Cycle threshold predicted mortality in a cohort of patients with hematologic malignancies infected with SARS-CoV-2 / El umbral de ciclado predijo la mortalidad en una cohorte de pacientes conneoplasias hematológicas infectados con SARS-CoV-2 / Microbiología clinica y enfermedades infecciosas

Abstract When a SARS-CoV-2 RT-qPCR test is performed, it may determine an indirect measureof viral load called cycle threshold (Ct). Respiratory samples with Ct <25.0 cycles are consideredto contain a high viral load. We aimed to determine whether SARS-CoV-2 Ct at diagnosis couldpredict mortality in patients with hematologic malignancies (lymphomas, leukemias, multiplemyeloma) who contracted COVID-19. We included 35 adults with COVID-19 confirmed by RT-qPCR performed at diagnosis. We evaluated mortality due to COVID-19 rather than mortalitydue to the hematologic neoplasm or all-cause mortality. Twenty-seven (27) patients survivedand 8 died. The global mean Ct was 22.8 cycles with a median of 21.7. Among the survivors,the mean Ct was 24.2, and the median Ct value was 22.9 cycles. In the deceased patients, themean Ct was 18.0 and the median Ct value was 17.0 cycles. Using the Wilcoxon Rank Sum test,we found a significant difference (p = 0.035). SARS-CoV-2 Ct measured in nasal swabs obtainedat diagnosis from patients with hematologic malignancies may be used to predict mortality.

Resumen Cuando se realiza una RT-qPCR para SARS-CoV-2, es posible determinar una medidaindirecta de la carga viral llamada umbral de ciclado (Ct). Las muestras respiratorias con Ct<25,0 ciclos se consideran de alta carga viral. Nos propusimos determinar si el Ct para SARS-CoV-2 al diagnóstico predice la mortalidad en pacientes con neoplasias hematológicas (linfomas,leucemias, mielomas) que contrajeron COVID-19. Incluimos 35 adultos con COVID-19 confirmadopor RT-qPCR al diagnóstico. Evaluamos la mortalidad por COVID-19, no la mortalidad por la neo-plasia hematológica o la mortalidad por cualquier causa. De los 35 pacientes, 27 sobrevivierony 8 fallecieron. El Ct global medio fue 22,8 ciclos con una mediana de 21,7 ciclos. Entre lossobrevivientes, el Ct medio fue 24,2 ciclos con una mediana de 22,9 ciclos. Entre los fallecidos,el Ct medio fue 18,0 y el Ct mediano fue 17,0 ciclos. Empleando la prueba de suma de rangosde Wilcoxon, encontramos una diferencia significative (p = 0,035). En pacientes con neoplasiashematológicas infectados con coronavirus, el Ct de SARS-CoV-2 medido en hisopados nasales almomento del diagnóstico podría ser utilizado para predecir la mortalidad.

[Skin lesions associated with invasive candidiasis in a neutropenic patient with acute myeloid leukemia] / Lesiones cutáneas asociadas a candidiasis invasiva en un paciente neutropénico con leucemia mieloide aguda.

A 51-year-old male with profound and prolonged neutropenia 12 days after receiving chemotherapy for an acute myeloid leukemia developed a nodular, erythematous lesion with a necrotic center on the base of the neck, associated with fever, chills, and myalgia. An invasive fungal infection was diagnosed after growth of Candia tropicalis in blood cultures. He evolved with multiple reddish papular lesions concentrated mainly on the trunk, although they also spread to the extremities. The most common skin lesions of disseminated candidiasis are erythematous-violaceous papules with vesicular centers, which, in some cases, can progress to necrosis. Other forms of cutaneous presentation of invasive candidiasis are ecthyma gangrenosum-like lesions, hemorrhagic plaques or bullae, rash resembling folliculitis, and subcutaneous nodules.

Un varón de 51 años que se encontraba con neutropenia profunda y prolongada luego de 12 días del inicio de su quimioterapia por una leucemia mieloide aguda desarrolló una lesión nodular, eritematosa y con centro necrótico en la base del cuello, asociada a fiebre, escalofríos y mialgias. Se diagnosticó infección fúngica invasiva luego del desarrollo de Candia tropicalis en los hemocultivos. Evolucionó con múltiples lesiones papulares rojizas concentradas principalmente en el tronco, aunque también extendidas a las extremidades. Las lesiones cutáneas más frecuentes de la candidiasis diseminada son pápulas eritematosas-violáceas con centros vesiculares, que, en algunos casos, pueden evolucionar a necrosis. Otras formas de presentación cutánea de la candidiasis invasiva son lesiones similares a ectima gangrenoso, placas o bullas hemorrágicas, erupción que resembla foliculitis, y nódulos subcutáneos.

Cycle threshold predicted mortality in a cohort of patients with hematologic malignancies infected with SARS-CoV-2.

