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

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 BarnabaCurtisha 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	ofab195
Journal	Open Forum Infectious Diseases
Volume	8
Issue number	6
DOIs	https://doi.org/10.1093/ofid/ofab195
State	Published - Jun 1 2021

Keywords

COVID-19
RT-PCR
SARS-CoV-2
antibody
viral RNA

ASJC Scopus subject areas

Oncology
Infectious Diseases

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10.1093/ofid/ofab195

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Antar, A. A. R., Yu, T., Pisanic, N., Azamfirei, R., Tornheim, J. A., Brown, D. M., Kruczynski, K., Hardick, J. P., Sewell, T., Jang, M., Church, T., Walch, S. N., Reuland, C., Bachu, V. S., Littlefield, K., Park, H. S., Ursin, R. L., Ganesan, A., Kusemiju, O., ... Manabe, Y. C. (2021). 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, 8(6), Article ofab195. https://doi.org/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. / Antar, Annukka A.R.; Yu, Tong; Pisanic, Nora et al.
In: Open Forum Infectious Diseases, Vol. 8, No. 6, ofab195, 01.06.2021.

Research output: Contribution to journal › Article › peer-review

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 2021, '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, vol. 8, no. 6, ofab195. https://doi.org/10.1093/ofid/ofab195

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title = "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",

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",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2021",

month = jun,

day = "1",

doi = "10.1093/ofid/ofab195",

language = "English (US)",

volume = "8",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - 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

AU - Antar, Annukka A.R.

AU - Yu, Tong

AU - Pisanic, Nora

AU - Azamfirei, Razvan

AU - Tornheim, Jeffrey A.

AU - Brown, Diane M.

AU - Kruczynski, Kate

AU - Hardick, Justin P.

AU - Sewell, Thelio

AU - Jang, Minyoung

AU - Church, Taylor

AU - Walch, Samantha N.

AU - Reuland, Carolyn

AU - Bachu, Vismaya S.

AU - Littlefield, Kirsten

AU - Park, Han Sol

AU - Ursin, Rebecca L.

AU - Ganesan, Abhinaya

AU - Kusemiju, Oyinkansola

AU - Barnaba, Brittany

AU - Charles, Curtisha

AU - Prizzi, Michelle

AU - Johnstone, Jaylynn R.

AU - Payton, Christine

AU - Dai, Weiwei

AU - Fuchs, Joelle

AU - Massaccesi, Guido

AU - Armstrong, Derek T.

AU - Townsend, Jennifer L.

AU - Keller, Sara C.

AU - Demko, Zoe O.

AU - Hu, Chen

AU - Wang, Mei Cheng

AU - Sauer, Lauren M.

AU - Mostafa, Heba H.

AU - Keruly, Jeanne C.

AU - Mehta, Shruti H.

AU - Klein, Sabra L.

AU - Cox, Andrea L.

AU - Pekosz, Andrew

AU - Heaney, Christopher D.

AU - Thomas, David L.

AU - Blair, Paul W.

AU - Manabe, Yukari C.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - RT-PCR

KW - SARS-CoV-2

KW - antibody

KW - viral RNA

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UR - http://www.scopus.com/inward/citedby.url?scp=85118521117&partnerID=8YFLogxK

U2 - 10.1093/ofid/ofab195

DO - 10.1093/ofid/ofab195

M3 - Article

C2 - 34095338

AN - SCOPUS:85118521117

SN - 2328-8957

VL - 8

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

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ER -

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

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