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

doi:10.1093/ofid/ofab195

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 Infect Dis. 2021 Apr 16;8(6):ofab195. doi: 10.1093/ofid/ofab195. eCollection 2021 Jun.

Authors

Annukka A R Antar¹, Tong Yu¹, Nora Pisanic², Razvan Azamfirei¹, Jeffrey A Tornheim¹, Diane M Brown¹, Kate Kruczynski², Justin P Hardick¹, Thelio Sewell¹, Minyoung Jang¹, Taylor Church¹, Samantha N Walch¹, Carolyn Reuland¹, Vismaya S Bachu¹, Kirsten Littlefield³, Han-Sol Park³, Rebecca L Ursin⁴, Abhinaya Ganesan³, Oyinkansola Kusemiju¹, Brittany Barnaba¹, Curtisha Charles¹, Michelle Prizzi¹, Jaylynn R Johnstone¹, Christine Payton¹, Weiwei Dai¹, Joelle Fuchs¹, Guido Massaccesi¹, Derek T Armstrong⁵, Jennifer L Townsend¹, Sara C Keller¹, Zoe O Demko¹, Chen Hu⁶, Mei-Cheng Wang⁷, Lauren M Sauer⁸, Heba H Mostafa⁴, Jeanne C Keruly¹, Shruti H Mehta⁹, Sabra L Klein^{3

4}, Andrea L Cox^{1

3

6}, Andrew Pekosz³, Christopher D Heaney^{2

9

10}, David L Thomas¹, Paul W Blair¹, Yukari C Manabe^{1

3}

Affiliations

¹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
³ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁴ Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁸ Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹⁰ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

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.

Abstract

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