Aspergilosis pulmonar asociada a COVID-19 en pacientes críticos: experiencia de un hospital público chileno / COVID-19-associated pulmonary aspergillosis in critically ill patients: experience of a Chilean public hospital

INTRODUCCIÓN: Se han descrito coinfecciones fúngicas por Aspergillus spp. en pacientes críticos cursando una infección por COVID-19. OBJETIVOS: Describir las características clínicas, diagnóstico, tratamiento y evolución de pacientes con síndrome de distrés respiratorio agudo con COVID-19, que cursan con aspergilosis pulmonar asociada a COVID-19 (CAPA por sus siglas en inglés) en un centro hospitalario público. Pacientes y MÉTODOS: Revisión de registros clínicos durante 12 meses en pacientes con diagnóstico de CAPA mediante cultivos de muestras respiratorias o determinación de galactomanano (GM). RESULTADOS: En 11 pacientes se diagnosticó CAPA probable (score APACHE II promedio de 11,7). Las muestras respiratorias se obtuvieron en 73% de los casos por lavado broncoalveolar y en 27% por aspirado endotraqueal. Se aisló A. fumigatus en 4 cultivos, A. niger, A. terreus y Aspergillus spp en una ocasión cada uno y los cultivos fueron negativos en 4 muestras. En 7 pacientes se realizó GM de muestras respiratorias, mediana: 3,6 (RIC: 1,71 - 4,4), en 10 pacientes se realizó GM sérica, mediana: 0,5 (RIC: 0,265 - 0,975) con 50% de ellas > 0,5. Dos pacientes mostraron hallazgos sugerentes de CAPA en la tomografía computada. Todos recibieron terapia anti-fúngica con voriconazol, con una duración promedio 14 días. Cuatro pacientes fallecieron. CONCLUSIONES: La presencia de CAPA debe ser un diagnóstico a considerar en pacientes críticos con COVID-19.

BACKGROUND: Aspergillus spp. fungal coinfections have been described in critically ill COVID-19 patients. AIM: To describe the clinical characteristics, diagnosis, treatment and evolution of patients with acute respiratory distress syndrome with COVID-19, who present with COVID-19 associated pulmonary aspergillosis (CAPA) in a single public hospital. METHODS: Retrospective review of clinical records during 12 months in patients diagnosed with CAPA by cultures of respiratory samples or determination of galactomannan (GM). RESULTS: Probable CAPA was diagnosed in 11 patients (average APACHE II score of 11.7). Respiratory samples were obtained in 73% of cases by bronchoalveolar lavage and in 27% by tracheal aspirate. A. fumigatus was isolated in 4 cultures, A. niger, A. terreus and Aspergillus spp on one occasion each and the cultures were negative in 4 samples. Respiratory sample GM was performed in 7 patients, median: 3.6 (IQR: 1.71 - 4.4). In 10 patients, serum GM was performed, median: 0.5 (IQR: 0.265 - 0.9 75) with 50% of them > 0.5. Two patients showed classic findings suggestive of CAPA on computed tomography. All received antifungal therapy with voriconazole, mean time 14 days. Four patients died. CONCLUSIONS: The presence of CAPA should be a diagnosis to be considered in critically ill COVID-19 patients.

Acute invasive pulmonary aspergillosis, shortly after occupational exposure to polluted muddy water, in a previously healthy subject / Aspergilose pulmonar invasiva aguda, logo após exposição ocupacional a água poluída barrenta, em indivíduo previamente saudável

Invasive pulmonary aspergillosis (IPA) predominantly occurs in severely neutropenic immunocompromised subjects. The occurrence of acute IPA after brief but massive exposure to Aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. The diagnosis was delayed in all six of the affected patients, five of whom died. We report the case of a 50-year-old HIV-negative male, a water pipeline maintenance worker, who presented with acute-onset dyspnea and fever one day after working for 2 h in a deep pit containing polluted, muddy water. Over a one-month period, his general condition deteriorated markedly, despite antibiotic therapy. Imaging showed bilateral diffuse nodules with cavitation, some of which were surrounded by ground-glass opacity suggestive of a halo sign (a hallmark of IPA). Cultures (of sputum/bronchial aspirate samples) and serology were positive for Aspergillus fumigatus. After being started on itraconazole, the patient improved. We conclude that massive exposure to Aspergillus conidia can lead to acute IPA in immunocompetent subjects.

