CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

853

Long COVID in Children Is Associated With Lower Anti-RBD IgG/IgA and Neutralizing Antibody Levels Jon Izquierdo-Pujol 1 , Sara Morón-López 1 , Núria Pedreño 1 , Tetyana Pidkova 1 , Victor Urrea 1 , Judith Dalmau 1 , Alba Gonzalez-Aumatell 2 , Clara Carreras-Abad 2 , Maria Mendez 2 , Carlos Rodrigo 2 , Julià Blanco 1 , Jorge Carrillo 1 , Benjamin Trinité 1 , Javier Martinez-Picado 1 1 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 2 Hospital Germans Trias i Pujol, Barcelona, Spain Background: Most people recover quickly after SARS-CoV-2 acute infection; however, a significant percentage can develop long-term persistent symptoms, a condition known as long COVID, post-acute sequelae of SARS-CoV-2 (PASC) or Post-COVID-19 Condition (PCC). One of the main hypotheses on the underlying mechanism is the dysregulation of immune and inflammatory responses that persists after the acute infection. Most studies are focused on adults, neglecting cases in children and young people (CYP), where mechanisms may differ. Here, we analyzed the humoral and neutralizing antibody response in pediatric population with and without long COVID. Methods: We analyzed 131 blood samples from the pediaCOVID cohort (Hospital Germans Trias i Pujol), which includes 108 children/adolescents diagnosed with long COVID and 23 control CYP. An in-house ELISA was used to measure SARS-CoV-2 specific IgG and IgA antibody plasma levels (Anti-S2, Anti-RBD and Anti-N). In addition, neutralizing antibody levels were measured using a luciferase-reporter lentiviral pseudovirus assay, expressing SARS-CoV-2 S protein. Results: The long COVID cohort had a median age of 14.3 (IQR, 12.5-15.2) and 69.1% of female participants (no differences with control cohort). Patients had a median of 10 symptoms associated with long COVID (IQR, 7-16). The most common symptoms were asthenia/fatigue, (98%), neurocognitive disorders (84%) and brain fog (82%). CYP with long COVID had significant lower levels of both anti-RBD IgG and IgA antibodies compared to the control cohort (p-value < 0.0001 and 0.0332, respectively). Consistently, children and adolescents with long COVID had significant lower levels of neutralizing antibodies against the D614G variant compared to the control cohort (p-value: 0.0064). However, plasma levels of both anti-S2 and anti-N antibodies remained similar to the control group. Conclusion: Our study is the first to report antibody levels in CYP with long COVID. These results indicate that, in our cohort, CYP with long COVID had lower antibody response against the RBD of SARS-CoV-2, along with less neutralizing activity. Further experiments are needed to assess the reason and how this could impact the development of long COVID and its associated symptoms. Importantly, the lower anti-RBD antibody response could provide a potential biomarker for the diagnosis of long COVID in the pediatric population. Characterization of Circulating Biomarkers Levels in Participants With Long COVID Ninon Marmont 1 , Alejandro Garcia Leon 1 , Grace Kenny 1 , Colette Gaillard 1 , Eoghan de Barra 2 , Eoin Feeney 1 , Stefano Savinelli 1 , Mary Horgan 3 , Obada Yousif 4 , Aoife G. Cotter 1 , Patrick Mallon 1 1 University College Dublin, Dublin, Ireland, 2 Royal College of Surgeons in Ireland, Dublin, Ireland, 3 Cork University Hospital, Cork, Ireland, 4 Wexford General Hospital, Wexford, Ireland Background: Post-acute sequelae of COVID19 or 'Long COVID' is a common but heterogenous condition associated with significant morbidity. Its pathogenesis remains poorly understood, with a number of different clinical phenotypes reported. We aimed to characterize host inflammatory responses by identifying inflammatory patterns and their association with demographic factors, comorbidities, and symptoms. Methods: In plasma from individuals with PCR-confirmed COVID-19 diagnosed with Long COVID (symptoms ≥4 weeks post-acute COVID-19), part of the All Ireland Infectious Diseases Cohort study, we measured 57 biomarkers mapped

852

Predictors of Long COVID in Adults With Untreated Mild-To-Moderate COVID-19 Teresa H Evering 1 , Pooja T. Saha 2 , Carlee Moser 2 , Nikolaus Jilg 3 , Rachel A. Bender Ignacio 4 , Prasanna Jagannathan 5 , Katya Corado 6 , Kevin Wongsodirdjo 2 , Justin Ritz 2 , Jonathan Z. Li 7 , Davey M. Smith 8 , Michael D. Hughes 2 , Judith S. Currier 9 , Kara W. Chew 9 , for the ACTIV-2/A5401 Study Team 1 Weill Cornell Medicine, New York, NY, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 University of Washington, Seattle, WA, USA, 5 Stanford University, Stanford, CA, USA, 6 Harbor–UCLA Medical Center, Torrance, CA, USA, 7 Brigham and Women's Hospital, Boston, MA, USA, 8 University of California San Diego, La Jolla, CA, USA, 9 University of California Los Angeles, Los Angeles, CA, USA Background: Identifying Long COVID predictors is crucial. We studied associations with Long COVID in untreated adults in the ACTIV-2/A5401 trial. Methods: Non-hospitalized adults with COVID-19 randomized to placebo within 10 days of symptom onset were analyzed. Long COVID was defined as self-reporting overall COVID-19 symptoms as present in the 4 weeks preceding study week 24 (W24) in a long-term (LT) diary, which also assessed 27 individual symptoms. Demographics, clinical and biomarker variables at day 0 (body mass index, smoking, COVID-19 vaccination, comorbidities, symptom score summed across 13 acute symptoms each graded as absent[0]/mild[1]/moderate[2]/ severe[3], anterior nasal viral RNA levels, serostatus by anti-Spike and anti nucleocapsid antibody), and inflammatory/coagulation markers (classified as above normal or tertiles of normal values) at days 0 and 28 were evaluated as predictors of Long COVID using regression models. Results: 546/702 (78%) of participants who received placebo January-August 2021 completed LT diary at W24: median age 44 years, 53% female, 99% cis-gender, 13% Black, 53% Hispanic/Latino, 15% previously vaccinated, 49% seropositive. At W24, 74/546 (14%) had Long COVID, including 55/287 (19%) women and 19/259 (7%) men. Symptoms reported by ≥40% with Long COVID were fatigue (70%), musculoskeletal pain (51%), difficulty concentrating/ thinking (42%), muscle weakness (42%), cough (41%), breathing difficulties (40%); most were mild. Of demographic/clinical variables, only female sex and higher symptom score at day 0 were significant predictors of Long COVID in univariable and multivariable analyses: female sex adjusted risk ratio (aRR) 2.40 (95% CI: 1.43, 4.04; p<0.001), symptom score aRR 1.45 per 10 point higher score (1.10, 1.90; p<0.009). The association of symptom score with Long COVID appeared different in women (aRR 1.68 per 10 point higher score) than men (aRR 0.85), p=0.050 (Figure 1A). Viral RNA measures and serostatus were not significant in multivariable analysis. Of other biomarkers, higher fibrinogen at day 28 was associated with increased risk of Long COVID (Figure 1B). Conclusion: In untreated adults with mild-to-moderate COVID-19, female sex, higher fibrinogen levels at day 28, and symptom burden at day 0 among women but not men were associated with increased risk of Long COVID. This supports sex-stratified investigations into mechanisms of Long COVID and a potential role of clotting as a risk factor.

Poster Abstracts

854

CROI 2024 262