Comparative analysis between STANDARD-E Covi-FERON ELISA with pre-existing IFN-γ release assays and determination of the optimum cutoff value for assessment of T-Cell response to SARS-CoV-2.

BACKGROUND: Interferon-gamma (IFN-γ) release assays (IGRAs) are useful for the assessment of the T-cell response to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). We aimed to assess the performance of the newly developed IGRA ELISA test compared to the pre-existing assays and to validate the cutoff value in real-world conditions. METHODS: We enrolled 219 participants and assessed agreement between STANDARD-E Covi-FERON ELISA with Quanti-FERON SARS-CoV-2 (QFN SARS-CoV-2), as well as with T SPOT Discovery SARS-CoV-2 based on Cohen's kappa-index. We further determined the optimal cutoff value for the Covi-FERON ELISA according to the immune response to vaccinations or infections. RESULTS: We found a moderate agreement between Covi-FERON ELISA and QFN SARS-CoV-2 before vaccination (kappa-index = 0.71), whereas a weak agreement after the first (kappa-index = 0.40) and second vaccinations (kappa-index = 0.46). However, the analysis between Covi-FERON ELISA and T SPOT assay demonstrated a strong agreement (kappa-index >0.7). The cut-off value of the OS (original spike) marker was 0.759 IU/mL with a sensitivity of 96.3% and specificity of 78.7%, and that of the variant spike (VS) marker was 0.663 IU/mL with a sensitivity and specificity of 77.8% and 80.6%, respectively. CONCLUSION: The newly determined cut-off value may provide an optimum value to minimize and prevent the occurrence of false-negative or false-positive during the assessment of T-cell immune response using Covi-FERON ELISA under real-world conditions.

Rapid Antigen Tests during the COVID-19 Era in Korea and Their Implementation as a Detection Tool for Other Infectious Diseases.

Rapid antigen tests (RATs) are diagnostic tools developed to specifically detect a certain protein of infectious agents (viruses, bacteria, or parasites). RATs are easily accessible due to their rapidity and simplicity. During the COVID-19 pandemic, RATs have been widely used in detecting the presence of the specific SARS-CoV-2 antigen in respiratory samples from suspected individuals. Here, the authors review the application of RATs as detection tools for COVID-19, particularly in Korea, as well as for several other infectious diseases. To address these issues, we present general knowledge on the design of RATs that adopt the lateral flow immunoassay for the detection of the analyte (antigen). The authors then discuss the clinical utilization of the authorized RATs amidst the battle against the COVID-19 pandemic in Korea and their role in comparison with other detection methods. We also discuss the implementation of RATs for other, non-COVID-19 infectious diseases, the challenges that may arise during the application, the limitations of RATs as clinical detection tools, as well as the possible problem solving for those challenges to maximize the performance of RATs and avoiding any misinterpretation of the test result.

Performance Evaluation of STANDARD Q COVID/FLU Ag Combo for Detection of SARS-CoV-2 and Influenza A/B.

We evaluated the performance of the STANDARD Q COVID/FLU Ag Combo test (Q Ag combo test) for the detection of SARS-CoV-2, influenza A, and influenza B using a single point-of-care device compared with real-time PCR. A total of 408 individuals, 55 positives with SARS-CoV-2, 90 with influenza A, 68 with influenza B, and 195 negatives for all viruses, participated. The Q Ag combo test demonstrated a high level of sensitivity of 92.73% and a specificity of 99.49% for the detection of SARS-CoV-2. When the number of days from symptom onset (DSO) was restricted to 0 < DSO ≤ 6, the sensitivity of the Q Ag combo test to detect SARS-CoV-2 was 100%, and when the Ct value of RdRp was ≤20, the sensitivity to detect SARS-CoV-2 was 93.10%. The Q Ag combo test results also demonstrated a sensitivity of 92.22% and a specificity of 100% for influenza A, a sensitivity of 91.18%, and a specificity of 99.49% for influenza B. The agreement analysis of the Q Ag combo test with the RT-PCR results demonstrated excellent outcomes, making it useful and efficient for the detection of SARS-CoV-2, influenza A, and influenza B.

Evaluation of the T cell and B cell response following the administration of COVID-19 vaccines in Korea.

BACKGROUND: The coronavirus disease (COVID-19) has been a worldwide concern since 2019. Vaccines are predicted to be crucial in preventing further outbreaks. The development and kinetics of immune responses determine the efficacy of COVID-19 vaccines. METHODS: We measured interferon-gamma (IFN-γ) levels upon administering homologous adenovirus vector-based (ChAdOx1-S [AZ], Ad26.COV2.S [JAN]), mRNA-based (BNT162b2 [PF]; mRNA-1273 [MO]), and heterologous (AZ/PF) vaccines in healthy Korean individuals using two IFN-γ release assays: the Covi-FERON ELISA and T-SPOT Discovery SARS-CoV-2 assay. B cell responses were evaluated by assessing the production of neutralizing antibodies by surrogate virus neutralization assay. The immune response among the vaccine groups was compared after adjusting the vaccination dose and interactions between each group. RESULTS: AZ triggered the highest T cell response after the first dose but showed instability after the second. PF and MO yielded stable and higher increments of T and B cell responses compared to AZ. MO yielded a higher immune response than PF. JAN yielded T and B cell responses at lower levels than the other vaccines. The booster dose triggered significant increases in the T and B cell responses and is therefore needed to protect against SARS-CoV-2 given the possibility of waning immune responses. CONCLUSION: Administering two doses of mRNA vaccines provides the most effective results among the administered vaccines in triggering the immune response specific to SARS-CoV-2 in healthy Korean individuals. Administration of booster doses demonstrated a significant increase in the immune response and may provide longer protection against SARS-CoV-2.

