Increase over time of antibody levels 3 months after a booster dose as an indication of better protection against Omicron infection.

The third, "booster", vaccination increases the overall immune response against SARS-CoV-2 variants. However, after the initial peak at around 3 weeks post-vaccination, anti-spike antibody levels decline. Post-booster kinetics of cellular response has been less investigated and there is no documented evidence of a true boosting effect. Furthermore, multiple studies underline the less effective immune responses against Omicron, the latest variant of concern, at both humoral and cellular levels. In this letter, we analyse humoral (anti-RBD IgG levels) and cellular (IFN-γ release assay) immune response in 205 health care workers 3 weeks and 3 months after administration of an mRNA-based booster dose, either mRNA-1273 or BNT162b2. Since all subjects were SARS-CoV-2 infection-naïve, we also looked at the incidence of Omicron infection between 3 and 6 months post-booster.At both timepoints, 3x mRNA-1273 vaccination had the highest overall antibody and IFN-γ levels, followed by 3x BNT162b2 vaccination and heterologous mRNA-based regimens. Heterologous ChAdOx1-mRNA-based regimen had the lowest antibody levels while cellular response equal to that of 3x BNT162b2 vaccination and heterologous mRNA-based regimens. Our results show that both humoral and cellular responses waned at 3 months for all vaccination regimens. However, we identified three trajectories of dosage variation. Interestingly, the subgroup of subjects with increasing anti-RBD IgG levels over time had a lower incidence of Omicron infection. Whether increasing humoral response at 3 months post-booster is more indicative of protection than a high initial peak remains to be confirmed in a larger cohort.

Monitoring of SARS-CoV-2 Infection in Ragusa Area: Next Generation Sequencing and Serological Analysis.

The coronavirus disease 19 (COVID-19) post pandemic evolution is correlated to the development of new variants. Viral genomic and immune response monitoring are fundamental to the surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since 1 January to 31 July 2022, we monitored the SARS-CoV-2 variants trend in Ragusa area sequencing n.600 samples by next generation sequencing (NGS) technology: n.300 were healthcare workers (HCWs) of ASP Ragusa. The evaluation of anti-Nucleocapside (N), receptor-binding domain (RBD), the two subunit of S protein (S1 and S2) IgG levels in 300 exposed vs. 300 unexposed HCWs to SARS-CoV-2 was performed. Differences in immune response and clinical symptoms related to the different variants were investigated. The SARS-CoV-2 variants trend in Ragusa area and in Sicily region were comparable. BA.1 and BA.2 were the most representative variants, whereas the diffusion of BA.3 and BA.4 affected some places of the region. Although no correlation was found between variants and clinical manifestations, anti-N and anti-S2 levels were positively correlated with an increase in the symptoms number. SARS-CoV-2 infection induced a statistically significant enhancement in antibody titers compared to that produced by SARS-CoV-2 vaccine administration. In post-pandemic period, the evaluation of anti-N IgG could be used as an early marker to identify asymptomatic subjects.

Immune Response to CoronaVac and Its Safety in Patients with Type 2 Diabetes Compared with Healthcare Workers.

BACKGROUND: Vaccines for SARS-CoV-2 have been critical for preventing disease. Previous research showed patients with diabetes have impaired immunity. This study aimed to determine the immunity to coronavirus after CoronaVac by comparing patients with type 2 diabetes (T2D) and healthcare workers (HCW). MATERIALS AND METHODS: A prospective cohort study evaluated immune responses and safety after two doses of CoronaVac in T2D and HCW groups at Chulabhorn Hospital. The levels of total antibodies against the receptor-binding domain (anti-RBD) of the SARS-CoV-2 spike protein at baseline and 4 weeks after vaccination were collected. The level of anti-RBD concentrations was reported as geometric mean concentration (GMC) and compared between groups using the geometric mean ratio (GMR). RESULTS: 81 participants were included; 27 had T2D and 54 were HCW. After complete vaccination, anti-RBD concentrations were not significantly different between T2D (57.68 binding antibody units (BAU)/mL, 95% confidence interval (CI) = 29.08; 114.44) and HCW (72.49 BAU/mL, 95% CI = 55.77; 94.22) groups. Subgroup analysis showed the GMC of anti-RBD was significantly lower in T2D patients with dyslipidaemia (50.04 BAU/mL) than in T2D patients without dyslipidaemia (341.64 BAU/mL). CONCLUSIONS: The immune response at 4 weeks after two doses of CoronaVac did not significantly differ between patients with T2D and HCW.

