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  • Frontiers Media SA  (17)
  • 1
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    Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-4-14)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-4-14)
    Abstract: For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND 50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND 50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2022.822599
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 2
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-7-11)
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    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-7-11)
    Abstract: With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND 50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND 50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND 50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2022.948014
    DOI: 10.3389/fcimb.2022.948014.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 3
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    Neutralizing activity against Omicron BA.5 after tixagevimab/cilgavimab administration comparable to those after Omicron BA.1/BA.2 breakthrough infections
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-2)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-2)
    Abstract: The effect of tixagevimab/cilgavimab (Evusheld™; AstraZeneca, UK) should be evaluated in the context of concurrent outbreak situations. Methods For serologic investigation of tixagevimab/cilgavimab during the BA.5 outbreak period, sera of immunocompromised (IC) hosts sampled before and one month after tixagevimab/cilgavimab administration and those of healthcare workers (HCWs) sampled one month after a 3 rd shot of COVID-19 vaccines, five months after BA.1/BA.2 breakthrough infection (BI), and one month after BA.5 BI were investigated. Semi-quantitative anti-spike protein antibody (Sab) test and plaque reduction neutralizing test (PRNT) against BA.5 were performed. Results A total of 19 IC hosts (five received tixagevimab/cilgavimab 300 mg and 14 received 600 mg) and 41 HCWs (21 experienced BA.1/BA.2 BI and 20 experienced BA.5 BI) were evaluated. Baseline characteristics did not differ significantly between IC hosts and HCWs except for age and hypertension. Sab significantly increased after tixagevimab/cilgavimab administration (median 130.2 BAU/mL before tixagevimab/cilgavimab, 5,665.8 BAU/mL after 300 mg, and 10,217 BAU/mL after 600 mg; both P & lt; 0.001). Sab of one month after the 3 rd shot (12,144.2 BAU/mL) or five months after BA.1/BA.2 BI (10,455.8 BAU/mL) were comparable with that of tixagevimab/cilgavimab 600 mg, while Sab of one month after BA.5 BI were significantly higher (22,216.0 BAU/mL; P & lt; 0.001). BA.5 PRNT ND 50 significantly increased after tixagevimab/cilgavimab administration (median ND 50 29.6 before tixagevimab/cilgavimab, 170.8 after 300 mg, and 298.5 after 600 mg; both P & lt; 0.001). The ND 50 after tixagevimab/cilgavimab 600 mg was comparable to those of five months after BA.1 BI (ND 50 200.9) while ND 50 of one month after the 3 rd shot was significantly lower (ND 50 107.6; P = 0.019). The ND 50 of one month after BA.5 BI (ND 50 1,272.5) was highest among tested groups, but statistical difference was not noticed with tixagevimab/cilgavimab 600 mg. Conclusion Tixagevimab/cilgavimab provided a comparable neutralizing activity against the BA.5 with a healthy adult population who were vaccinated with a 3 rd shot and experienced BA.1/BA.2 BI.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2023.1139980
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 4
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    Table_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-8-22)
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    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-8-22)
    Abstract: Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p & lt; 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55–3.19; p & lt; 0.001) and for bacteremia (OR 5.18, 95% CI 3.13–8.56; p & lt; 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67–6.54; p & lt; 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.954114
    DOI: 10.3389/fmed.2022.954114.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 5
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    Image_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-10-12)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-12)
    Abstract: The impact of nirmatrelvir/ritonavir treatment on shedding of viable virus in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Methods A prospective cohort study evaluating mildly ill COVID-19 patients was conducted. Virologic responses were compared between nirmatrelvir/ritonavir-treatment and supportive care groups. Risk factors and relevant clinical factors for shedding of viable virus were investigated. Results A total of 80 COVID-19 patients were enrolled and 222 sputum specimens were collected. Ten patients were dropped during follow-up, and 33 patients in the nirmatrelvir/ritonavir and 37 in the supportive care groups were compared. The median age was 67 years, and 67% were male. Clinical characteristics were similar between groups. Viral loads decreased significantly faster in the nirmatrelvir/ritonavir group compared with the supportive care group ( P & lt; 0.001), and the slope was significantly steeper (–2.99 ± 1.54 vs. –1.44 ± 1.52; P & lt; 0.001). The duration of viable virus shedding was not statistically different between groups. In the multivariable analyses evaluating all collected specimens, male gender (OR 2.51, 95% CI 1.25–5.03, P = 0.010), symptom score (OR 1.41, 95% CI 1.07–1.87, P = 0.015), days from symptom onset (OR 0.72, 95% CI 0.59–0.88, P = 0.002), complete vaccination (OR 0.09, 95% CI 0.01–0.87, P = 0.038), and BA.2 subtype (OR 0.49, 95% CI 0.26–0.91, P = 0.025) were independently associated with viable viral shedding, while nirmatrelvir/ritonavir treatment was not. Conclusion Nirmatrelvir/ritonavir treatment effectively reduced viral loads of SARS-CoV-2 Omicron variants but did not decrease the duration of viable virus shedding.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.988559
    DOI: 10.3389/fmed.2022.988559.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 6
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    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-9-22)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-9-22)
    Abstract: The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20–71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0–18.0) compared to those in the ChAd group (median 23.0, IQR 8.0–43.0, P =0.012) but similar to that in the BNT group (median 5.0, IQR 3.0–9.0, P =0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P =0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P =0.002) and BNT (1.656 ± 1.925 IU/mL, P =0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.744206