When a SARS-CoV-2 RT-qPCR test is performed, it may determine an indirect measure of viral load called cycle threshold (Ct). Respiratory samples with Ct <25.0 cycles are considered to contain a high viral load. We aimed to determine whether SARS-CoV-2 Ct at diagnosis could predict mortality in patients with hematologic malignancies (lymphomas, leukemias, multiple myeloma) who contracted COVID-19. We included 35 adults with COVID-19 confirmed by RT-qPCR performed at diagnosis. We evaluated mortality due to COVID-19 rather than mortality due to the hematologic neoplasm or all-cause mortality. Twenty-seven (27) patients survived and 8 died. The global mean Ct was 22.8 cycles with a median of 21.7. Among the survivors, the mean Ct was 24.2, and the median Ct value was 22.9 cycles. In the deceased patients, the mean Ct was 18.0 and the median Ct value was 17.0 cycles. Using the Wilcoxon Rank Sum test, we found a significant difference (p=0.035). SARS-CoV-2 Ct measured in nasal swabs obtained at diagnosis from patients with hematologic malignancies may be used to predict mortality.

Descriptive analysis of Cycle Threshold in patients with hematologic malignancies infected with SARS-COV-2.

INTRODUCTION: SARS-CoV-2 has caused over 200 million documented infections, more than 4 million deaths, and unprecedented consequences worldwide. The cycle threshold (Ct), the number of amplification cycles required to obtain a product detectable through fluorescence during a quantitative RT-PCR test, is an indirect measurement of viral load. Patients with hematologic malignancies have an increased risk of death by the SARS-CoV-2. CASES PRESENTATION: We conducted a retrospective, observational, descriptive analysis of the Ct obtained from patients with history of hematologic malignancies who tested positive for SARS-CoV-2 in our hospital, from March 3rd, 2020, to August 17th, 2021. We used the mean Ct at diagnosis. 15 adults, with previous diagnosis of lymphomas, acute leukemias and chronic lymphocytic leukemia, were included. 9 of the 15 patients (60 %) developed pneumonia, 6 of them required supplementary oxygen and 5 mechanical ventilation. 5 patients died between 7-86 days from symptom onset. Ct was lower among the group of patients who died (15.5 cycles; SD= 2.28, CI95%= 9.17-21.86) compared with those who survived (20.2 cycles; SD= 8.87, CI95%= 13.9-26.6). Ct was also lower in the pneumonia group (18.2 cycles; SD= 2.28, CI95%= 12.98-23.51) than in the no-pneumonia group (19.3 cycles; SD= 4.11; CI95%= 8.73-29.9). DISCUSSION: Ct was lowest in severe forms of CoViD-19. Further studies with larger populations of patients with hematologic malignancies could establish the validity of Ct as a quantitative laboratory determination as a course-prediction and infectivity tool.

Introducción: SARS-CoV-2 ha causado más de 200 millones de infecciones documentadas, más de 4 millones de muertes, y consecuencias sin precedentes globalmente. El umbral de ciclado (Ct), número de ciclos de amplificación requerido para obtener un producto detectable durante una prueba cuantitativa de RT-PCR, es una medida indirecta de la carga viral. Los pacientes con enfermedades oncohematológicas tienen mayor riesgo de muerte por SARS-CoV-2. Presentación de casos: Realizamos un estudio observacional, retrospectivo y descriptivo de los valores de Ct obtenidos de pacientes con enfermedades oncohematológicas que resultaron positivos para SARS-CoV-2 en nuestro hospital, desde el 3 de marzo de 2020, hasta el 17 de agosto de 2021. Empleamos el Ct promedio al diagnóstico. Fueron incluidos 15 adultos, con diagnóstico de linfomas, leucemias agudas y leucemia linfocítica crónica. 9 pacientes (60 %) desarrollaron neumonía, 6 requirieron oxígeno suplementario y 5 ventilación mecánica. 5 murieron a los 7-86 días desde el inicio de síntomas. Ct fue menor entre los pacientes que murieron (15.5 ciclos; DS= 2.28, IC95%= 9.17-21.86), comparado con los que sobrevivieron (20.2 ciclos; DS= 8.87, IC95%= 13.9-26.6). La misma tendencia se observó en el grupo de los que desarrollaron neumonía (18.2 ciclos; DS= 2.28, IC95%= 12.98-23.51), comparado con lo que no tuvieron neumonía (19.3 ciclos; DS= 4.11; IC95%= 8.73-29.9). Discusión: El valor de Ct fue más bajo en las formas más graves de CoViD-19. Estudios adicionales con poblaciones mayores de pacientes con enfermedades oncohematológicas podrían establecer la validez de Ct como determinación cuantitativa de laboratorio útil como predictora de evolución e infectividad.

Screening for SARS-COV-2 Using RT-qPCR in Patients with Hematologic Neoplasms Receiving Chemotherapy.

