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Delayed detection of oral fluid anti-SARS-CoV-2 antibodies increases the time to viral clearance

A prospective observational study recently conducted at Johns Hopkins University, USA, has revealed that late appearance of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in oral fluid, absence of fever as an early symptom, and elevated body mass index (BMI) are associated with delayed clearance of viral RNA in mild to moderate coronavirus disease 2019 (COVID-19) patients. The study is currently available on the medRxiv* preprint server.

Study: 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. Image Credit: ktsdesign / Shutterstock


SARS-CoV-2, the causative pathogen of the COVID-19 pandemic, is an enveloped RNA betacoronavirus of the Coronaviridae family. Because of the significant involvement in viral entry, the spike glycoprotein of SARS-CoV-2 is the most potent target of both binding and neutralizing antibodies developed specifically against it. The majority of studies investigating host humoral immune responses to SARS-CoV-2 have highlighted the differences in antibody kinetics between mild or asymptomatic and severe COVID-19 patients.

There is evidence suggesting that mildly affected COVID-19 patients mostly exhibit lower levels of SARS-CoV-2 specific neutralizing antibodies in sera. Moreover, studies have shown that lower titers of SARS-CoV-2 specific antibodies and lower numbers of B and T cells in the blood are associated with prolonged shedding of viral RNA.

In the current study, the scientists have explored the correlation between antibody response and viral shedding in mildly or moderately affected COVID-19 patients.

Study design

A total of 95 COVID-19 patients participated in the study. The patients collected mid-turbinate nasal and oropharyngeal swabs and oral fluids by themselves at home during the initial 14 days of the study. In addition, nasopharyngeal swabs were collected from 53 out of 95 patients in a research clinic an average of 45 days after the commencement of the study. The collection of the samples was initiated (study day 0) an average of 9 days after the symptom onset.   

Important observations

By conducting real-time polymerase chain reaction reverse transcription (RT-PCR) testing of longitudinally collected upper respiratory tract samples (nasal-oropharyngeal and nasopharyngeal swabs and oral fluid), the scientists observed that the viral load was maximum before and just after the onset of COVID-19 symptoms. They cultured 183 samples for the virus and observed that 16 samples collected from 14 participants were positive for SARS-CoV-2. In these 14 participants, the virus culture positive samples were detected up to 11 days after the onset of symptoms, which is one day longer than the recommended isolation period.

Interestingly, the scientists observed an independent correlation between the delayed appearance of anti- SARS-CoV-2 antibodies in the oral fluid and prolonged viral shedding. Moreover, they observed that the possibility of having negative viral culture results from nasal swabs could be predicted by the presence of anti- SARS-CoV-2 antibodies in the oral fluid. The association between oral fluid antibody and viral culture status was observed even in samples with high viral load. With further analysis, they observed that the duration between the symptom onset and first detection of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies in the oral fluid was 9 – 11 days. Overall, these findings indicate that mild to moderate COVID-19 patients who display SARS-CoV-2 specific antibodies in the oral fluid are less likely to transmit the infection to others.

Regarding other determinants of viral clearance, the scientists observed that COVID-19 patients with BMI more than 25 kg/m2 exhibited longer viral RNA clearance time. Interestingly, they did not observe any impact of hypertension and diabetes on the association between BMI and time to viral RNA clearance.

The presence of asthma or chronic obstructive pulmonary disease, diabetes, and fever as an early COVID-19 symptom showed an independent association with faster clearance of viral RNA. Moreover, a trend of prolonged viral shedding was observed in immunocompromised COVID-19 patients. Interestingly, no association was observed between the titers of anti- SARS-CoV-2 antibodies in convalescent plasma samples and the time to viral clearance.

Study significance

The study findings reveal that elevated BMI, absence of fever as one of the early COVID-19 symptoms, and delayed appearance of anti- SARS-CoV-2 antibodies in the oral fluid are independently associated with prolonged viral shedding in mild to moderate COVID-19 patients. The study also highlights that early detection of antibodies in the oral fluid reduces the risk of disease transmission.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Antar AAR. 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. MedRxiv. doi:,

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Tags: Antibodies, Antibody, Asthma, Blood, Body Mass Index, Chronic, Chronic Obstructive Pulmonary Disease, Convalescent Plasma, Coronavirus, Coronavirus Disease COVID-19, Diabetes, Fever, Glycoprotein, Pandemic, Pathogen, Polymerase, Polymerase Chain Reaction, Receptor, Research, Respiratory, RNA, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Transcription, Virus

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Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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