Humoral and cellular response after BNT162b2 vaccine booster in hemodialysis patients and kidney transplant recipients.

BACKGROUND: Vulnerable populations, such as hemodialysis (HD) patients and kidney transplant (RTx) recipients, have priority for anti-COVID-19 vaccination, because of their impaired immune status. Here, we investigated the immune response after vaccination with BNT162b2 (two doses plus booster) in HD and RTx patients. METHODS: A prospective, observational study was started in two homogeneous groups of 55 HD and 51 RTx patients previously matched from a cohort of 336 patients. Anti-RBD IgG levels, assayed after the second dose with BNT162b2 mRNA, were used to stratify subjects into quintiles. After the second dose and after booster, anti-RBD and IGRA test were evaluated in RTx and HD, belonging to the first and fifth quintiles. RESULTS: After the second dose of vaccine, the median circulating levels of anti-RBD IgG were significantly higher in HD (1456 AU/mL) compared to RTx (27.30 AU/mL). IGRA test showed significantly higher values in the HD (382 mIU/mL) compared with the RTx (73 mIU/mL). After the booster, humoral response increased significantly in both HD (p = 0.0002) and RTx groups (p = 0.009), whereas the T-cellular immunity remained essentially stable in most patients. In RTx patients with a low humoral response after the second dose, the third dose did not significantly strengthen either humoral or cellular immunity. CONCLUSIONS: For HD and RTx, there is great variability in the humoral response to anti-COVID-19 vaccination, with a stronger response in the HD group. The booster dose was ineffective at reinforcing the humoral and cellular immune response in most RTx patients hyporesponsive to the second dose.

Third dose of SARS-CoV2 mRNA vaccination produces robust persistent cellular and humoral immune responses in liver transplant recipients.

Weaker responses have been described after two doses of anti-SARS-CoV2 vaccination in liver transplant recipients (LTRs). At the Italian National Institute for Infectious Diseases, 122 LTRs (84% males, median age 64 years) were tested for humoral and cell-mediated immune response after a third doses of anti-SARS-CoV2 mRNA vaccines. Humoral response was measured by quantifying anti-receptor binding domain and neutralizing antibodies; cell-mediated response was measured by quantifying IFN-γ after stimulation of T cells with SARS-CoV-2-specific peptides. Humoral and cellular responses improved significantly compared to the second vaccine dose; 86.4% of previous non-responders to the first 2 vaccine doses (N = 22) became responders. Mycophenolate mofetil-containing regimens were not associated with lower response rates to a third vaccine; shorter time since transplantation (<6 years) was associated with lower humoral and cellular responses to third vaccine. Protective antibodies against Omicron variant were detected in 60% of patients 12 weeks after third vaccine dose.

Omicron B.1.1.529 variant infections associated with severe disease are uncommon in a COVID-19 under-vaccinated, high SARS-CoV-2 seroprevalence population in Malawi.

Background: The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions. Methods: We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalisations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. A multivariable logistic regression model was developed to investigate the factors associated with SARS-CoV-2 seropositivity. Findings: Serum samples were analysed from 4619 participants (57% female; 60% aged 18-50 years), of whom 878/3794 (23%) of vaccine eligible adults had received a single dose of any COVID-19 vaccine. The overall assay-adjusted seroprevalence was 83.7% (95% confidence interval (CI), 79.3%-93.4%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18-50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (1 dose, 94% vs. 77%, adjusted odds ratio 4.89 [95% CI, 3.43-7.22]; 2 doses, 97% vs. 77%, aOR 6.62 [95% CI, 4.14-11.3]). Urban residents were more likely to be seropositive than those from rural settings (91% vs. 78%, aOR 2.76 [95% CI, 2.16-3.55]). There was at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalisations, 10.7% (95% CI, 10.2-11.3) vs. 4.86% (95% CI, 4.52-5.23), p < 0.0001; deaths, 3.48% (95% CI, 3.18-3.81) vs. 1.15% (95% CI, 1.00-1.34), p < 0.0001). Interpretation: We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence and low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of reported at-risk populations. Funding: Supported by the Bill and Melinda Gates Foundation (INV-039481).

Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution.

BACKGROUND: We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group). METHODS: This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1-negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined. RESULTS: At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4-654.9) and 171.9 (61.8-425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145-824) and 555.8 (166.4-1751) BAU/mL in the HIV>500 group and 274.7 (193.7-680.4) and 281.6 (181-831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01). CONCLUSIONS: One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.

Evaluation of the analytical performance of three chemiluminescence serological assays for detecting anti-SARS-CoV-2 antibodies.

The serology surveillance of SARS-CoV-2 antibodies represents a useful tool for monitoring protective immunity in the population. We compared the performance of three SARS-CoV-2 antibody serological immunoassays in 600 vaccinated subjects after the BNT162b2 mRNA COVID-19 vaccine. All serum samples were evaluated by three different immunoassays for detecting anti-SARS-COV-2 antibodies. All SARS-CoV-2 antibody serological immunoassays could detect, when present, a post-vaccine humoral immune response. Median (interquartile range, IQR) anti-S-RBD IgG, Access SARS-CoV-2 IgG (1st IS) and Access SARS-CoV-2 IgG II levels of the subjects investigated were, respectively, 687 BAU/mL (131-2325), 419 IU/mL (58-1091) and 104 AU/mL (14-274). By studying a cohort of unvaccinated subjects, without previous COVID-19 infection, we found a high specificity for all methods. A high correlation was found between IgG titres. Considering the kinetics of subjects with multiple doses, we observed that percentage decreasing gradients were comparable across methods. Our results suggest that all the SARS-CoV-2 antibody serological immunoassays evaluated in this study are suitable for monitoring IgG titers over time. This study contributes to a better understanding of antibody response in vaccinated subjects using some currently available assays.

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan.

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

Optical Biosensor for the Detection of Infectious Diseases Using the Copolymer F8T2 with Application to COVID-19.

The coronavirus pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the development of biosensors based on new materials and techniques. Here, we present our effort to develop a fast and affordable optical biosensor using photoluminescence spectroscopy for anti-SARS-CoV-2 antibody detection. The biosensor was fabricated with a thin layer of the semiconductor polymer Poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-2,2'-bithiophene-5,5'-diyl)] (F8T2) as a signal transducer material. We mounted the biosensors by depositing a layer of F8T2 and an engineered version of RBD from the SARS-CoV-2 spike protein with a tag to promote hydrophobic interaction between the protein and the polymeric surface. We validated the biosensor sensitivity with decreasing anti-RBD polyclonal IgG concentrations and challenged the biosensor specificity with human serum samples from both COVID-19 negative and positive individuals. The antibody binding to the immobilized antigen shifted the F8T2 photoluminescence spectrum even at the low concentration of 0.0125 µg/mL. A volume as small as one drop of serum (100 µL) was sufficient to distinguish a positive from a negative sample without requiring multiple washing steps and secondary antibody reactions.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response After Heterologous Immunizations With ChAdOx1/BNT162b2 in End-Stage Renal Disease Patients on Hemodialysis.

