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Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.
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BACKGROUND: Patients with COVID-19 receiving mechanical ventilation may become aggravated with a secondary respiratory infection. The aim of this study was to describe secondary respiratory infections, their predictive factors, and outcomes in patients with COVID-19 requiring mechanical ventilation. METHODS: A cohort study was carried out in a single tertiary hospital in Santiago, Chile, from 1st June to 31st July 2020. All patients with COVID-19 admitted to the intensive care unit that required mechanical ventilation were included. RESULTS: A total of 175 patients were enrolled, of which 71 (40.6%) developed at least one secondary respiratory infection during follow-up. Early and late secondary infections were diagnosed in 1.7% and 31.4% respectively. Within late secondary infections, 88% were bacterial, 10% were fungal, and 2% were of viral origin. One-third of isolated bacteria were multidrug-resistant. Bivariate analysis showed that the history of corticosteroids used before admission and the use of dexamethasone during hospitalization were associated with a higher risk of secondary infections (p = 0.041 and p = 0.019 respectively). Multivariate analysis showed that for each additional day of mechanical ventilation, the risk of secondary infection increases 1.1 times (adOR = 1.07; 95% CI 1.02-1.13, p = 0.008) CONCLUSIONS: Patients with COVID-19 admitted to the intensive care unit and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay. The number of days on MV was a risk factor for acquiring secondary respiratory infections.
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COVID-19 , Coinfecção , Infecções Respiratórias , Estudos de Coortes , Coinfecção/epidemiologia , Dexametasona , Humanos , Unidades de Terapia Intensiva , Respiração ArtificialRESUMO
BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both Pâ <â .001) in the solid organ transplant group, 41.5% and 19.2% (both Pâ <â .0001) in the autoimmune rheumatic diseases group, 43.3% (Pâ <â .001) and 21.4% (P<.01 or Pâ =â .001) in the cancer with solid tumors group, 45.5% and 28.7% (both Pâ <â .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; Pâ <â .0001), rheumatic diseases (61%; Pâ <â .001), and HIV groups (70.9%; Pâ =â .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.
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COVID-19 , Doenças Reumáticas , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Chile/epidemiologia , Humanos , Imunidade , Hospedeiro Imunocomprometido , Estudos Prospectivos , SARS-CoV-2 , Vacinas de Produtos InativadosRESUMO
BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.
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COVID-19/terapia , Intervenção Médica Precoce/métodos , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/mortalidade , COVID-19/patologia , Chile , Progressão da Doença , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Imunização Passiva/métodos , Imunização Passiva/mortalidade , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mortalidade , Respiração Artificial/mortalidade , Respiração Artificial/estatística & dados numéricos , Tempo para o Tratamento/normas , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
In this prospective, multicentric, observational study, we describe the clinical characteristics and outcomes of people living with HIV (PLHIV) requiring hospitalization due to COVID-19 in Chile and compare them with Chilean general population admitted with SARS-CoV-2. Consecutive PLHIV admitted with COVID-19 in 23 hospitals, between 16 April and 23 June 2020, were included. Data of a temporally matched-hospitalized general population were used to compare demography, comorbidities, COVID-19 symptoms, and major outcomes. In total, 36 PLHIV subjects were enrolled; 92% were male and mean age was 44 years. Most patients (83%) were on antiretroviral therapy; mean CD4 count was 557 cells/mm3. Suppressed HIV viremia was found in 68% and 56% had, at least, one comorbidity. Severe COVID-19 occurred in 44.4%, intensive care was required in 22.2%, and five patients died (13.9%). No differences were seen between recovered and deceased patients in CD4 count, HIV viral load, or time since HIV diagnosis. Hypertension and cardiovascular disease were associated with a higher risk of death (p = 0.02 and 0.006, respectively). Compared with general population, the HIV cohort had significantly more men (OR 0.15; IC 95% 0.07-0.31) and younger age (OR 8.68; IC 95% 2.66-28.31). In PLHIV, we found more intensive care unit admission (OR 2.31; IC 95% 1.05-5.07) but no differences in the need for mechanical ventilation or death. In this cohort of PLHIV hospitalized with COVID-19, hypertension and cardiovascular comorbidities, but not current HIV viro-immunologic status, were the most important risk factors for mortality. No differences were found between PLHIV and general population in the need for mechanical ventilation and death.
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COVID-19/diagnóstico , Coinfecção/imunologia , Coinfecção/virologia , Infecções por HIV/complicações , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Adulto , Negro ou Afro-Americano , Idoso , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , COVID-19/terapia , Teste Sorológico para COVID-19 , Chile/epidemiologia , Cuidados Críticos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos ProspectivosRESUMO
Resumen Introducción: Aproximadamente 50% de las personas con infección por VIH padecen de alguna patología neuro-psiquiátrica. Características intrínsecas del virus, sus complicaciones, tratamiento y el contexto socio-cultural de los infectados facilitan el desarrollo de estas co-morbilidades, que determinan, en parte, el curso y pronóstico de las personas con infección por VIH. Objetivo: Introducir en la fisiopatología, características clínicas y manejo de la patología neuro-psiquiática en la infección por VIH, centrándose en dos de sus cuadros de mayor prevalencia: el trastorno neuro-cognitivo asociado al VIH (HAND) y el trastorno depresivo mayor (TDM). Desarrollo: En general, la detección y el tratamiento precoz de la patología neuropsiquiátrica en personas con infección por VIH mejora la calidad de vida de los pacientes, el curso clínico de la infección y mejora la adherencia al tratamiento anti-retroviral, lo que constituye una herramienta importante en el control de la propagación del VIH.