A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19).

Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies' efficacy and long-term viability. Studies reported several antibodies, that received authorization for COVID-19 treatment, are not effective against new variants or subvariants of SARS-CoV-2, hence their distribution has to be paused. Here, the authors reviewed the status of the currently available monoclonal antibodies for COVID-19 treatment, their potential as a therapeutic agent, and the challenges ahead. To address these issues, the authors presented general information on SARS-CoV-2 and how monoclonal antibodies work against SARS-CoV-2. The authors then focus on the antibodies that have been deployed for COVID-19 treatment and their current status, as well as the evidence supporting their potential as an early intervention against COVID-19. Lastly, the authors discussed some leading obstacles that hinder the development and administration of monoclonal antibodies for the treatment of COVID-19.

Evaluation of the T cell and B cell response following the administration of COVID-19 vaccines in Korea

Background The coronavirus disease (COVID-19) has been a worldwide concern since 2019. Vaccines are predicted to be crucial in preventing further outbreaks. The development and kinetics of immune responses determine the efficacy of COVID-19 vaccines. Methods We measured interferon-gamma (IFN-γ) levels upon administering homologous adenovirus vector-based (ChAdOx1-S [AZ], Ad26.COV2.S [JAN]), mRNA-based (BNT162b2 [PF];mRNA-1273 [MO]), and heterologous (AZ/PF) vaccines in healthy Korean individuals using two IFN-γ release assays: the Covi-FERON ELISA and T-SPOT Discovery SARS-CoV-2 assay. B cell responses were evaluated by assessing the production of neutralizing antibodies by surrogate virus neutralization assay. The immune response among the vaccine groups was compared after adjusting the vaccination dose and interactions between each group. Results AZ triggered the highest T cell response after the first dose but showed instability after the second. PF and MO yielded stable and higher increments of T and B cell responses compared to AZ. MO yielded a higher immune response than PF. JAN yielded T and B cell responses at lower levels than the other vaccines. The booster dose triggered significant increases in the T and B cell responses and is therefore needed to protect against SARS-CoV-2 given the possibility of waning immune responses. Conclusion Administering two doses of mRNA vaccines provides the most effective results among the administered vaccines in triggering the immune response specific to SARS-CoV-2 in healthy Korean individuals. Administration of booster doses demonstrated a significant increase in the immune response and may provide longer protection against SARS-CoV-2.

Performance evaluation of STANDARD Q COVID-19 Ag home test for the diagnosis of COVID-19 during early symptom onset.

BACKGROUND: Surveillance and control of SARS-CoV-2 outbreak through gold standard detection, that is, real-time polymerase chain reaction (RT-PCR), become a great obstacle, especially in overwhelming outbreaks. In this study, we aimed to analyze the performance of rapid antigen home test (RAHT) as an alternative detection method compared with RT-PCR. METHODS: In total, 79 COVID-19-positive and 217 COVID-19-negative patients confirmed by RT-PCR were enrolled in this study. A duration from symptom onset to COVID-19 confirmation of <5 days was considered a recruiting criterion for COVID-19-positive cases. A nasal cavity specimen was collected for the RAHT, and a nasopharyngeal swab specimen was collected for RT-PCR. RESULTS: Sensitivity of the STANDARD Q COVID-19 Ag Home Test (SD Biosensor, Korea), compared with RT-PCR, was 94.94% (75/79) (95% [confidence interval] CI, 87.54%-98.60%), and specificity was 100%. Sensitivity was significantly higher in symptomatic patients (98.00%) than in asymptomatic (89.66%) patients (p-value = 0.03). There was no difference in sensitivity according to the duration of symptom onset to confirmation (100% for 0-2 days and 96.97% for 3-5 days, respectively) (p-value = 1.00). The RAHT detected all 51 COVID-19 patients whose Ct values were ≤25 (100%), whereas sensitivity was 73.33% (11/15) among patients with Ct values >25 (p-value = 0.01). CONCLUSION: The RAHT showed an excellent sensitivity for COVID-19-confirmed cases, especially for those with symptoms. There was a decrease in sensitivity when the Ct value is over 25, indicating that RAHT screening may be useful during the early phase of symptom onset, when the viral numbers are higher and it is more transmissible.

Evaluation of the Diagnostic Accuracy of Nasal Cavity and Nasopharyngeal Swab Specimens for SARS-CoV-2 Detection via Rapid Antigen Test According to Specimen Collection Timing and Viral Load.

The rapid diagnosis of SARS-CoV-2 is an essential aspect in the detection and control of the spread of COVID-19. We evaluated the accuracy of the rapid antigen test (RAT) using samples from the nasal cavity and nasopharynx based on sample collection timing and viral load. We enrolled 175 patients, of which 71 patients and 104 patients had tested positive and negative, respectively, based on real time-PCR. Nasal cavity and nasopharyngeal swab samples were tested using STANDARD Q COVID-19 Ag tests (Q Ag, SD Biosensor, Korea). The sensitivity of the Q Ag test was 77.5% (95% confidence interval [CI], 67.8-87.2%) for the nasal cavity and 81.7% (95% [CI, 72.7-90.7%) for the nasopharyngeal specimens. The RAT results showed a substantial agreement between the nasal cavity and nasopharyngeal specimens (Cohen's kappa index = 0.78). The sensitivity of the RAT for nasal cavity specimens exceeded 89% for <5 days after symptom onset (DSO) and 86% for Ct of E and RdRp < 25. The Q Ag test performed fairly well, especially in the early DSO when a high viral load was present, and the nasal cavity swab can be considered an alternative site for the rapid diagnosis of COVID-19.