Evaluation of Rapid Lateral-Flow Tests Directed against the SARS-CoV-2 Nucleoprotein Using Viral Suspensions Belonging to Different Lineages of SARS-CoV-2.

Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era.

Management of COVID-19 on board the mixed cargo ship Aranui 5.

BACKGROUND: During cruises, the management of coronavirus disease 2019 (COVID-19) infections poses serious organizational problems such as those encountered in 2020 by the Zaandam, the aircraft carrier Charles de Gaulle or the Diamond Princess. In French Polynesia, the mixed cargo ship Aranui 5 transports both tourists and freight to the Marquesas Islands. The purpose of this article is to show how COVID-19 infections were diagnosed and contained before and after passengers boarded a cruise. MATERIALS AND METHODS: On October 15, 2020, 161 passengers including 80 crew members embarked for a 13-day voyage from Papeete to the Marquesas Islands. Prior to boarding, all passengers underwent a reverse transcriptase-polymerase chain reaction (RT-PCR) test; the tests results were all negative. On Day 0, 3, 5, 8 and 11, Biosynex® rapid antigen diagnostic tests were carried out on all or some of the crew members and tourists who may have had contact with new positive cases. Each day, forehead or temporal temperatures were measured using an infrared thermometer and questions were asked concerning the subjects' health status. When a subject was positive, the person and their contacts were isolated in individual cabins. The infected person then left the vessel to be received in a communal reception centre on the nearest island. RESULTS: A total of 9 positive cases were observed, including two before departure (a tourist and a crew member). During the trip, 7 crew members tested positive. The patients and their contacts were isolated and then disembarked at the earliest opportunity. At the time of sampling, the subjects were asymptomatic. The patients and their contacts all became symptomatic within 24 to 48 hours after sampling. CONCLUSIONS: In total, the voyage could be completed without any transmission on board among the tourists and with a minimum transmission among the crew members, thus maintaining the tourist and economic activity of the islands during the times of COVID-19 pandemic.

A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

Performance of the COVID19SEROSpeed IgM/IgG Rapid Test, an Immunochromatographic Assay for the Diagnosis of SARS-CoV-2 Infection: a Multicenter European Study.

This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen's kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.

Tick-Borne Encephalitis in Auvergne-Rhône-Alpes Region, France, 2017-2018.

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.

The variable sensitivity of HIV Ag/Ab combination assays in the detection of p24Ag according to genotype could compromise the diagnosis of early HIV infection.

BACKGROUND: In France, HIV infection diagnosis was modified by a decree, published in 2010, that requires the use of HIV Ag/Ab assays able to detect at least 2 IU/ml of p24Ag. This measure raises the concern of the capacity of these assays to equally detect all HIV variants. OBJECTIVES: To assess the performance of HIV Ag/Ab assays for the detection of p24Ag from diverse HIV isolates. STUDY DESIGN: Ten HIV Ag/Ab assays were compared using two p24Ag reference standards, 297 samples from 99 HIV-1 and HIV-2 cell-culture derived isolates including various subtypes and groups, and 9 native specimens from subjects with primary HIV infection. RESULTS: The p24Ag limit of detection (LOD) ranged from 0.505 IU/ml to 1.90 1 IU/ml and, from 11.9 pg/ml to 33.5 pg/ml when using WHO and French national standards, respectively. The overall percentage of positive samples ranged from 26.8% to 74.5%. Five assays failed to detect all dilutions of at least one group M subtype, three missed all group O and six all the group P samples. Three assays were able to detect 2-10 of the 30 HIV-2 samples. The distribution of LODs for each group M isolate showed a wide dispersion between the assays. Percentage of isolates detected at a p24Ag level less than 2 IU/ml varied from 22% to 98.7%. CONCLUSION: This study demonstrated that, even though their analytical sensitivity fulfills the requirements, many of HIV Ag/Ab assays could fail to detect HIV primary infection due to HIV-1 non-B, non-M and HIV-2 strains.

Clinical performance of the carbohydrate-deficient transferrin (CDT) assay by the Sebia Capillarys2 system in case of cirrhosis. Interest of the Bio-Rad %CDT by HPLC test and Siemens N-Latex CDT kit as putative confirmatory methods.

BACKGROUND: The CDT assay used to detect chronic alcohol abuse is difficult with cirrhotic patients. This article describes the performances of several CDT assays in case of cirrhosis. The CDT-Capillarys assay by capillary zone electrophoresis was used for initial testing. Two additional methods were tested as putative confirmatory methods. METHODS: 110 patients with known hepatic status had their CDT measured by the Capillarys2 or alternative methods. Self-reported alcohol intake was used to assess the performances of CDT assays. RESULTS: Capillarys2 performance was lower in case of cirrhosis, many electropherograms displaying various abnormalities. We used the proper separation of the di- and tri-sialotransferrin peaks to select reliable profiles. This selection led to the classification of cirrhotic and non-cirrhotic patients in abusers and abstainers with similar performances. However, no interpretation was available for 54% of the cirrhotic patients and neither the BioRad %CDT by HPLC test, nor the Siemens N-Latex CDT kit was suitable as confirmatory methods for these samples. CONCLUSIONS: An attentive profile examination is required for the validation of Capillarys CDT results of cirrhotic patients. Reliability is significantly improved when samples with an improper separation are excluded. To date, no commercial test can confirm the excluded samples.

Sensitivities of four new commercial hepatitis B virus surface antigen (HBsAg) assays in detection of HBsAg mutant forms.

Mutations in hepatitis B virus surface antigen (HBsAg) involving amino acid substitution within the immunodominant "a" determinant may affect the performance of commercial HBsAg assays. The performances of four HBsAg assays that recently received Conformité Européene marking, Advia Centaur HBsAg (Bayer), Monolisa HBsAg Ultra (Bio-Rad), Liaison HBsAg (Dia Sorin), and Vidas HBsAg Ultra (bioMérieux), were compared with that of the routinely used HBsAg assay AxSYM HBsAg V2 (Abbott). Assays were evaluated for (i) analytical sensitivity performance with a national reference HBsAg panel (including 10 samples with calibrated HBsAg concentrations from 0.04 to 2.24 ng/ml) and (ii) the detection of HBsAg mutants by studying a panel of 35 HBsAg mutants (23 collected from patients and 12 recombinant mutants). The limits of detection of these assays were <0.15 ng/ml (from 0.089 to 0.121 ng/ml). The sensitivity performances for mutant virus detection varied, ranging from 37.1% to 91.4%. The lack of detection of these mutants by commercial assays was probably due to the epitope recognition of the anti-HBs assay reagents in the capture phase and in the conjugates. The prevalence and clinical impact of HBsAg mutants are under investigation. However, the manufacturers must be vigilant in the design of the assays in order to reduce the risk of missing a broad range of described S gene mutants.