Abstract Background: The prevalence of neuropsychiatric disorders in HIV infected individuals is around 50%. Despite this, these diseases are often underdiagnosed and undertreated. Direct effects of the virus, opportunistic infections, adverse effects of antiretroviral therapy and the sociocultural context of the infected persons, contribute to the development of HIV associated neurocognitive disorder (HAND) and major depressive disorder (MDD), both of which have an impact in quality of life and disease progression. Aim: To introduce physicians in the pathophysiology, clinical features and management of psychiatric disease in seropositive patients. Content: Early detection and treatment of neuropsychiatric comorbidity in HIV infected individuals improve clinical outcomes, quality of life and is an important milestone in the control of the pandemic.
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Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/epidemiologia , Qualidade de Vida , Comorbidade , PrevalênciaRESUMO
Neurological soft signs (NSS) are frequently found in severe mental disorders, such as Alzheimer's disease, schizophrenia or HIV associated neurocognitive disorder (HAND) which includes asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia. To characterize NSS in patients with HIV we examined them with respect to neuropsychological deficits typically found in the disorder. 67 HIV + patients without a history of head trauma, opportunistic infections, severe psychiatric disorders or acute confounding comorbidities of the Central nervous system (CNS) were recruited. NSS and neuropsychological deficits were examined on the Heidelberg scale and the Cambridge Neuropsychological Test Automated Battery (CANTAB), respectively. Semantic and phonemic verbal fluency were additionally established. According to NIMH and NINDS criteria, 18 patients were diagnosed with ANI and 21 with MND, 28 showed no cognitive deficits. NSS total scores were significantly correlated with several cognitive domains and NSS subscales. These correlations were confirmed when motor performance was entered as a covariate. According to our findings, NSS in HIV positive patients are significantly correlated with deficits in a broad range of neuropsychological domains. Similar findings were reported in schizophrenia, emphasizing the transdiagnostic character of NSS and supporting NSS examination in screening HIV patients for HAND.
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Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Infecções por HIV/complicações , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/etiologia , Adulto , Disfunção Cognitiva/psicologia , Infecções por HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/psicologia , Testes Neuropsicológicos , Psicologia do EsquizofrênicoRESUMO
BACKGROUND: The prevalence of neuropsychiatric disorders in HIV infected individuals is around 50%. Despite this, these diseases are often underdiagnosed and undertreated. Direct effects of the virus, opportunistic infections, adverse effects of antiretroviral therapy and the sociocultural context of the infected persons, contribute to the development of HIV associated neurocognitive disorder (HAND) and major depressive disorder (MDD), both of which have an impact in quality of life and disease progression. AIM: To introduce physicians in the pathophysiology, clinical features and management of psychiatric disease in seropositive patients. CONTENT: Early detection and treatment of neuropsychiatric comorbidity in HIV infected individuals improve clinical outcomes, quality of life and is an important milestone in the control of the pandemic.
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Transtorno Depressivo Maior , Infecções por HIV , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Prevalência , Qualidade de VidaRESUMO
Bone loss and vitamin D deficiency are common in HIV patients. However, bone health status in newly diagnosed HIV patients has not been thoroughly described. Our aim was to assess the bone mineral density (BMD), bone resorption and vitamin D status in newly diagnosed HIV patients. A prospective observational study in HIV newly diagnosed therapy-naive persons. Patients with secondary causes of osteoporosis were excluded. Bone densitometry (DXA), a bone resorption marker (CTx), 25-hydroxyvitamin D (25OHD), CD4 count and HIV viral load (VL) were done in 70 patients. Vitamin D results were compared with a group of healthy volunteers. All patients were men, mean age 31 years (19-50). Low BMD (Z score ≤ 2.0) was found in 13%, all of them in lumbar spine, and in only one patient also in femoral neck. Bone resorption was high in 16%. One out of four participants had low BMD or high bone resorption. Vitamin D deficiency (25OHD < 20 ng/mL) was found in 66%. Mean 25OHD in patients was significantly lower than in healthy volunteers (p = 0.04). No associations were found between BMD, CTx, 25OHD and VL or CD4 count. We hypothesize that HIV infection negatively affects bone health based on the results we found among newly diagnosed, therapy-naive, HIV-infected patients, without any known secondary causes of osteoporosis. Low BMD or high bone resorption, are significantly prevalent in these patients. HIV-infected patients had a higher prevalence of vitamin D deficiency than controls, which was not correlated with CD4 count or VL.
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Densidade Óssea/fisiologia , Infecções por HIV/complicações , Osteoporose/etiologia , Vitamina D/metabolismo , Adulto , Reabsorção Óssea/metabolismo , Cálcio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Estudos Prospectivos , Vitamina D/análogos & derivados , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.