The Korean government decided to schedule heterologous vaccinations on dialysis patients for early achievement of immunization against Coronavirus disease 2019(COVID-19). However, the effects of heterologous immunizations in hemodialysis (HD) patients are unclear. One hundred (HD) patients from Gangdong Kyung Hee University Hospital and Kyung Hee Medical Center and 100 hospital workers from Gangdong Kyung Hee University Hospital were enrolled in this study. The HD patients received the mixing schedule of ChAdOx1/BNT162b2 vaccinations at 10-week intervals, while hospital workers received two doses of ChAdOx1 vaccines at 12-week intervals. Serum IgG to a receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 was measured 1 month after the first dose, 2 months and 4 months after the second dose. The median [interquartile range] anti-RBD IgG was 82.1[34.5, 176.6] AU/ml in HD patients and 197.1[124.0, 346.0] AU/ml in hospital workers (P < 0.001) after the first dose. The percentage of positive responses (IgG > 50 AU/ml) was 65.0% and 96.0% among the both group, respectively (P < 0.001). The anti-RBD IgG levels increased significantly by 2528.8 [1327.6, 5795.1] AU/ml with a 100.0% positive response rate in HD patients 2 months after the second dose, which was higher than those in hospital workers 981.4[581.5, 1891.4] AU/ml (P < 0.001). Moreover, anti-RBD IgG remains constantly high, and positive response remains 100% in HD patients 4 months after the second dose. This study suggests that heterologous vaccinations with ChAdOx1/BNT162b2 can be an alternative solution on HD patients for early and strong induction of humoral response.

Humoral Immune Response Diversity to Different COVID-19 Vaccines: Implications for the "Green Pass" Policy.

In the COVID-19 pandemic year 2021, several countries have implemented a vaccine certificate policy, the "Green Pass Policy" (GPP), to reduce virus spread and to allow safe relaxation of COVID-19 restrictions and reopening of social and economic activities. The rationale for the GPP is based on the assumption that vaccinated people should maintain a certain degree of immunity to SARS-CoV-2. Here we describe and compare, for the first time, the humoral immune response to mRNA-1273, BNT162b2, Ad26.COV2.S, and ChAdOx1 nCoV-19 vaccines in terms of antibody titer elicited, neutralizing activity, and epitope reactogenicity among 369 individuals aged 19 to 94 years. In parallel, we also considered the use of a rapid test for the determination of neutralizing antibodies as a tool to guide policymakers in defining booster vaccination strategies and eligibility for Green Pass. Our analysis demonstrates that the titer of antibodies directed towards the receptor-binding domain (RBD) of SARS-CoV-2 Spike is significantly associated with age and vaccine type. Moreover, natural COVID-19 infection combined with vaccination results, on average, in higher antibody titer and higher neutralizing activity as compared to fully vaccinated individuals without prior COVID-19. We also found that levels of anti-Spike RBD antibodies are not always strictly associated with the extent of inhibition of RBD-ACE2 binding, as we could observe different neutralizing activities in sera with similar anti-RBD concentrations. Finally, we evaluated the reactivity to four synthetic peptides derived from Spike protein on a randomly selected serum sample and observed that similar to SARS-CoV-2 infection, vaccination elicits a heterogeneous antibody response with qualitative individual features. On the basis of our results, the use of rapid devices to detect the presence of neutralizing antibodies, even on a large scale and repeatedly over time, appears helpful in determining the duration of the humoral protection elicited by vaccination. These aspects and their implications for the GPP are discussed.

Sequential Profiling of Anti-SARS CoV-2 IgG Antibody in Post COVID-19 Patients.

Upon SARS CoV-2 infection, humoral immune system triggers production of anti-SARS CoV-2 IgM and IgG antibodies. Currently, antibodies against SARS CoV-2 spike protein receptor binding domain play a central role in disease protection, making them potential target for in vitro diagnostics applications. This study determines the expression level and sustainability of anti-receptor binding domain (RBD) SARS CoV-2 IgG in post COVID-19 patients. Anti-RBD SARS CoV-2 IgG antibodies in patient serum were analysed by standardised indirect ELISA using SARS CoV-2 spike receptor binding domain protein and HRP conjugated anti-human IgG antibody (anti-h IgG). The study was conducted using 35 adult patient samples with confirmed SARS CoV-2 infection. Additionally, correlation between antibody response after each stage and disease symptoms in post COVID-19 patients were studied. Maximum antibody titre was seen at Day 40 and decreased relatively to Day 180 in antibody positive samples when compared with controls. Overall, more IgG antibody expression is observed in patients who suffered from loss of smell and taste at Day 40. 71% of the positive subjects in this study showed high SARS CoV-2 IgG antibody concentration of above 10 ng/mL and 37% showed strong antibody concentration above 20 ng/mL at the peak of seroconversion.

