ImportanceIdentifying undetected clinical signs is imperative in the prevention of SARS-CoV-2.ObjectiveTo establish the prevalence of clinical gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. Clinical outcomes and recovery rates associated with gustatory and olfactory dysfunctions were also assessed.DesignA prospective study was performed in 80 patients admitted to Hospital Clínic of Barcelona (Spain) for COVID-19 pneumonia. Patients were re-evaluated in the ward daily until discharge. Gustatory and olfactory dysfunction symptoms were retrospectively collected from emergency room (ER) charts after first assessments. Follow-up was performed in telemedicine consultation.SettingThe single-centre study was performed in a hospitalisation ward at a university hospital.ParticipantsConsecutive patients meeting hospitalisation criteria for COVID-19 pneumonia were eligible. Study exclusion criteria were patients who could not speak, had previous gustatory and olfactory dysfunctions or whose PCR tests for SARS-CoV-19 were negative.InterventionsSystematic assessment of gustatory and olfactory symptoms with standardised questions.Outcome(s)Prevalence of gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia.ResultsOf the 80 study subjects, 62.5% were male and the median age was 57 years. Half of the cohort (n=40) presented with comorbidities. The prevalence of chemosensitive disorder was 73.8% (n=59) (95% CI: 63.8 to 83.8), although self-reported symptoms were recorded in only 26.3% (n=21) of patients in the ER. Gustatory and olfactory dysfunctions were observed in 58.8% (n=47) and 55% (n=44) of cases, respectively. They were also the first symptoms in 25% (n=20) of patients. Anosmia was associated with ageusia, OR: 7, 95% CI: 2.3 to 21.8, p=0.001). No differences in clinical outcomes were observed when patients with and without gustatory and olfactory dysfunctions were compared. Recovery rates were 20% (n=10) and 85% (n=42) at days 7 and 45, respectively.ConclusionThe prevalence of gustatory and olfactory dysfunctions in COVID-19 pneumonia was much higher than in self-report. Presence of gustatory and olfactory dysfunctions was not a predictor of clinical outcomes.
BackgroundChimeric antigen receptor (CAR)-T cell-based immunotherapy constitutes a revolutionary advance for treatment of relapsed/refractory hematological malignancies. Nevertheless, cytokine release and immune effector cell-associated neurotoxicity syndromes are life-threatening toxicities in which the endothelium could be a pathophysiological substrate. Furthermore, differential diagnosis from sepsis, highly incident in these patients, is challenging. Suitable laboratory tools could be determinant for their appropriate management.MethodsSixty-two patients treated with CAR-T cell immunotherapy for hematological malignancies (n=46 with CD19-positive diseases, n=16 with multiple myeloma) were included. Plasma samples were obtained: before CAR-T cell infusion (baseline); after 24–48 hours; at suspicion of any toxicity onset and 24–48 hours after immunomodulatory treatment. Biomarkers of endothelial dysfunction (soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble TNF receptor 1 (sTNFRI), thrombomodulin (TM), soluble suppression of tumorigenesis-2 factor (ST2), angiopoietin-2 (Ang-2)), innate immunity activation (neutrophil extracellular traps (NETs), soluble C5b-9 (sC5b-9)) and hemostasis/fibrinolysis (von Willebrand Factor antigen (VWF:Ag), ADAMTS-13 (A13), α2-antiplasmin (α2-AP), plasminogen activator inhibitor-1 antigen (PAI-1 Ag)) were measured and compared with those in cohorts of patients with sepsis and healthy donors.ResultsPatients who developed CAR-T cell toxicities presented increased levels of sVCAM-1, sTNFRI and ST2 at the clinical onset versus postinfusion values. Twenty-four hours after infusion, ST2 levels were good predictors of any CAR-T cell toxicity, and combination of ST2, Ang-2 and NETs differentiated patients requiring intensive care unit admission from those with milder clinical presentations. Association of Ang-2, NETs, sC5b-9, VWF:Ag and PAI-1 Ag showed excellent discrimination between severe CAR-T cell toxicities and sepsis.ConclusionsThis study provides relevant contributions to the current knowledge of the CAR-T cell toxicities pathophysiology. Markers of endotheliopathy, innate immunity activation and hemostatic imbalance appear as potential laboratory tools for their prediction, severity and differential diagnosis.
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