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

Antar, Annukka A R; Yu, Tong; Pisanic, Nora; Azamfirei, Razvan; Tornheim, Jeffrey A; Brown, Diane M; Kruczynski, Kate; Hardick, Justin P; Sewell, Thelio; Jang, Minyoung; Church, Taylor; Walch, Samantha N; Reuland, Carolyn; Bachu, Vismaya S; Littlefield, Kirsten; Park, Han-Sol; Ursin, Rebecca L; Ganesan, Abhinaya; Kusemiju, Oyinkansola; Barnaba, Brittany; Charles, Curtisha; Prizzi, Michelle; Johnstone, Jaylynn R; Payton, Christine; Dai, Weiwei; Fuchs, Joelle; Massaccesi, Guido; Armstrong, Derek T; Townsend, Jennifer L; Keller, Sara C; Demko, Zoe O; Hu, Chen; Wang, Mei-Cheng; Sauer, Lauren M; Mostafa, Heba H; Keruly, Jeanne C; Mehta, Shruti H; Klein, Sabra L; Cox, Andrea L; Pekosz, Andrew; Heaney, Christopher D; Thomas, David L; Blair, Paul W; Manabe, Yukari C

BACKGROUND: Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate 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 mid-turbinate 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 RT-PCR, in 507 URT samples occurred a median (IQR) 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 one 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 (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m(2) (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). 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.