Herbert, CarlyAntar, Annukka A RBroach, JohnWright, ColtonStamegna, PamelaLuzuriaga, KatherineHafer, NathanielMcManus, David DManabe, Yukari CSoni, Apurv2024-08-302024-08-302024-07-05Herbert C, Antar AAR, Broach J, Wright C, Stamegna P, Luzuriaga K, Hafer N, McManus DD, Manabe YC, Soni A. Relationship between acute SARS-CoV-2 viral clearance with Long COVID Symptoms: a cohort study. medRxiv [Preprint]. 2024 Jul 5:2024.07.04.24309953. doi: 10.1101/2024.07.04.24309953. PMID: 39006428; PMCID: PMC11245049.10.1101/2024.07.04.2430995339006428https://hdl.handle.net/20.500.14038/53740This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Introduction: The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown. Methods: A total of 7361 asymptomatic community-dwelling people enrolled in the Test Us at Home parent study between October 2021 and February 2022. Participants self-collected anterior nasal swabs for SARS-CoV-2 RT-PCR testing every 24-48 hours for 10-14 days, regardless of symptom or infection status. Participants who had no history of COVID-19 at enrollment and who were subsequently found to have ≥1 positive SARS-CoV-2 RT-PCR test during the parent study were recontacted in August 2023 and asked whether they had experienced long COVID, defined as the development of new symptoms lasting 3 months or longer following SARS-CoV-2 infection. Participant's cycle threshold values were converted into viral loads, and slopes of viral clearance were modeled using post-nadir viral loads. Using a log binomial model with the modeled slopes as the exposure, we calculated the relative risk of subsequently developing long COVID with 1-2 symptoms, 3-4 symptoms, or 5+ symptoms, adjusting for age, number of symptoms, and SARS-CoV-2 variant. Adjusted relative risk (aRR) of individual long COVID symptoms based on viral clearance was also calculated. Results: 172 participants were eligible for analyses, and 59 (34.3%) reported experiencing long COVID. The risk of long COVID with 3-4 symptoms and 5+ symptoms increased by 2.44 times (aRR: 2.44; 95% CI: 0.88-6.82) and 4.97 times (aRR: 4.97; 95% CI: 1.90-13.0) per viral load slope-unit increase, respectively. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance during acute disease than those who never developed long COVID (8.65 [95% CI: 8.28-9.01] vs. 10.0 [95% CI: 9.25-10.8]). The slope of viral clearance was significantly positively associated with long COVID symptoms of fatigue (aRR: 2.86; 95% CI: 1.22-6.69), brain fog (aRR: 4.94; 95% CI: 2.21-11.0), shortness of breath (aRR: 5.05; 95% CI: 1.24-20.6), and gastrointestinal symptoms (aRR: 5.46; 95% CI: 1.54-19.3). Discussion: We observed that longer time from peak viral load to viral RNA clearance during acute COVID-19 was associated with an increased risk of developing long COVID. Further, slower clearance rates were associated with greater number of symptoms of long COVID. These findings suggest that early viral-host dynamics are mechanistically important in the subsequent development of long COVID.enThe copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/COVID-19PASCSARS-CoV-2cycle thresholdlong COVIDpost-acute sequelae of COVID-19 infectionviral clearanceviral persistenceInfectious Diseases (except HIV/AIDS)UMCCTS fundingPreprintmedRxiv : the preprint server for health sciences