Corrigendum to Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial [EClinicalMedicine 37 (2021) 100,959]".

[This corrects the article DOI: 10.1016/j.eclinm.2021.100959.].

Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial.

BACKGROUND: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. METHODS: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. FINDINGS: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. INTERPRETATION: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. FUNDING: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

[Recurrent lymphocytic meningitis by herpes simplex virus type 2]. / Meningitis linfocítica recurrente por virus herpes simple tipo 2.

Recurrent lymphocytic meningitis or Mollaret's meningitis is a rare condition caused by a number of infectious, autoimmune, toxic and neoplastic diseases. Herpes simplex type 2 is the most commonly isolated agent. It usually compromises middle aged women, with a self-limited clinical presentation that resolves within a week leaving no sequelae. Its diagnosis is mainly based on nucleic acid detection on cerebrospinal fluid. Antiviral prophylaxis has not shown conclusive to avoid recurrences.

La meningitis linfocítica recurrente o meningitis de Mollaret es una entidad asociada a un gran número de etiologías infecciosas, autoinmunes, toxicológicas y neoplásicas. En la actualidad el virus herpes simple tipo 2 (HSV-2) es el agente más frecuentemente aislado. Afecta frecuentemente a mujeres de mediana edad y tiende a autolimitarse sin secuelas dentro de la primera semana de inicio de síntomas. El diagnóstico se basa en la detección de ácidos nucleicos virales en el líquido cefalorraquídeo. Al momento no se ha demostrado beneficio en el uso de tratamiento antiviral en la prevención de recurrencias.

Meningitis linfocítica recurrente por virus herpes simple tipo 2 / Recurrent lymphocytic meningitis by herpes simplex virus type 2

La meningitis linfocítica recurrente o meningitis de Mollaret es una entidad asociada a un gran número de etiologías infecciosas, autoinmunes, toxicológicas y neoplásicas. En la actualidad el virus herpes simple tipo 2 (HSV-2) es el agente más frecuentemente aislado. Afecta frecuentemente a mujeres de mediana edad y tiende a autolimitarse sin secuelas dentro de la primera semana de inicio de síntomas. El diagnóstico se basa en la detección de ácidos nucleicos virales en el líquido cefalorraquídeo. Al momento no se ha demostrado beneficio en el uso de tratamiento antiviral en la prevención de recurrencias.

Recurrent lymphocytic meningitis or Mollaret´s meningitis is a rare condition caused by a number of infectious, autoimmune, toxic and neoplastic diseases. Herpes simplex type 2 is the most commonly isolated agent. It usually compromises middle aged women, with a self-limited clinical presentation that resolves within a week leaving no sequelae. Its diagnosis is mainly based on nucleic acid detection on cerebrospinal fluid. Antiviral prophylaxis has not shown conclusive to avoid recurrences.

[Rhodococcus equi infection in AIDS patients: retrospective analysis of 13 patients in Argentina]. / Infección por Rhodococcus equi en pacientes con SIDA: Análisis retrospectivo de 13 pacientes en Argentina.

INTRODUCTION: Rhodococcus equi is a gram positive coccoid rod that causes pulmonary infections in immunosuppressed patients. METHODS: We retrospectively analyzed epidemiological, clinical, microbiological, radiological, and immunological features as well as the outcomes of 13 AIDS patients with R. equi infection. RESULTS: Between January 1994 and December 2012, 13 patients attending the AIDS department of the Infectious Diseases reference hospital in Buenos Aires were diagnosed with R. equi infection. All were men, the median age was 27 years. At the time of diagnosis, the median of CD4+ T cell counts was 11 cells/µl Twelve patients presented pulmonary disease with isolation of the microorganism from sputum or bronchoalveolar lavage; in the other patient the diagnosis was postmortem with positive culture of cerebrospinal fluid. The most frequent clinical manifestations were fever, haemoptysis, and weight loss. The predominant radiological finding was lobe consolidation with cavitation. Nine patients died after a median survival of 5.5 months. In all of them, cultures persisted positive until the last admission. The other 4 patients did continue clinical follow-ups. CONCLUSION: The insidious course of R. equi disease and the difficulties in the isolation of the microorganism contribute to the delay in the diagnosis and to the high mortality rate of this opportunistic infection.

