Haemoptysis as the first presentation of COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that profoundly challenges healthcare systems all over the world. Fever, cough and fatigue are the most commonly reported clinical symptoms. CASE PRESENTATION: A 58-year-old man presented at the emergency department with acute onset haemoptysis. On the fifth day after admission, he developed massive haemoptysis. Computed tomography (CT) angiography of the chest revealed alveolar haemorrhage, more prominent in the left lung. Flexible bronchoscopy confirmed bleeding from the left upper lobe, confirmed by a bronchial arteriography, which was successfully embolized. Nasopharyngeal swabs (NPS) tested for SARS-CoV-2 using real-time polymerase chain reaction (RT-PCR) repeatedly returned negative. Surprisingly, SARS-CoV-2 was eventually detected in bronchoalveolar lavage (BAL) fluid. CONCLUSIONS: Life-threatening haemoptysis is an unusual presentation of COVID-19, reflecting alveolar bleeding as a rare but possible complication. This case emphasises the added value of bronchoscopy with BAL in the diagnostic work-up in case of high clinical suspicion and negative serial NPS in patients presenting with severe symptoms.

Effect of 18 months elexacaftor-tezacaftor-ivacaftor on body mass index and glycemic control in adults with cystic fibrosis.

BACKGROUND & AIMS: Malnutrition and cystic fibrosis related diabetes (CFRD) are common comorbidities in cystic fibrosis (CF). Cystic fibrosis transmembrane regulator (CFTR) modulators have shown beneficial effects on respiratory status. This study aims to determine the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on body mass index (BMI) and glycemic control. METHODS: A retrospective, observational study of a cohort of 17 adult CF patients was conducted at the CF reference center of Ghent University Hospital. BMI evolution was analyzed 18 months before and 0, 3, 6, 12 and 18 months after the start of ETI. The evolution of insulin dependence and the 2 h oral glucose tolerance test (OGTT) results were described until 36 months after start of ETI, in a small subgroup of ten patients with CFRD or impaired glucose tolerance (IGT). RESULTS: A significant increase in mean BMI of 1.2 kg/m2 (±1.3 SD) was observed. Most weight gain was observed in the first 3 months after starting treatment. This effect was sustained during the observed period of 18 months. Six patients had insulin dependent CFRD, of which three were able to stop insulin after starting ETI. Two patients with CFRD treated with dietary measures showed an initial normalization of the 2 h OGTT, but deterioration at 36 month follow-up. CONCLUSIONS: After initiation of ETI an increase in BMI was observed in adults with CF. ETI can have a beneficial impact on glucose metabolism in patients with CFRD, leading to a possible need for reduction or cessation of insulin therapy.

Urinary sodium/creatinine ratio is a predictor for fractional sodium excretion and related to age in patients with cystic fibrosis.

Electrolyte disturbances are common in patients with cystic fibrosis (CF). Current guidelines on monitoring sodium status are based on research in a small group of infants and require blood sampling. The aim of this study was to evaluate urinary salt parameters as a surrogate for sodium-status in different age-groups. Blood and urine samples for electrolytes were collected from 222 patients followed at the Ghent University Hospital CF-center. Fractional sodium excretion (FENa) and several urinary parameters were calculated. Clinical characteristics did not differ according to sodium status, defined as FENa <0.5%. ROC analysis demonstrated that sodium/creatinine ratio (UNa/Creat) predicted the sodium status most accurately with high sensitivity and specificity (97 and 91% respectively). The UNa/Creat cut-off predicting a FENa <0.5% differed significantly according to age. The UNa/Creat is an excellent marker for the sodium status defined as a FENa <0.5%. However, different cut-offs according to age category should be applied.

Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment.

GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).

Phenotype of Gc-globulin influences the macrophage activating factor (MAF) levels in serum.

BACKGROUND: Gc-globulin is a polymorphic protein with three phenotypes: Gc 1-1, Gc 2-1 and Gc 2-2. Deglycosylation of Gc-globulin results in a Gc-macrophage activating factor (Gc-MAF). This study investigated the potential of MAF as a tumour marker and the influence of Gc-phenotypes on serum MAF-concentrations. METHODS: Gc-phenotype of 98 healthy individuals and 60 cancer patients was determined. MAF-levels of healthy individuals and cancer patients were analysed according to their Gc-phenotype using a Helix pomatia agglutinin-based ELISA. ROC curves analysed the efficiency of MAF as a tumour marker. RESULTS: MAF-levels between controls and patients were significantly different (p<0.001). No phenotypic differences were found in the patients. In comparison with the controls, MAF-values were significantly lower in cancer patients carrying Gc 1-1 (p<0.01) and Gc 2-1 (p<0.001). No difference was observed in Gc 2-2 phenotype. Diagnostic accuracy of MAF as a tumour marker also demonstrated pronounced differences between Gc-phenotypes. CONCLUSIONS: Gc-phenotype is a confounding factor when interpreting MAF-data. The value of MAF as a tumour marker varies according to phenotype. Future studies on MAF will have to consider the effect of Gc-phenotype.