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
medRxiv. 2021 Mar 3:2021.03.02.21252420. doi: 10.1101/2021.03.02.21252420.
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.
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.
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 (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).
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.
在轻度至中度新型冠状病毒肺炎（COVID-19）患者的上呼吸道（URT）中持续检测到严重急性呼吸综合征冠状病毒2（SARS-CoV-2）RNA的情况很常见。我们试图确定SARS-CoV-2 RNA检测持续时间的宿主和免疫决定因素。
95名门诊患者在家中和研究诊所自行采集中鼻甲鼻拭子、口咽（OP）拭子和龈沟液（口腔液）样本，在1至3个月内平均采集6次。对样本进行病毒RNA、病毒培养以及SARS-CoV-2和其他人类冠状病毒抗体检测，并使用Cox比例风险模型估计相关性。
通过SARS-CoV-2逆转录聚合酶链反应（RT-PCR）检测，507份URT样本中的病毒RNA清除时间中位数（IQR）为症状出现后33.5（17 - 63.5）天。在183份RT-PCR阳性样本中，症状出现后2至11天采集的16份鼻-OP样本病毒培养呈阳性。除一名病毒培养阳性参与者外，所有参与者的口腔液抗SARS-CoV-2抗体均为阴性。口腔液中首次检测到抗体的平均时间为症状出现后8至13天。口腔液抗SARS-CoV-2 S抗体首次检测时间较长（调整后风险比[aHR]0.96，95%置信区间[CI]0.92 - 0.99，p = 0.020）以及体重指数（BMI）≥25kg/m²（aHR 0.37，95%CI 0.18 - 0.78，p = 0.009）与SARS-CoV-2病毒RNA清除时间较长独立相关。发热作为COVID-19最初的三个症状之一与病毒RNA清除时间较短相关（aHR 2.06，95%CI 1.02 - 4.18，p = 0.044）。
我们证明，口腔液中SARS-CoV-2特异性抗体出现延迟、BMI升高以及早期无发热与URT病毒RNA清除延迟独立相关。
