ABSTRACT
As aspergillosis is a well-known complication of severe influenza, we suggest that SARS-CoV-2 might be a risk factor for invasive aspergillosis (IA). We report the case of an 87 year-old woman, with no history of immune deficit, admitted in our emergency room for severe respiratory distress. Coronavirus disease 2019 (COVID-19) diagnosis was confirmed by a SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) on nasal swab. On day 14, pulmonary examination deteriorated with haemoptysis and a major increase of inflammatory response. A computed tomography (CT) scan revealed nodules highly suggestive of IA. Aspergillus antigen was found highly positive in sputum and blood, as was Aspergillusspp PCR on serum. Sputum cultures remained negative for Aspergillus. This patient died rapidly from severe respiratory failure, despite the addition of voriconazole. Considering SARS-CoV-2 acute respiratory distress syndrome (ARDS) as an acquired immunodeficiency, we report here a new case of "probable" IA based on clinical and biological arguments, in accordance with the last consensus definition of invasive fungal disease. On a routine basis, we have detected 30% of aspergillosis carriage (positive culture and antigen in tracheal secretions) in critically ill patients with COVID-19 in our centre. Further studies will have to determine whether sputum or tracheal secretions should be systematically screened for fungal investigations in intensive care unit (ICU) COVID-19 patients to early diagnose and treat aspergillosis.
Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Invasive Pulmonary Aspergillosis/complications , Pneumonia, Viral/diagnosis , Aged, 80 and over , Antigens, Fungal/analysis , Antigens, Fungal/blood , Aspergillus/genetics , Aspergillus/immunology , Aspergillus/isolation & purification , Betacoronavirus/enzymology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/complications , Fatal Outcome , Female , Humans , Invasive Pulmonary Aspergillosis/diagnosis , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/etiology , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , SARS-CoV-2 , Sputum/microbiologyABSTRACT
Deciphering the mutational patterns and/or the biomarkers that might predict clinical response in patients with myelofibrosis is primordial to make treatment decisions. In this report, we discuss the clinical history, pathological evaluation, and genomics findings in a patient with JAK2-positive myelofibrosis who developed a secondary myelodysplasia after hematopoietic stem cell transplantation and JAK1/2 inhibitor treatment. Using next-generation sequencing, a paired comparison of relapse-specific versus primary tumour mutations highlighted the dynamic clonal evolution at relapse, showing concurrently the complete eradication of the JAK2-positive clone and the expansion of a second JAK2-negative clone with additional mutations. Importantly, another unexpected finding was that myelodysplasia was not secondary to allogeneic transplantation as relapse was driven by the overgrowth of a preexisting mutated clone, probably fostered by initial treatment options. This case underlines the fact that determining the genetic changes associated with the primary disease and its evolution is crucial to accurately correlate variants frequency to treatment decision and/or treatment response.