COVID-19. METHODS: Prospective observational cohort study on patients hospitalised with COVID-19 disease in February-24th/May-17th 2020 in Milan, Italy. Uni-multivariable Cox regression analyses were performed. Death's percentage by two-weeks' intervals according to age and disease severity was analysed. RESULTS: A total of 174/539 (32.3%) patients died in hospital over 8228 person-day follow-up; the 14-day Kaplan-Meier probability of death was 29.5% (95%CI: 25.5-34.0). Older age, burden of comorbidities, COVID-19 disease severity, inflammatory markers at admission were independent predictors of increased risk, while several drug-combinations were predictors of reduced risk of in-hospital death. The highest fatality rate, 36.5%, occurred during the 2nd-3rd week of March, when 55.4% of patients presented with severe disease, while a second peak, by the end of April, was related to the admission of older patients (55% ≥80 years) with less severe disease, 30% coming from long-term care facilities. CONCLUSIONS: The unusual fatality rate in our setting is likely to be related to age and the clinical conditions of our patients. These findings may be useful to better allocate resources of the national healthcare system, in case of re-intensification of COVID-19 epidemics.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/mortalidad , Grupos Diagnósticos Relacionados , Neumonía Viral/mortalidad , Adulto , Anciano , COVID-19 , Femenino , Mortalidad Hospitalaria , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , SARS-CoV-2 , Adulto Joven
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