It has been recommended that patients with leukaemias and lymphomas undergo universal screening for SARS-COV-2 using RT-qPCR before each treatment on the grounds of their high risk of experiencing severe forms of COVID-19. This raises a conflict with different recommendations which prioritise testing symptomatic patients. We found that among 56 RT-qPCR obtained in asymptomatic patients with hematologic neoplasms before chemotherapy administration, 2 (3.5%) were positive. A negative result did not exclude SARS-COV-2 infection in 1 patient (1.8%). It is unclear what the benefit of screening for SARS-COV-2 using RT-qPCR in patients with hematologic neoplasms who receive chemotherapy is.

Clinical Course of COVID-19 and Cycle Threshold in Patients with Haematological Neoplasms.

The SARS-CoV-2 viral load in a respiratory sample can be inversely quantified using the cycle threshold (Ct), defined as the number of amplification cycles required to detect the viral genome in a quantitative PCR assay using reverse transcriptase (RT-qPCR). It may be classified as high (Ct < 25), intermediate (25-30) and low (Ct > 30). We describe the clinical course of 3 patients with haematological neoplasms who contracted COVID-19. None of them had been vaccinated. Firstly, a 22-year-old male with a refractory acute lymphoblastic leukaemia experienced an oligosymptomatic COVID-19 and had a Ct of 23 with an ascending curve. Another male, aged 23, had recently begun treatment for a promyelocytic leukaemia. He had a subacute course with high oxygen requirements. His Ct dropped from 28, when he only experienced fever, to 14.8, during the most critical period and on the edge of ventilatory support. Viral clearance was documented 126 days after the beginning of the symptoms. Finally, a 60-year-old male had received rituximab as maintenance therapy for a follicular lymphoma 3 months before contracting COVID-19. He had a fulminant course and required mechanical ventilation a few days later. We highlight the association between the course of CoViD-19 and the Ct. Viral shedding was longer than in immunocompetent hosts.

Neutropenic fever of unknown origin and disseminated granulomatous disease in a patient with acute lymphoblastic leukemia.

An 18-year-old male was admitted for his second induction chemotherapy treatment for an acute lymphoblastic leukaemia with cyclophosphamide, cytarabine, and mercaptopurine. He presented with high fever, abdominal pain, non-bloody diarrhoea, portal hypertension and leukopenia. Stool sample analysis, blood cultures and extensive work-up were negative. The only microbiologic evidence was the presence of cytomegalovirus DNA detected by PCR. A profound hypogammaglobulinemia was documented. Pathology material reported non-caseating granulomas in liver, bone marrow, duodenum and colon with negative cytomegalovirus immunostaining. What is your diagnosis?

Un varón de 18 años se internó para recibir el segundo ciclo de inducción por una leucemia linfoblástica aguda con ciclofosfamida, citarabina y mercaptopurina. Desarrolló fiebre alta, dolor abdominal, diarrea no sanguinolenta, hipertensión portal y leucopenia. El análisis de materia fecal, cultivos de sangre y una evaluación exhaustiva fueron negativas. La única evidencia microbiológica fue la detección de ADN de citomegalovirus en sangre por PCR. También se documentó una hipogamaglobulinemia profunda. El material de patología reportó granulomas no caseificantes en hígado, médula ósea, duodeno y colon con inmunohistoquímica negativa para citomegalovirus. ¿Cuál es su diagnóstico?

[Hepatitis associated aplastic anemia during SARS-CoV-2 pandemic]. / Anemia aplásica asociada a hepatitis durante la pandemia por SARS-CoV-2.

The hepatitis-associated aplastic anemia is one of the acquired bone marrow failure syndromes. It is a stereotyped form of presentation of aplastic anemia and accounts for 2 - 5 % of the cases in the West. Its treatment, which does not differ from that of aplastic anemia, consists of immunosuppression when bone marrow transplant is not possible. Nonetheless, during the SARS-CoV-2 pandemic, recommendations restricting the use of antithymocyte globulin to those cases with the highest risk of death have been issued, since the prognosis of CoViD-19 tends to be worse if administered. We present an otherwise-healthy 18-year-old male who was diagnosed with a hepatitis-associated aplastic anemia and received a personalized treatment following these recommendations.

La anemia aplásica asociada a hepatitis es uno de los síndromes de fallo medular adquirido. Es una forma estereotipada de presentación de la anemia aplásica adquirida y representa el 2 - 5 % de los casos en occidente. Su tratamiento, que no difiere del de la anemia aplásica adquirida, consiste en inmunosupresión cuando el trasplante de células progenitoras hematopoyéticas no es posible. Sin embargo, durante la pandemia por SARS-CoV-2 se han publicado recomendaciones mediante las cuales se restringe el uso de globulina antitimocítica para aquellos casos con riesgo de muerte porque el pronóstico de la CoViD-19 tiende a ser peor con su uso. Presentamos el caso de un varón de 18 años previamente sano a quien se le diagnosticó una anemia aplásica asociada a hepatitis y se le personalizó el tratamiento acorde a estas recomendaciones.