Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease
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Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression.
Methods
We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of patients with coronavirus disease (COVID-19). We studied plasma from 64 patients who were COVID-19 positive, 17 who were COVID-19 negative, and 34 prepandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 patients with COVID-19. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes.
Results
SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95% CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral-antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within 1 day) was statistically significant.
Conclusions
The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of patients who were COVID-19 positive to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.
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SciScore for 10.1101/2020.04.14.20065771: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 Search strategy and selection criteria: We conducted searches of the PubMed database on March 20, 2020 using the search term “coronavirus” and each of the following terms or phrases: “serolog*”, “serop*”, “cross reactivity”, and “complement fixation”. PubMedsuggested: (PubMed, RRID:SCR_004846)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of systematic …
SciScore for 10.1101/2020.04.14.20065771: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 Search strategy and selection criteria: We conducted searches of the PubMed database on March 20, 2020 using the search term “coronavirus” and each of the following terms or phrases: “serolog*”, “serop*”, “cross reactivity”, and “complement fixation”. PubMedsuggested: (PubMed, RRID:SCR_004846)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of systematic review: We have suggested a set of search terms to identify relevant work, and others may expand on this search. Due to the speed of new research being produced, we limited our systematic review of SARS-CoV-2 papers to before March 20, 2020. Further evidence on immune responses to SARS-CoV-2 is likely contained in work that has since been published. We excluded from the review animal studies and studies of animal CoVs to remain human-focused, but this literature is likely relevant to some areas of the review. We limited the scope of the review to antibody-mediated immunity, meaning that understanding of some areas of the review may be incomplete. Finally, digitized data could be affected by publication bias or other selection bias, meaning that it might not be representative of data from all studies. The aim of the pooled analyses was to summarize the array of studies rather than formally explore hypotheses, and as a result the models used are simple. For example, in estimating force of infection from age-stratified seroprevalence data, we did not consider other features of a model such as assay sensitivity, time- and age-varying force of infections, seroreversion, and cross-reactivity between strains, that might better explain patterns seen in the data. Implications for SARS-CoV-2 pandemic responses and future outlooks:
Results from TrialIdentifier: No clinical trial numbers were referenced.
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.
- No protocol registration statement was detected.
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