    DOI: 10.3389/fimmu.2021.744206.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 7
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    Serologic Evaluation of Healthcare Workers Caring for COVID-19 Patients in the Republic of Korea
    Frontiers Media SA ; 2020
    In:  Frontiers in Microbiology Vol. 11 ( 2020-11-20)
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    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 11 ( 2020-11-20)
    Abstract: The safety of healthcare workers (HCWs) against severe acute respiratory syndrome virus 2 (SARS-CoV-2) transmission is an important aspect of managing the coronavirus disease 2019 (COVID-19) pandemic. In the South Korea, highly stringent infection prevention and control (IPC) guidelines are implemented, and reports of healthcare-associated SARS-CoV-2 transmission among HCWs are limited. However, subclinical infections may have been missed by the current symptom-based screening strategy. To evaluate the risk of undetected SARS-CoV-2 transmissions from COVID-19 patients to HCWs, we conducted a multicenter seroprevalence study after the first surge of the COVID-19 outbreak. A total of 432 HCWs were evaluated, comprising 309 HCWs designated to laboratory-confirmed COVID-19 patient care and 123 non-designated HCWs. Designated HCWs wore personal protective equipment including an N95 respirator, eye protection, hooded overalls, shoe covers, and inner and outer gloves. Use of a powered air-purifying respirator was recommended for aerosol-generating procedures or long-duration care activities. A high-sensitivity (99.1%) fluorescence immunoassay immunoglobulin G (IgG) kit was used as the initial screening test, and two enzyme-linked immunosorbent assay kits for total and IgG antibodies were used to confirm the test results. A microneutralization test was additionally performed to evaluate the neutralizing activity of positive specimens. Among the evaluated HCWs, none of the non-designated HCWs had a positive result, while one of the HCWs designated for COVID-19 patient care (1/309, 0.3%) was seropositive for SARS-CoV-2 with confirmed neutralizing activity (1:40). This finding suggests that subclinical seroconversion may occur among HCWs caring for COVID-19 patients, although the risk is low under strict IPC guidance.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2020.587613
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587354-4
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  • 8
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-11-23)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-23)
    Abstract: To evaluate clinical effectiveness of regdanvimab, a monoclonal antibody agent for treating coronavirus 2019 (COVID-19). Methods A retrospective cohort study was conducted at two general hospitals during the study period of December 2020 to May 2021. Mild COVID-19 patients with risk factors for disease progression admitted to the hospitals within seven days of symptom onset were enrolled and followed until discharge or referral. Multivariate analyses for disease progression were conducted in the total and propensity score (PS)-matched cohorts. Results A total of 778 mild COVID-19 patients were included and classified as the regdanvimab (n = 234) and supportive care (n = 544) groups. Significantly fewer patients required O 2 supplementation via nasal prong in the regdanvimab group (8.1%) than in the supportive care group (18.4%, P & lt; 0.001). The decreased risk for O 2 support by regdanvimab treatment was noticed in the multivariate analysis of the total cohort (HR 0.570, 95% CI 0.343–0.946, P = 0.030), but it was not statistically significant in the PS-matched cohort ( P = 0.057). Progression to severe disease was also significantly lower in the regdanvimab group (2.1%) than in the supportive care group (9.6%, P & lt; 0.001). The significantly reduced risk for progression to severe disease by regdanvimab treatment was observed in the analysis of both the total cohort (HR 0.262, 95% CI 0.103–0.667, P = 0.005) and PS-matched cohort (HR 0.176, 95% CI 0.060–0.516, P = 0.002). Potential risk factors for progression were investigated in the supportive care group and SpO 2 & lt; 97% and CRP elevation & gt;1.5 mg/dL were common risk factors for O 2 support and progression to severe disease. Among the patients with any of these factors, regdanvimab treatment was associated with decreased risk for progression to severe disease with slightly lower HR (HR 0.202, 95% CI 0.062–0.657, P = 0.008) than that of the total cohort. Conclusion Regdanvimab treatment was associated with a decreased risk of progression to severe disease.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.772320
    DOI: 10.3389/fimmu.2021.772320.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 9
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-9-23)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-23)
    Abstract: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy. Methods We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND 50 ) against wild type (WT) SARS-CoV-2 and that of the Delta variant. Results We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND 50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%; P & lt; 0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT). Conclusion Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.968105
    DOI: 10.3389/fimmu.2022.968105.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 10
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    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Cellular and Infection Microbiology Vol. 13 ( 2023-5-15)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 13 ( 2023-5-15)
    Abstract: Immune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated. Methods A nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O 2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant–confirmed patients. Results A total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O 2 support (18.4% vs. 27.1%, P & lt; 0.001) and progressed to severe disease (4.0% vs. 8.0%, P & lt; 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O 2 support (HR 0.677, 95% CI 0.561–0.816) and progression to severe disease (HR 0.489, 95% CI 0.337–0.709). Among the 939 delta-confirmed patients, O 2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O 2 support (HR 0.963, 95% CI 0.697–1.329) or progression to severe disease (HR 0.665, 95% CI 0.349–1.268) in delta-confirmed group. Conclusions Regdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2023.1192512
    DOI: 10.3389/fcimb.2023.1192512.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2619676-1
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