Infección por Rhodococcus equi en pacientes con SIDA: Análisis retrospectivo de 13 pacientes en Argentina / Rhodococcus equi infection in AIDS patients: Retrospective analysis of 13 patients in Argentina

Introduction: Rhodococcus equi is a gram positive coccoid rod that causes pulmonary infections in immunosuppressed patients. Methods: We retrospectively analyzed epidemiological, clinical, microbiological, radiological, and immunological features as well as the outcomes of 13 AIDS patients with R. equi infection. Results: Between January 1994 and December 2012, 13 patients attending the AIDS department of the Infectious Diseases reference hospital in Buenos Aires were diagnosed with R. equi infection. All were men, the median age was 27 years. At the time of diagnosis, the median of CD4+ T cell counts was 11 cells/μl Twelve patients presented pulmonary disease with isolation of the microorganism from sputum or bronchoalveolar lavage; in the other patient the diagnosis was postmortem with positive culture of cerebrospinal fluid. The most frequent clinical manifestations were fever, haemoptysis, and weight loss. The predominant radiological finding was lobe consolidation with cavitation. Nine patients died after a median survival of 5.5 months. In all of them, cultures persisted positive until the last admission. The other 4 patients did continue clinical follow-ups. Conclusion: The insidious course of R. equi disease and the difficulties in the isolation of the microorganism contribute to the delay in the diagnosis and to the high mortality rate of this opportunistic infection.

Introducción: Rhodococcus equi es un cocobacilo grampositivo que provoca compromiso pulmonar en pacientes inmunodeprimidos. Métodos: En el presente trabajo se analizaron de manera retrospectiva los hallazgos epidemiológicos, clínicos, microbiológicos, imagenológicos, inmunológicos y la evolución de 13 pacientes con SIDA y enfermedad por R. equi. Resultados: Entre enero de 1994 y diciembre de 2012, 13 pacientes internados en la División de VIH/SIDA del hospital de referencia para Enfermedades Infecciosas de la ciudad de Buenos Aires egresaron con diagnóstico de enfermedad por R. equi. Todos eran varones y la mediana de edad fue 27 años. La mediana de linfocitos T CD4+ fue de 11 céls/μl Doce pacientes presentaron enfermedad pulmonar con aislamiento del microorganismo del esputo o del lavado bronco-alveolar; en el restante se recibió post mortem el cultivo positivo de líquido cefalorraquídeo. Las manifestaciones clínicas más frecuentes fueron fiebre, hemoptisis y pérdida de peso. La imagen radiológica predominante fue la consolidación con cavitación. Nueve pacientes fallecieron, con una mediana de supervivencia de 5,5 meses. En todos ellos el cultivo persistió positivo hasta la última internación. Los cuatro restantes abandonaron los controles y no pudieron ser evaluados en el tiempo. Conclusión: El curso insidioso de la enfermedad por R. equi y las dificultades en la identificación del microorganismo, contribuyen al retardo en el diagnóstico y a la elevada mortalidad de esta infección oportunista en esta población de pacientes.

[Brunner's gland adenoma: a rare tumor as cause of pyloric syndrome in an AIDS patient]. / Adenoma de glándulas de Brunner: un tumor raro como causa de sindrome pilórico en un paciente con SIDA.

Brunner's gland adenoma is a rare neoplasm that accounts for only the 0.008% of all benign duodenal tumors. Here we describe the case ofan HIV-seropositive man who developed a severe pyloric stenosis due to a Brunner's adenoma of the bulb and the first duodenal portion. Gastroduodenoscopy showed a large polypoid tumor that obstructed the pyloric region. The lesion was resected by surgery and a gastroduodenal anastomosis was made. The histopathologic examination of the surgical specimen showed a large proliferation of Brunner's glands into a large pedunculated polyp that confirmed the diagnosis of this hamartoma.

Meningitis por Candida parapsilosis en un paciente con sida. Informe del caso y revisión de los estudios publicados / Candida parapsilosis meningitis in a patient with AIDS. Report of a case and review of the literature

Antecedentes. Candida parapsilosis es una importante especie del género Candida que tiene un papel fundamental en el desarrollo de infecciones nosocomiales. En pacientes con infección por VIH, el compromiso del sistema nervioso central por hongos del género Candida es infrecuente. Caso clínico. En este artículo se presenta el caso de un paciente adulto con sida que desarrolló una meningoencefalitis por C. parapsilosis. Se describen las manifestaciones clínicas, los métodos de diagnóstico, el tratamiento antifúngico y la evolución. Conclusión. C. parapsilosis es un patógeno infrecuente como causa de meningitis en pacientes con sida. Un alto índice de sospecha y la realización de cultivos son necesarios para confirmar el diagnóstico de meningoencefalitis por levaduras del género Candida(AU)

Candida parapsilosis is an important species in the genus Candida that plays a significant role in hospitalized patients with nosocomial infections. In patients with HIV infection or AIDS, central nervous system involvement by Candida species is exceptional. Case report. Here we report a case of an acute meningoencephalitis due to C. parapsilosis in an adult patient with AIDS. We describe the clinical manifestations, the diagnosis methods, antifungal therapy and outcome. Conclusions. C. parapsilosis is uncommonly reported as a cause of meningitis in AIDS patients. A higher index of suspicion and culture is necessary to confirm the diagnosis of candidal meningoencephalitis(AU)

Candida parapsilosis meningitis in a patient with AIDS. Report of a case and review of the literature.

