Distinct phenotypes of platelet, monocyte, and neutrophil activation occur during the acute and convalescent phase of COVID-19

SARS-CoV-2 has spread rapidly worldwide, causing the COVID-19 pandemic. Platelet activation and platelet-leukocyte complex formation are proposed to contribute to disease progression. Here, we report platelet and leukocyte activation during acute and convalescent COVID-19 in patients recruited between May-July 2020. Blood samples were analyzed by flow cytometry and ELISA using paired comparison between inclusion (day 0) and 28 days later. The majority of patients were mildly or moderately ill with significantly higher cytokine levels (IL-6 and IL-10) on day 0 as compared with day 28. Platelet activation and granule release were significantly higher on day 0 compared with day 28, as determined by ADP- or thrombin-induced surface CD62P expression, baseline released CD62P, and thrombin-induced platelet-monocyte complex formation. Monocyte activation and procoagulant status at baseline and post activation were heterogeneous but generally lower on day 0 compared with day 28. Baseline and thrombin- or fMLF-induced neutrophil activation and procoagulant status were significantly lower on day 0 compared with day 28. We demonstrate that during the acute phase of COVID-19 compared with the convalescent phase, platelets are more responsive while neutrophils are less responsive. COVID-19 is associated with thromboembolic events where platelet activation and interaction with leukocytes may play an important role

BPI-ANCA is expressed in the airways of cystic fibrosis patients and correlates to platelet numbers and Pseudomonas aeruginosa colonization

Background: Autoantibodies to bactericidal/permeability-increasing protein (BPI), BPI-ANCA, are often present in serum of patients with cystic fibrosis (CF), and correlate to airway colonization with Pseudomonas aeruginosa. The aim of the study was to investigate if BPI-ANCA IgA is also present in the airways of CF patients, and if its presence correlates with neutrophil counts, platelets, and P. aeruginosa DNA in sputum. Methods: BPI-ANCA IgA was quantified in serum and sputum samples from adult CF patients (n = 45) by ELISA. Sputum neutrophil counts, platelets, and platelet-neutrophil complexes were assessed by flow cytometry, and P. aeruginosa DNA was analysed with RT-PCR. Results: Serum BPI-ANCA IgA was present in 44% of the study participants, and this group also had significantly enhanced BPI-ANCA levels in sputum compared to serum negative patients. Sputum levels of BPI-ANCA IgA correlated with P. aeruginosa DNA (r = 0.63, p = 0.0003) and platelet counts in sputum (r = 0.60, p = 0.0002). Conclusions: BPI-ANCA is expressed in the airways of CF patients and correlates with P. aeruginosa load and platelet counts, suggesting a link to airway inflammation and mucosal immunity

Heparin-binding protein in sputum as a marker of pulmonary inflammation, lung function, and bacterial load in children with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is associated with bacterial pulmonary infections and neutrophil-dominated inflammation in the airways. The aim of this study was to evaluate the neutrophil-derived protein Heparin-binding protein (HBP) as a potential sputum marker of airway inflammation and bacterial load. Methods Nineteen CF patients, aged 6–18 years, were prospectively followed for 6 months with sputum sampling at every visit to the CF clinic. A total of 41 sputum samples were collected. Sputum-HBP was analysed with ELISA, neutrophil elastase activity with a chromogenic assay, and total bacterial load with RT-PCR of the 16 s rDNA gene. Data were compared to lung function parameters and airway symptoms. Results HBP and elastase correlated to a decrease in FEV1%predicted compared to the patients´ individual baseline pulmonary function (∆FEV1), but not to bacterial load. Area under the receiver operating characteristic curve values for the detection of > 10% decrease in ∆FEV1 were 0.80 for HBP, 0.78 for elastase, and 0.54 for bacterial load. Conclusions Sputum HBP is a promising marker of airway inflammation and pulmonary function in children with CF

Activity of airway antimicrobial peptides against cystic fibrosis pathogens

Antimicrobial peptides are important players of the innate host defence against invading microorganisms. The aim of this study was to evaluate the activity of airway antimicrobial peptides against the common cystic fibrosis (CF) pathogen Pseudomonas aeruginosa, and to compare it to the emerging multi-drug resistant CF pathogens Achromobacter xylosoxidans and Stenotrophomonas maltophilia. Clinical bacterial isolates from CF patients were used, and the antimicrobial activity of human beta-defensin 2 and 3, LL37 and lysozyme was evaluated using radial diffusion assay and viable counts. The cell surface zeta potential was analysed to estimate the net charge at the bacterial surface. Of the bacterial species included in the study, A. xylosoxidans was the most resistant to antimicrobial peptides, whereas P. aeruginosa was the most susceptible. The net charge of the bacterial surface was significantly more negative for P. aeruginosa compared to A. xylosoxidans, which may in part explain the differences in susceptibility