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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
Open Forum Infectious Diseases
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 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/m2 (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.
Antar AAR, Yu T, Pisanic N, Azamfirei R, Tornheim JA, Brown DM, Kruczynski K, Hardick JP, Sewell T, Jang M, Church T, Walch SN, Reuland C, Bachu VS, Littlefield K, Park HS, Ursin RL, Ganesan A, Kusemiju O, Barnaba B, Charles C, Prizzi M, Johnstone JR, Payton C, Dai W, Fuchs J, Massaccesi G, Armstrong DT, Townsend JL, Keller SC, Demko ZO, Hu C, Wang MC, Sauer LM, Mostafa HH, Keruly JC, Mehta SH, Klein SL, Cox AL, Pekosz A, Heaney CD, Thomas DL, Blair PW, Manabe YC. Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients. medRxiv [Preprint]. 2021 Mar 3:2021.03.02.21252420. doi: 10.1101/2021.03.02.21252420. Update in: Open Forum Infect Dis. 2021 Apr 16;8(6):ofab195. PMID: 33688688; PMCID: PMC7941665.