BACKGROUND: Candida parapsilosis is an important species in the genus Candida that plays a significant role in hospitalized patients with nosocomial infections. In patients with HIV infection or AIDS, central nervous system involvement by Candida species is exceptional. CASE REPORT: Here we report a case of an acute meningoencephalitis due to C. parapsilosis in an adult patient with AIDS. We describe the clinical manifestations, the diagnosis methods, antifungal therapy and outcome. CONCLUSIONS: C. parapsilosis is uncommonly reported as a cause of meningitis in AIDS patients. A higher index of suspicion and culture is necessary to confirm the diagnosis of candidal meningoencephalitis.

Sífilis maligna en un paciente con infección por VIH: Presentación de un caso y revisión de la literatura / Malignant syphilis in a patient infected by human immunodeficiency virus: Case report and literature review

Malignant syphilis is a rare form of secondary syphilis strongly associated with human immunodeficiency virus infection (HIV). This clinical form of the disease is characterized by atypical cutaneous ulcerative and disseminated lesions and systemic compromise that can delay the final diagnosis. There are only few reports in the medical literature about malignant lues in HIV-infected patients. Malignant syphilis should be considered in the differential diagnosis in HIV-infected patients with fever and ulcerative skin lesions. Here we describe a man who developed clinical cutaneous and systemic manifestations pathologically conirmed as malignant syphilis and we performed a review of the literature.

La sífilis maligna es una forma rara de presentación de lúes secundaria asociada a la infección por el virus de la inmunodeficiencia humana (VIH). Se caracteriza por lesiones cutáneas atípicas, ulceradas, costrosas y diseminadas, asociadas con síntomas generales inespecíficos que pueden retrasar el diagnóstico correcto. Existen sólo escasas publicaciones en la literatura médica acerca de sífilis maligna en pacientes con infección por VIH. La lúes maligna debe incluirse en el diagnóstico diferencial de los pacientes con VIH que consultan por fiebre y lesiones úlcero-costrosas diseminadas. Se describe el caso de un paciente con infección por VIH que desarrolló una sífilis maligna con confirmación diagnóstica a partir de los hallazgos histopatológicos y se realiza una revisión de la literatura científica sobre el tema.

[Malignant syphilis in a patient infected by human immunodeficiency virus. Case report and literature review]. / Sífilis maligna en un paciente con infección por VIH: Presentación de un caso y revisión de la literatura.

Malignant syphilis is a rare form of secondary syphilis strongly associated with human immunodeficiency virus infection (HIV). This clinical form of the disease is characterized by atypical cutaneous ulcerative and disseminated lesions and systemic compromise that can delay the final diagnosis. There are only few reports in the medical literature about malignant lues in HIV-infected patients. Malignant syphilis should be considered in the differential diagnosis in HIV-infected patients with fever and ulcerative skin lesions. Here we describe a man who developed clinical cutaneous and systemic manifestations pathologically confirmed as malignant syphilis and we performed a review of the literature.

Non-Hodgkin lymphomas of the oral cavity in AIDS patients in a reference hospital of infectious diseases in Argentina: report of eleven cases and review of the literature.

INTRODUCTION: Extranodal non-Hodgkin lymphoma (NHL) were commonly described in AIDS patients and are related with an atypical morphology and aggressive clinical course. MATERIALS AND METHODS: In this single institutional study we evaluated the epidemiological, clinical, immunological, virological, histopathological and the outcome of eleven HIV/AIDS patients with oral cavity lymphomas (OCL). RESULTS: Nine were males and seven intravenous drug abusers. The median of age was 33 years and the median of CD4 T cell counts at the time of diagnosis was 97 cell/µL. The majority of tumors presented as large and ulcerated masses involving the gingiva, the palate and the jaw. Six of these tumors were diffuse large B-cell lymphomas (DLBCL); three were Burkitt's lymphomas and the final case was a plasmablastic lymphoma. An association with Epstein-Barr virus (EBV) was found in three of the ten tested cases by in situ hybridization (EBER 1 and 2 probes) and immunohistochemistry (LMP-1). Human herpes virus-8 (HHV-8) was detected by polymerase chain reaction (PCR) in only one neoplasm. Six patients died without specific treatment; four received chemotherapy and highly active antiretroviral therapy (HAART) and three of them presented a prolonged survival. DISCUSSION: Combination of HAART and chemotherapy should modify the poor prognosis of AIDS patients with OCL.