A aspergilose pulmonar invasiva (API) ocorre predominantemente em indivíduos imunocomprometidos com neutropenia grave. A ocorrência de API aguda após exposição breve, mas maciça, a conídios de Aspergillus sp. em indivíduos previamente saudáveis já foi documentada, embora apenas seis casos tenham sido relatados. O diagnóstico foi tardio em todos os seis pacientes afetados, dos quais cinco foram a óbito. Relatamos o caso de um homem de 50 anos de idade, HIV negativo, trabalhador de manutenção de tubulação de água, que apresentou dispneia e febre de início agudo um dia após trabalhar 2 h em uma vala funda contendo água poluída e barrenta. Num período de um mês, seu estado geral se deteriorou acentuadamente, apesar da antibioticoterapia. Exames de imagem mostraram nódulos bilaterais difusos com cavitação, alguns dos quais circundados por opacidade em vidro fosco sugestiva de sinal do halo (uma característica da API). As culturas (de amostras de escarro/aspirado brônquico) e a sorologia foram positivas para Aspergillus fumigatus. Após iniciado o tratamento com itraconazol, o paciente melhorou. Concluímos que a exposição maciça a conídios de Aspergillus pode levar a API em indivíduos imunocompetentes.

Aspergilosis necrotizante crónica en un paciente con secuelas de tuberculosis pulmonar / Chronic necrotizing aspergillosis in a patient with pulmonary tuberculosis sequelae

Aspergillus fumigatus is the causative agent of differents pathologies in the human being: aspergilloma, allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis and invasive aspergillosis. In chronic necrotizing aspergillosis there is local invasion of the lung tissue and parenchyma destruction. Chronic necrotizing aspergillosis is different from invasive aspergillosis, because the abscence of vascular invasion or dissemination. Chronic necrotizing aspergillosis is seen in middle-aged and elderly with underlying lung diseases: COPD, tuberculosis sequelae, lung resection, pneumoconiosis, radiotherapy, lung infarction or sarcoidosis. Clinical manifestations are non specific, being the most usual fever, cough, sputum production and weight loss. Incidence of chronic necrotizing aspergillosis is unknown in Chile. Chronic necrotizing aspergillosis can produce death. It requires early diagnosis and treatment. In a patient with a predisposing disease and with prolonged fever and consuntive status, diagnosis of chronic necrotizing aspergillosis should be considered. We present a patient with chronic necrotizing aspergillosis attended at Instituto Nacional del Tórax (Thorax National Institute) in Santiago.

Aspergillus fumigatus puede causar diferentes patologías en el ser humano: aspergiloma, aspergilosis broncopulmonar alérgica, aspergilosis necrotizante crónica, aspergilosis invasora. En la aspergilosis necrotizante crónica hay invasión local del parénquima y destrucción. A diferencia de la aspergilosis invasora no invade vasos sanguíneos ni se disemina a otros órganos. La aspergilosis necrotizante crónica se presenta en pacientes de edad media o ancianos con patología pulmonar previa: EPOC, secuelas de tuberculosis, resección pulmonar, neumoconiosis, radioterapia, infarto pulmonar o sarcoidosis. La clínica es indolente e inespecífica, con fiebre, tos, expectoración y baja de peso. Se desconoce la incidencia de aspergilosis necrotizante crónica en nuestro medio. La aspergilosis necrotizante crónica es potencialmente fatal, por lo que requiere de un diagnóstico y tratamiento oportuno. Creemos que, debe considerarse esta entidad ante un cuadro consuntivo y febril prolongado, en pacientes con enfermedades predisponentes que producen una leve baja de la inmunidad. Describimos el caso de un paciente atendido en el Instituto Nacional del Tórax.