The utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis

Li, Xinwei; Xiong, Mengyuan; Deng, Qiaoling; Guo, Xia; Li, Yirong

doi:10.1002/jcla.24534

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…RAT performance did not significantly change between Omicron sublineages BA.2, BA.5 and XBB.1. This is aligned with current knowledge given that RATs target the nucleocapsid protein [21], while majority of mutations in SARS-CoV-2 variants of concern (VOC) occur in the spike protein [22]. These findings reassure us that the performance of RAT is not affected by the emergence of new variants and sublineages.…”

Section: Discussionsupporting

confidence: 74%

Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance

Tan,

Zeng,

Cui

et al. 2024

BMC Infect Dis

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Background While numerous studies have evaluated the real-world performance of rapid antigen tests (RATs), data on the effect of Omicron sublineages such as XBB and reinfections on RAT performance is limited. We assessed the performance of RATs and factors associated with RAT-negative results among individuals who tested SARS-CoV-2-positive by reverse transcription-polymerase chain reaction (RT-PCR). Methods We conducted a retrospective study among Singapore residents who underwent testing for SARS-CoV-2 with RAT (Acon Flowflex or SD Biosensor) and RT-PCR in the same clinical encounter between 9 May 2022 and 21 November 2022. RT-PCR served as a reference standard for RAT performance. Logistic regression was used to estimate the odds ratios (OR) of factors associated with negative RAT results among RT-PCR-positive cases. Results Of 8,620 clinical encounters analysed, 3,519 (40.8%) were SARS-CoV-2-positive on RT-PCR. Overall sensitivity and specificity of RAT was 84.6% (95% CI 83.3–85.7%) and 99.4% (95% CI 99.1–99.6%) respectively. Acon Flowflex consistently achieved higher sensitivity and specificity than SD Biosensor test kit. Among RT-PCR-positive cases, individuals who had a previous documented SARS-CoV-2 infection, coinfection with another respiratory pathogen or tested ≥ 6 days from symptom onset had higher odds of testing RAT-negative, but the associations were attenuated after adjustment for cycle threshold values (proxy for viral load). There was no significant difference in RAT performance between Omicron sublineages BA.2, BA.5 and XBB.1. Conclusion Diagnostic performance of RAT was not affected by changes in predominant circulating Omicron sublineages. However, reinfection cases may be under ascertained by RAT. In individuals with a previous SARS-CoV-2 infection episode or symptom onset ≥ 6 days prior to testing, a confirmatory RT-PCR may be considered if there is high clinical suspicion.

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Section: Discussionsupporting

confidence: 74%

Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance

Tan,

Zeng,

Cui

et al. 2024

BMC Infect Dis

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“…Despite the slow evolutionary changes that may affect the antigenic properties of the N protein, the majority of studies on the development of N-targeting diagnostics suggest that serum or plasma N levels may be used to detect SARS-CoV-2 and predict the COVID-19 outcome, and the specificity of such antigenic tests may reach 100% [ 91 ]. Thus, the ACTIV-3/TICO Group study revealed a strong positive correlation of pulmonary disease severity or exacerbation risks with plasma N levels, as well as an association of this indicator with the lack of anti-S antibodies, male sex and renal failure [ 92 ].…”

Section: Mutability Of N Sequences and Its Implication For The Perfor...mentioning

confidence: 99%

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Rak,

Isakova-Sivak,

Rudenko

2023

Vaccines

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The new SARS-CoV-2 coronavirus, which emerged in late 2019, is a highly variable causative agent of COVID-19, a contagious respiratory disease with potentially severe complications. Vaccination is considered the most effective measure to prevent the spread and complications of this infection. Spike (S) protein-based vaccines were very successful in preventing COVID-19 caused by the ancestral SARS-CoV-2 strain; however, their efficacy was significantly reduced when coronavirus variants antigenically different from the original strain emerged in circulation. This is due to the high variability of this major viral antigen caused by escape from the immunity caused by the infection or vaccination with spike-targeting vaccines. The nucleocapsid protein (N) is a much more conserved SARS-CoV-2 antigen than the spike protein and has therefore attracted the attention of scientists as a promising target for broad-spectrum vaccine development. Here, we summarized the current data on various N-based COVID-19 vaccines that have been tested in animal challenge models or clinical trials. Despite the high conservatism of the N protein, escape mutations gradually occurring in the N sequence can affect its protective properties. During the three years of the pandemic, at least 12 mutations have arisen in the N sequence, affecting more than 40 known immunogenic T-cell epitopes, so the antigenicity of the N protein of recent SARS-CoV-2 variants may be altered. This fact should be taken into account as a limitation in the development of cross-reactive vaccines based on N-protein.

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“…4 The nucleocapsid protein (N protein) is the most abundant protein antigen in SARS-CoV-2 and shows lower mutation rates among different variants compared to the spike protein. 5 As these features enable more sensitive measurements and a more reliable detection of different virus variants by the same antibodies, the N protein is commonly used as a target antigen in microtiter-plate enzyme-linked immunoassays (ELISA) and lateral flow immunoassays (LFA) intended for point-of-care testing. 6 Various other assay formats and detection schemes for the diagnosis of SARS-CoV-2 have been reviewed recently.…”

Section: Introductionmentioning

confidence: 99%

Digital and Analog Detection of SARS-CoV-2 Nucleocapsid Protein via an Upconversion-Linked Immunosorbent Assay

et al. 2023

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The COVID-19 crisis requires fast and highly sensitive tests for the early stage detection of the SARS-CoV-2 virus. For detecting the nucleocapsid protein (N protein), the most abundant viral antigen, we have employed upconversion nanoparticles that emit short-wavelength light under near-infrared excitation (976 nm). The anti-Stokes emission avoids autofluorescence and light scattering and thus enables measurements without optical background interference. The sandwich upconversion-linked immunosorbent assay (ULISA) can be operated both in a conventional analog mode and in a digital mode based on counting individual immune complexes. We have investigated how different antibody combinations affect the detection of the wildtype N protein and the detection of SARS-CoV-2 (alpha variant) in lysed culture fluid via the N protein. The ULISA yielded a limit of detection (LOD) of 1.3 pg/mL (27 fM) for N protein detection independent of the analog or digital readout, which is approximately 3 orders of magnitude more sensitive than conventional enzyme-linked immunosorbent assays or commercial lateral flow assays for home testing. In the case of SARS-CoV-2, the digital ULISA additionally improved the LOD by a factor of 10 compared to the analog readout.

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The utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis

Cited by 11 publications

References 44 publications

Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance

Diagnostic performance of rapid antigen tests (RAT) for COVID-19 and factors associated with RAT-negative results among RT-PCR-positive individuals during Omicron BA.2, BA.5 and XBB.1 predominance

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Digital and Analog Detection of SARS-CoV-2 Nucleocapsid Protein via an Upconversion-Linked Immunosorbent Assay

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