Heparin-binding motifs and biofilm formation by Candida albicans.

Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequence-based search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.

Clinical Features and Follow-up of Referred Children and Young People With Long COVID.

BACKGROUND: Patient-level data on the clinical features and outcomes of children and young people referred for possible long coronavirus disease (COVID) can guide clinicians on what to expect in managing patients and advising families. METHODS: A Post-Acute COVID Clinic for persons <21 years of age was established in October 2020. Intake was standardized and management was tailored to presenting symptoms. Data were abstracted from the charts of all patients evaluated through December 2021, and the study cohort consisted of patients who had a history of confirmed severe acute respiratory syndrome coronavirus 2 infection, had ≥1 symptom persisting for ≥12 weeks and had no pre-existing diagnosis that explained the symptoms. A structured follow-up interview was conducted in early 2022. RESULTS: A total of 104 patients were referred, 81 of whom met inclusion criteria. The median age was 14 years (interquartile range, 13-16), and most were female, White/Caucasian and had commercial health insurance. Patients reported previously good health but over half reported moderate-to-severe disability at their first visit. Two clusters of presenting symptoms-fatigue with multiple symptoms, and fatigue and headache with cardiopulmonary symptoms-were identified. Extensive routine testing did not affirm alternative diagnoses. Incident conditions-most commonly anxiety, depression and/or panic disorder; migraines; and autonomic dysfunction-were diagnosed on clinical grounds. Telephone interviews (N = 55) revealed that 78% of patients were improved by about 6 months. CONCLUSIONS: Within the limits of a single-center, referral-based, observational cohort, this study provides reassurance to patients and parents in that most cases of long COVID were self-limited. Extensive evaluations may be more useful in ruling out alternative diagnoses than in affirming specific physiologic disturbances.