Sudden blindness due to bilateral optic neuropathy associated with cryptococcal meningitis in an AIDS patient

Antecedentes. La criptococosis es una de las más frecuentes y graves enfermedades marcadoras del sida. Objetivos. Se describe el caso de un paciente con enfermedad VIH/sida avanzada y meningoencefalitis por Cryptococcus neoformans que presentó un cuadro de amaurosis bilateral aguda asociada con aumento de la presión intracraniana y neuropatía óptica. Métodos. El paciente evolucionó de manera desfavorable, falleció y en la necropsia se observaron un gran número de levaduras compatibles con Cryptococcus que infiltraban las meninges, la vía óptica y el quiasma. Conclusión. la amaurosis fue el resultado de la arachnoiditis perineurítica y de la infiltración y necrosis del nervio y quiasma óptico por levaduras de Cryptococcus(AU)

Background. Cryptococcosis is one of the most frequent and severe AIDS defining illnesses. Aims. We present a patient with advanced HIV/AIDS disease and a diffuse meningoencephalitis due to Cryptococcus neoformans. The patient developed an acute and bilateral blindness associated with high cerebrospinal fluid pressure and optic neuropathy. Methods. Post-mortem anatomopathologic study revealed a high number of Cryptococcus in the central nervous system, including the optic nerves and the optic chiasm. Conclusion. The patient's sudden visual loss appeared to be related to the perineuritic arachnoiditis and the massive invasion of the optic nerves by the fungus(AU)

Sudden blindness due to bilateral optic neuropathy associated with cryptococcal meningitis in an AIDS patient.

BACKGROUND: Cryptococcosis is one of the most frequent and severe AIDS defining illnesses. AIMS: We present a patient with advanced HIV/AIDS disease and a diffuse meningoencephalitis due to Cryptococcus neoformans. The patient developed an acute and bilateral blindness associated with high cerebrospinal fluid pressure and optic neuropathy. METHODS: Post-mortem anatomopathologic study revealed a high number of Cryptococcus in the central nervous system, including the optic nerves and the optic chiasm. CONCLUSION: The patient's sudden visual loss appeared to be related to the perineuritic arachnoiditis and the massive invasion of the optic nerves by the fungus.

Non Hodgkin's lymphoma with cutaneous involvement in AIDS patients: report of five cases and review of the literature.

Cutaneous B cell lymphoma (CBCL) is a lymphoproliferative disorder of neoplastic B cell of the skin with a wide range of clinical manifestations. Commonly, the clinical features of CBCL are plaques, nodules, or ulcerative lesions. Skin is one of the common sites for extra-nodal lymphomas in patients with AIDS and B cell type is less common than T cell type. Only recently, the existence of B cell lymphomas presenting clinically in the skin without evidence of extra-cutaneous involvement has been accepted as primary CBCL. Here, we are presenting 5 patients with cutaneous involvement in the setting of HIV/AIDS disease. Two of them were primary cutaneous non-Hodgkin lymphomas. All were CBCL; 3 were immunoblastic, 1 was plasmablastic, and the other was a Burkitt lymphoma. We analyzed the epidemiological, clinical, virological, and immunological characteristics of this group of patients.

Non Hodgkin's lymphoma with cutaneous involvement in AIDS patients: report of five cases and review of the literature

Cutaneous B cell lymphoma (CBCL) is a lymphoproliferative disorder of neoplastic B cell of the skin with a wide range of clinical manifestations. Commonly, the clinical features of CBCL are plaques, nodules, or ulcerative lesions. Skin is one of the common sites for extra-nodal lymphomas in patients with AIDS and B cell type is less common than T cell type. Only recently, the existence of B cell lymphomas presenting clinically in the skin without evidence of extra-cutaneous involvement has been accepted as primary CBCL. Here, we are presenting 5 patients with cutaneous involvement in the setting of HIV/AIDS disease. Two of them were primary cutaneous non-Hodgkin lymphomas. All were CBCL; 3 were immunoblastic, 1 was plasmablastic, and the other was a Burkitt lymphoma. We analyzed the epidemiological, clinical, virological, and immunological characteristics of this group of patients.

Disseminated nocardiosis with psoas abscess in a patient with AIDS: first reported case.

Psoas muscle abscess is an uncommon infection that have been diagnosed increasingly in the last years. We present a case of a patient with advanced human immunodeficiency virus infection who developed a disseminated infection due to Nocardia asteroides sensu stricto type VI with psoas abscess. To our knowledge no other cases of Nocardia psoas abscess in the setting of HIV infection have been reported in the literature.