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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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.
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SciScore for 10.1101/2021.03.02.21252420: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study Cohort and Sampling: The Johns Hopkins University (JHU) School of Medicine Institutional Review Board approved this study.
Consent: Participants provided informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Laboratory Procedures: RT-PCR testing of study samples was performed on the Abbott m2000 platform (Abbott Molecular, Des Plaines, Il) in 600 µl volumes[9]. Abbottsuggested: (Abbott, RRID:SCR_010477)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to …
SciScore for 10.1101/2021.03.02.21252420: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Study Cohort and Sampling: The Johns Hopkins University (JHU) School of Medicine Institutional Review Board approved this study.
Consent: Participants provided informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Laboratory Procedures: RT-PCR testing of study samples was performed on the Abbott m2000 platform (Abbott Molecular, Des Plaines, Il) in 600 µl volumes[9]. Abbottsuggested: (Abbott, RRID:SCR_010477)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has limitations, including that it is under-sampled at the time of symptom onset and at > 1 month from symptom onset. We address this by including clinician-ordered samples outside of the study, but the time to viral RNA clearance may be less precisely described in participants whose study samples at 1-3 months remained positive than others. There was a non-significant trend towards immunocompromised host status being associated with viral RNA shedding duration, which may appear to contrast with reports of prolonged viral carriage in immunocompromised people[1-4]. This likely occurred because we grouped all immunocompromised people together, whereas there is probably a specific immunocompromised phenotype that leads to prolonged viral RNA detection. The associations of diabetes and COPD/asthma with faster time to viral RNA clearance were not found to be independent of other covariates in our sensitivity analysis (diabetes) or our second Cox model (COPD/asthma), and conflict with one report of asthma being associated with longer viral RNA shedding[39]. Larger studies are needed to determine whether diabetes, COPD, or asthma are associated with time to viral RNA clearance. In sum, we report viral and immune kinetics in an intensively characterized cohort of 95 adult outpatients with mild to moderate COVID-19. We demonstrate that elevated BMI, longer time to detection of oral SARS-CoV-2 IgG, and the absence of early fever are independently associated with longer time t...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04496466 Enrolling by invitation Clinical Characterization Protocol for Severe Infectious Dis… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
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