SARS-CoV-2 Neutralizing Responses in Various Populations, at the Time of SARS-CoV-2 Variant Virus Emergence: Evaluation of Two Surrogate Neutralization Assays in Front of Whole Virus Neutralization Test

The SARS-CoV-2 neutralizing antibodies response is the best indicator of effective protection after infection and/or vaccination, but its evaluation requires tedious cell-based experiments using an infectious virus. We analyzed, in 105 patients with various histories of SARS-CoV-2 infection and/or vaccination, the neutralizing response using a virus neutralization test (VNT) against B.1, Alpha, Beta and Omicron variants, and compared the results with two surrogate assays based on antibody-mediated blockage of the ACE2-RBD interaction (Lateral Flow Boditech and ELISA Genscript). The strongest response was observed for recovered COVID-19 patients receiving one vaccine dose. Naïve patients receiving 2 doses of mRNA vaccine also demonstrate high neutralization titers against B.1, Alpha and Beta variants, but only 34.3% displayed a neutralization activity against the Omicron variant. On the other hand, non-infected patients with half vaccination schedules displayed a weak and inconstant activity against all isolates. Non-vaccinated COVID-19 patients kept a neutralizing activity against B.1 and Alpha up to 12 months after recovery but a decreased activity against Beta and Omicron. Both surrogate assays displayed a good correlation with the VNT. However, an adaptation of the cut-off positivity was necessary, especially for the most resistant Beta and Omicron variants. We validated two simple and reliable surrogate neutralization assays, which may favorably replace cell-based methods, allowing functional analysis on a larger scale

Performance of rapid tests for detection of HBsAg and anti-HBsAb in a large cohort, France

Background & Aims: The systematic use of rapid tests performed at points-of-care may facilitate hepatitis B virus (HBV) screening and substantially increase HBV infection awareness. The aim of this study was to evaluate the effectiveness of such tests for HBsAg and anti-HBsAb detection among individuals visiting a variety of healthcare centers located in a low HBV-prevalent area. Methods: Three rapid tests for hepatitis B surface antigen (HBsAg) detection (VIKIA Ò , Determine™ and Quick Profile™) and one test for anti-hepatitis B surface antibody (anti-HBsAb) detection (Quick Profile™) were evaluated in comparison to ELISA serology. Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and area under the ROC curve were used to estimate test performance. Non-inferiority criteria of the joint Se, Sp were set at 0.80, 0.95. Results: Among the 3956 subjects screened, 85 (2.1%) were HBsAg-positive and 2225 (56.5%) had a protective anti-HBsAb titer. Test Se and Sp (lower bound of 97.5% CI) were as follows: 96.5% (89.0%), 99.9% (99.8%) for Vikia Ò ; 93.6% (80.7%), 100.0% (99.8%) for Determine™; and 90.5% (80.8%), 99.7% (99.5%) for Quick Profile™; with all three tests achieving minimal noninferiority criteria. False negatives were typically observed in inactive HBsAg carriers. The anti-HBsAb Quick Profile™ test had excellent specificity (97.8%) and PPV (97.8%) albeit low sensitivity (58.3%), thus failing to establish non-inferiority. Conclusions: All three HBsAg rapid tests could be considered ideal for HBV screening in low HBV-prevalent countries, given the ease of use, rapidity, and high classification probabilities. The anti-HBsAb Quick Profile™ could be considered reliable only for positive tests.

Current State of and Needs for Hepatitis B Screening: Results of a Large Screening Study in a Low-Prevalent, Metropolitan Region

<div><p>Background</p><p>In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing.</p><p>Methods</p><p>During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals.</p><p>Results</p><p>85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8–100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0–93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3–47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6–32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU.</p><p>Conclusions</p><p>Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.</p></div

Comparison of testing practices with respect to HBV-infection status.

<p>*Comparing HBV-status in column with non-immunized/vaccinated individuals.</p>1<p>If the study physician would have tested the participant for HBV per study center's protocol.</p>2<p>If a participant would have been tested using the Center for Disease Control and Prevention (CDC) criteria for HBV screening.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092266#pone.0092266-Weinbaum1" target="_blank">[7]</a>.</p

Definition of HBV infection status.

<p>Definition of HBV infection status.</p

Determinants of testing practices and HBsAg-positive status.

<p>For each endpoint, all variables in the risk-factor column were used in the multivariable logistic regression model except for those with “—”. Further details on model construction are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092266#pone.0092266.s001" target="_blank">Table S1</a>.</p><p>*Thirteen patients were excluded from analysis as they had missing data on parent's geographical origin.</p><p>**Fifteen patients were excluded from analysis as 13 had missing data on parent's geographical origin, one had missing age, and one had missing physician's recommendation for testing.</p>1<p>Endpoint defined as if the study physician would have tested the participant for HBV per study center's protocol.</p>2<p>Includes participants with government assistance (CMU, AME) and “other” health insurance plans.</p

Performance of testing practices for HBsAg-positive individuals.

1<p>If the study physician would have tested the participant for HBV per study center's protocol. One non-exposed participant had missing information and was excluded from this analysis.</p>2<p>If a participant would have been tested using the Center for Disease Control and Prevention (CDC) criteria for HBV screening <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092266#pone.0092266-Weinbaum1" target="_blank">[7]</a>.</p

HBV-infection status within groups of risk-factors for HBV transmission.

<p>HBV, hepatitis B virus; Int., intermediate; MSM, men who have sex with men; IDU, intravenous drug use.</p