Snapshot of long COVID in young adults: fast screening using electronic noses

Abstract

Background: Long COVID (LC) is a multisystemic condition characterized by persistent symptoms following SARS-CoV-2 infection. Although most research focuses on older or hospitalized individuals, young adults are frequently overlooked despite significant effects on their academic, professional, and social functioning. Methods: This cross-sectional study evaluated 78 university students (median age 20 years; 56.4% female) with prior COVID-19 infection, classified according to the WHO Delphi consensus definition. Sociodemographic, clinical, and spirometry data were collected, and exhaled breath samples were analyzed using an electronic nose system (e-Nose) under controlled conditions. Chemometric and machine learning techniques—Principal Component Analysis (PCA), Partial Least Squares–Discriminant Analysis (PLS-DA), Canonical Analysis of Principal Coordinates (CAP), and Random Forest (RF)—were applied to identify LC-associated volatile organic compound (VOC) patterns. Findings: LC prevalence was 29.5%. Acute-phase fatigue, (odds ratio) (OR = 3.22), dyspnea (OR = 6.09), nausea (OR = 3.57), and vomiting (OR = 11.37) were significantly associated with LC. Post-acute anosmia (OR = 3.65), sleep disturbances (OR = 4.34), and bradycardia were also more frequent among LC cases. All participants exhibited normal spirometry. e-Nose data revealed distinct group-associated VOC patterns and demonstrated promising discriminatory potential between LC and control participants (PCA variance 94.1%; CAP R² = 0.95; PLS-DA accuracy 97.4%, Q² = 0.534). The RF model achieved an out-of-bag error of 3.42% and receiver operating characteristic curve (ROC) area under the curve (AUC) of 0.966. Interpretation: Nearly one-third of young adults experienced LC despite normal pulmonary function, suggesting substantial subclinical and systemic alterations. e-Nose breath analysis represents a promising, non-invasive, and rapid approach for LC screening; while these findings support the feasibility of breath-based screening for LC, further validation in larger and independent cohorts is required before clinical implementation.