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Clin Chem . Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients

tetano

Editor, Senior Moderator
Clin Chem


. 2020 Sep 8;hvaa213.
doi: 10.1093/clinchem/hvaa213. Online ahead of print.
Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease


Alana F Ogata[SUP] 1 2 3 [/SUP], Adam M Maley[SUP] 1 2 3 [/SUP], Connie Wu[SUP] 1 2 3 [/SUP], Tal Gilboa[SUP] 1 2 3 [/SUP], Maia Norman[SUP] 1 2 4 [/SUP], Roey Lazarovits[SUP] 1 2 [/SUP], Chih-Ping Mao[SUP] 1 [/SUP], Gail Newton[SUP] 1 [/SUP], Matthew Chang[SUP] 5 [/SUP], Katrina Nguyen[SUP] 5 [/SUP], Maliwan Kamkaew[SUP] 5 [/SUP], Quan Zhu[SUP] 5 6 [/SUP], Travis E Gibson[SUP] 1 3 [/SUP], Edward T Ryan[SUP] 7 6 8 [/SUP], Richelle C Charles[SUP] 7 6 [/SUP], Wayne A Marasco[SUP] 5 6 [/SUP], David R Walt[SUP] 1 2 3 [/SUP]



Affiliations

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 coronavirus disease (COVID-19) patients. We studied plasma from 64 COVID-19 positive patients, 17 COVID-19 negative patients, and 34 pre-pandemic 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 COVID-19 patients. 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 one day) was statistically significant.
Conclusions: The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of COVID-19 positive patients 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.

Keywords: SARS-CoV-2; longitudinal plasma samples; serological; single molecule arrays; viral antigen.
 
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