Direct detection of 4-dimensions of SARS-CoV-2: infection (vRNA), infectivity (antigen), binding antibody, and functional neutralizing antibody in saliva.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Saliva*/virology ; Saliva*/immunology ; SARS-CoV-2*/immunology ; SARS-CoV-2*/isolation & purification ; COVID-19*/immunology ; COVID-19*/diagnosis ; COVID-19*/virology ; Antibodies, Neutralizing*/immunology ; Antibodies, Neutralizing*/analysis ; RNA, Viral*/analysis ; Antibodies, Viral*/immunology ; Antibodies, Viral*/analysis; Humans ; Male ; Female ; Antigens, Viral/immunology ; Antigens, Viral/analysis ; Adult ; Middle Aged ; Sensitivity and Specificity ; Aged

Competing Interests: Declarations. Competing interests: O.Y. is the scientific advisory board for CytoDyn (stock options and cash) and board of directors for Applied Medical (stock and cash). D.W. is a consultant for AIONCO/Avellino and has stock options in AIONCO/Avellino. Other authors declared no conflict of interests.
We developed a 4-parameter clinical assay using Electric Field Induced Release and Measurement (EFIRM) technology to simultaneously assess SARS-CoV-2 RNA (vRNA), nucleocapsid antigen, host binding (BAb) and neutralizing antibody (NAb) levels from a drop of saliva with performance that equals or surpasses current EUA-approved tests. The vRNA and antigen assays achieved lower limit of detection (LOD) of 100 copies/reaction and 3.5 TCID₅₀/mL, respectively. The vRNA assay differentiated between acutely infected (n = 10) and infection-naïve patients (n = 33) with an AUC of 0.9818, sensitivity of 90%, and specificity of 100%. The antigen assay similarly differentiated these patient populations with an AUC of 1.000. The BAb assay detected BAbs with an LOD of 39 pg/mL and distinguished acutely infected (n = 35), vaccinated with prior infection (n = 13), and vaccinated infection-naïve patients (n = 13) from pre-pandemic (n = 81) with AUC of 0.9481, 1.000, and 0.9962, respectively. The NAb assay detected NAbs with a LOD of 31.6 Unit/mL and differentiated between COVID-19 recovered or vaccinated patients (n = 31) and pre-pandemic controls (n = 60) with an AUC 0.923, sensitivity of 87.10%, and specificity of 86.67%. Our combo assay represents a significant technological advancement to simultaneously address SARS-CoV-2 infection and immunity, and it lays the foundation for tackling potential future pandemics.
(© 2024. The Author(s).)

Update of: Res Sq. 2023 Dec 28:rs.3.rs-3745787. doi: 10.21203/rs.3.rs-3745787/v1. (PMID: 38234820)

Front Immunol. 2013 Aug 06;4:222. (PMID: 23964273)
Travel Med Infect Dis. 2021 Jan-Feb;39:101942. (PMID: 33278609)
Nucleic Acids Res. 2008 Jun;36(11):e65. (PMID: 18487624)
N Engl J Med. 2020 Sep 24;383(13):1283-1286. (PMID: 32857487)
PLoS One. 2021 Jul 1;16(7):e0251342. (PMID: 34197468)
JCI Insight. 2020 Oct 2;5(19):. (PMID: 32870820)
BMC Infect Dis. 2018 Dec 29;18(1):707. (PMID: 30594124)
J Clin Virol. 2021 Apr;137:104782. (PMID: 33711691)
Biosens Bioelectron. 2020 Oct 1;165:112454. (PMID: 32729549)
Open Med (Wars). 2021 May 11;16(1):749-753. (PMID: 34013047)
Viruses. 2021 Jul 14;13(7):. (PMID: 34372570)
Cell. 2021 Feb 18;184(4):861-880. (PMID: 33497610)
Am J Respir Crit Care Med. 2014 Nov 15;190(10):1117-26. (PMID: 25317990)
Front Oncol. 2020 Jul 24;10:1240. (PMID: 32793495)
Clin Cancer Res. 2009 Jul 1;15(13):4446-52. (PMID: 19509137)
Sci Transl Med. 2021 Jan 20;13(577):. (PMID: 33288662)
Nat Commun. 2020 Sep 11;11(1):4541. (PMID: 32917884)
Oman Med J. 2021 Sep 30;36(5):e297. (PMID: 34631156)
Clin Chem. 2021 Nov 1;67(11):1545-1553. (PMID: 34240163)
J Clin Med. 2021 Jan 17;10(2):. (PMID: 33477365)
J Mol Diagn. 2020 Aug;22(8):1050-1062. (PMID: 32497715)
Nat Biotechnol. 2020 Sep;38(9):1073-1078. (PMID: 32704169)
Nat Microbiol. 2022 May;7(5):640-652. (PMID: 35484231)
Nat Biomed Eng. 2022 Aug;6(8):968-978. (PMID: 35941191)
J Immunol. 2022 Feb 15;208(4):819-826. (PMID: 35039333)
Nat Med. 2021 Jul;27(7):1205-1211. (PMID: 34002089)
Diagnostics (Basel). 2021 Sep 24;11(10):. (PMID: 34679455)
Brief Bioinform. 2012 Jan;13(1):83-97. (PMID: 21422066)
Biosens Bioelectron. 2013 Jun 15;44:115-21. (PMID: 23402739)
J Infect. 2020 Jul;81(1):e45-e50. (PMID: 32298676)
Science. 2020 Mar 27;367(6485):1444-1448. (PMID: 32132184)
J Med Virol. 2023 Feb;95(2):e28568. (PMID: 36756925)
J Mol Diagn. 2018 Nov;20(6):738-742. (PMID: 30309763)
Biotechniques. 2020 Sep;69(3):178-185. (PMID: 32635743)
Nat Rev Microbiol. 2023 Mar;21(3):133-146. (PMID: 36639608)
EBioMedicine. 2020 Dec;62:103101. (PMID: 33160207)
Cancers (Basel). 2020 Jul 24;12(8):. (PMID: 32722209)

U18 TR003778 United States TR NCATS NIH HHS; U54 HL119893 United States HL NHLBI NIH HHS; U18 TR003778, U54 HL119893 United States TR NCATS NIH HHS

0 (Antibodies, Neutralizing)
0 (RNA, Viral)
0 (Antibodies, Viral)
0 (Antigens, Viral)

Date Created: 20241227 Date Completed: 20241227 Latest Revision: 20250107

20250114

PMC11681011

10.1038/s41598-024-81019-4

39730575