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ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19.

ABSTRACT: A serological immunoassay based on enzyme-linked immunosorbent assay (ELISA) is a crucial tool for screening and identification of human SARS-CoV-2 seroconversion. Various immunoassays are developed to detect the spike 1 (S1) and nucleocapsid (NP) proteins of SARS-CoV-2; however, these serological tests have low sensitivity. Here, a novel microplate (MP) is developed on which a ZnO nanowire (NW) is fabricated by a modified hydrothermal synthesis method. This plate is coated with SARS-CoV-2 NP and used as a fluorescent immunoassay (FIA) to detect antibodies specific for SARS-CoV-2 NP. Compared with the bare MP, the ZnO-NW MP binds high levels (up to 5 µg mL^-1) of SARS-CoV-2 NP tagged to histidine without any surface treatment. A novel serological assay based on the ZnO-NW MP is more sensitive than a commercial immunoassay, enabling early detection (within <5 days of a reverse transcription polymerase chain reaction-confirmed COVID-19 infection) of anti-SARS-CoV-2 NP IgG antibodies in asymptomatic patients with COVID-19. This is the first assay to detect early antibody responses to SARS-CoV-2 in asymptomatic patients. Therefore, this serological assay will facilitate accurate diagnosis of COVID-19, as well as estimation of COVID-19 prevalence and incidence.

SUBMITTER: Kim J

PROVIDER: S-EPMC9073923 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19.

Kim Jung J Lee Sung Kyun SK Lee Jong-Hwan JH Kim Hye-Yeon HY Kim Nam Hoon NH Lee Chang Hoon CH Lee Chang-Seop CS Kim Hong Gi HG

Advanced materials interfaces 20220205 14

A serological immunoassay based on enzyme-linked immunosorbent assay (ELISA) is a crucial tool for screening and identification of human SARS-CoV-2 seroconversion. Various immunoassays are developed to detect the spike 1 (S1) and nucleocapsid (NP) proteins of SARS-CoV-2; however, these serological tests have low sensitivity. Here, a novel microplate (MP) is developed on which a ZnO nanowire (NW) is fabricated by a modified hydrothermal synthesis method. This plate is coated with SARS-CoV-2 NP an ...[more]

PMID: 35538927

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Project description:BackgroundThe missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.MeasureUtilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.ResultsA combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.ConclusionOur findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

Project description:ImportanceEasy-to-administer antiviral treatments may be used to prevent progression from asymptomatic infection to COVID-19 and to reduce viral carriage.ObjectiveEvaluate the efficacy and safety of subcutaneous casirivimab and imdevimab antibody combination (REGEN-COV) to prevent progression from early asymptomatic SARS-CoV-2 infection to COVID-19.DesignRandomized, double-blind, placebo-controlled, phase 3 study that enrolled asymptomatic close contacts living with a SARS-CoV-2-infected household member (index case). Participants who were SARS-CoV-2 RT-qPCR-positive at baseline were included in the analysis reported here.SettingMulticenter trial conducted at 112 sites in the United States, Romania, and Moldova.ParticipantsAsymptomatic individuals ≥12 years of age were eligible if identified within 96 hours of collection of the index case's positive SARS-CoV-2 test sample.InterventionsA total of 314 asymptomatic, SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact were randomized 1:1 to receive a single dose of subcutaneous REGEN-COV 1200mg (n=158) or placebo (n=156).Main outcomes and measuresThe primary endpoint was the proportion of participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy endpoints were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Safety was assessed in all treated participants.ResultsSubcutaneous REGEN-COV 1200mg significantly prevented progression from asymptomatic to symptomatic disease compared with placebo (31.5% relative risk reduction; 29/100 [29.0%] vs 44/104 [42.3%], respectively; P=.0380). REGEN-COV reduced the overall population burden of high-viral load weeks (39.7% reduction vs placebo; 48 vs 82 total weeks; P=.0010) and of symptomatic weeks (45.3% reduction vs placebo; 89.6 vs 170.3 total weeks; P=.0273), the latter corresponding to an approximately 5.6-day reduction in symptom duration per symptomatic participant. Six placebo-treated participants had a COVID-19-related hospitalization or ER visit versus none for those receiving REGEN-COV. The proportion of participants receiving placebo who had ≥1 treatment-emergent adverse events was 48.1% compared with 33.5% for those receiving REGEN-COV, including events related (39.7% vs 25.8%, respectively) or not related (16.0% vs 11.0%, respectively) to COVID-19.Conclusions and relevanceSubcutaneous REGEN-COV 1200mg prevented progression from asymptomatic SARS-CoV-2 infection to COVID-19, reduced the duration of high viral load and symptoms, and was well tolerated.Trial registrationClinicalTrials.gov Identifier, NCT04452318.

Dataset Information

ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19.

Publications

ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19.

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