Uncovering Prognostic Clinical Phenotypes in Children and Adolescents with SARS-CoV-2 Infection

Abstract Background Characterizing clinical phenotypes is important for classifying patients, predicting disease outcomes, and adapting treatment. We aimed to identify distinct clinical phenotypes among hospitalized children and adolescents with SARS-CoV-2 infection and to evaluate variations in prognosis across these phenotypes. Methods The DGPI (German Society of Pediatric Infectious Diseases) registry serves as a nationwide, prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection in Germany. We applied hierarchical clustering and integrated variables such as sex, SARS-CoV-2-related symptoms, pre-existing comorbidities, clinically relevant coinfection, and SARS-CoV-2 risk factors to describe distinct clinical phenotypes. Subsequently, we applied a multinomial logistic regression model to examine the association between these phenotypes and discharge status. Results The DGPI registry encompassed 6983 patients and facilitated the identification of six distinct phenotypes for children and adolescents with SARS-CoV-2. Phenotype A had a similar symptom pattern as the total sample. Predominant symptoms of patients with other phenotypes were gastrointestinal (95.9%, B), asymptomatic (95.9%, C), lower respiratory tract (49.8%, D), lower respiratory tract and ear, nose and throat (86.2% and 41.7%, E), and neurological (99.2%, F). Patients with phenotype C had lower odds of residual symptoms (OR: 0.10 [0.06, 0.15]) than those with phenotype A, whereas patients with phenotype D and E had higher odds of residual symptoms (OR: 1.33 [1.11, 1.59] and 1.91 [1.65, 2.21], respectively) than those with phenotype A. Patients with phenotype D were significantly more likely (OR: 4.00 [1.95, 8.19]) to have an unfavorable outcome, compared to patients with phenotype A. Conclusions We could show that the identified phenotypes could facilitate early risk assessment and aid in tailoring individualized patient management strategies. Key messages • Six distinct clinical phenotypes existed in children and adolescents with SARS-CoV-2 infection. • Phenotypes could assist in risk evaluation and help personalize patient care.