Open Forum Infect Dis
. 2021 Apr 16;8(6):ofab195.
doi: 10.1093/ofid/ofab195. eCollection 2021 Jun.
Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients
Annukka A R Antar 1 , Tong Yu 1 , Nora Pisanic 2 , Razvan Azamfirei 1 , Jeffrey A Tornheim 1 , Diane M Brown 1 , Kate Kruczynski 2 , Justin P Hardick 1 , Thelio Sewell 1 , Minyoung Jang 1 , Taylor Church 1 , Samantha N Walch 1 , Carolyn Reuland 1 , Vismaya S Bachu 1 , Kirsten Littlefield 3 , Han-Sol Park 3 , Rebecca L Ursin 4 , Abhinaya Ganesan 3 , Oyinkansola Kusemiju 1 , Brittany Barnaba 1 , Curtisha Charles 1 , Michelle Prizzi 1 , Jaylynn R Johnstone 1 , Christine Payton 1 , Weiwei Dai 1 , Joelle Fuchs 1 , Guido Massaccesi 1 , Derek T Armstrong 5 , Jennifer L Townsend 1 , Sara C Keller 1 , Zoe O Demko 1 , Chen Hu 6 , Mei-Cheng Wang 7 , Lauren M Sauer 8 , Heba H Mostafa 4 , Jeanne C Keruly 1 , Shruti H Mehta 9 , Sabra L Klein 3 4 , Andrea L Cox 1 3 6 , Andrew Pekosz 3 , Christopher D Heaney 2 9 10 , David L Thomas 1 , Paul W Blair 1 , Yukari C Manabe 1 3
Affiliations
- PMID: 34095338
- PMCID: PMC8083254
- DOI: 10.1093/ofid/ofab195
Abstract
Background: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.
Methods: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.
Results: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; P = .020) and body mass index (BMI) ≥25 kg/m2 (aHR, 0.37; 95% CI, 0.18-0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; P = .044).
Conclusions: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
Keywords: COVID-19; RT-PCR; SARS-CoV-2; antibody; viral RNA.