Differential Dynamics of Humoral and Cell-Mediated Immunity with Three Doses of BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers in Japan: A Prospective Cohort Study.

Vaccines against SARS-CoV-2 with good efficacy are now available worldwide. However, gained immunity diminishes over time. Here, we investigate the course of both humoral and cell-mediated immunity in response to three doses of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine in healthcare workers in Japan. SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies (total Ig, IgG), neutralizing antibodies (NAb), and ELISpot were measured in serum and whole blood samples collected after each vaccine dose. ELISpot numbers were higher than the cutoff values in most participants at all times. It was suggested that the difference in behavior between humoral immunity and cell-mediated immunity with age is complementary. Anti-RBD total Ig, IgG, and NAb indicated a high correlation at each time point after vaccine doses. Total Ig was retained long-term after the second dose and increased significantly faster by the booster dose than IgG. Nab levels of all subjects were ≤20% six months after the second dose, and the correlation coefficient was greatly reduced. These are due to the avidity of each antibody and differences among commercial kits, which may affect the evaluation of immunokinetics in previous COVID-19 studies. Therefore, it is necessary to harmonize reagents categorized by the same characteristics.

Longitudinal dynamics of SARS-CoV-2 anti-receptor binding domain IgG antibodies in a wide population of health care workers after BNT162b2 vaccination.

OBJECTIVES: With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies evolved toward quantitative assays directed to the spike glycoprotein or its receptor-binding domain (RBD). The objective was to perform a large-scale, longitudinal study involving health care workers (HCWs), with the aim of establishing the kinetics of immune response throughout the 9-month period after receipt of the second dose of the BNT162b2 vaccine. METHODS: Quantitative determination of immunoglobulin (Ig) G antibodies against the RBD of the S1 subunit of the spike protein of SARS-CoV-2 on the Alinity systems. RESULTS: The highest levels of anti-RBD IgG were measured after 1 month from full vaccination (median: 1432 binding antibody units/ml [BAU/ml]); subsequently, a steep decrease (7.4-fold decrease) in IgG levels was observed at 6 months (median: 194.3 BAU/ml), with a further 2.5-fold decrease at 9 months (median: 79.3 BAU/ml). Furthermore, the same data, when analyzed for sex, showed significant differences between male and female participants at both 1 and 9 months from vaccination, but not at 6 months. CONCLUSION: Our results confirm the tendency of anti-RBD antibodies to decrease over time, also when extending the analysis up to 9 months, and highlight a better ability of the female sex to produce antibodies 1 month and 9 months after vaccination. Overall, these data, obtained in a wide population of HCWs, support the importance of having increased the vaccine doses.

Evaluation of commercial Anti-SARS-CoV-2 neutralizing antibody assays in seropositive subjects.

The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.

Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity and in Healthy Controls: A Single Center Study.

Background: Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited. Methods: A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety. Results: Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-α producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine. Conclusion: All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.

Dynamics of seroprevalence of anti-SARS-CoV-2 antibodies in non-vaccinated people

Objective. To assess the dynamics of seroprevalence of anti-SARS-CoV-2 antibodies in the population of non-vaccinated people. Materials and methods. During two months of the last quarter of 2020 (before the start of mass vaccination against the coronavirus infection), we analyzed the dynamics of the level of total anti-SARS-CoV-2 IgG and level of virus-neutralizing IgG (anti-RBD/S1) in 806 unvaccinated people without clinical signs of the disease Results. Upon first examination, 16.0% of participants were found to have positive total anti-SARS-CoV-2 IgG, while 82.6% were negative and 1.4% had indeterminate result. During two months of the pandemic, seroprevalence increased by 23.7% (from 16.0% to 39.7%). The proportion of people with an indeterminate result remained the same (1.4%). The proportion of patients with asymptomatic COVID-19 who were initially IgG-positive but became negative in two months was 5.4%. Some individuals with positive total anti-SARS-CoV-2 IgG were found to have non-reactive anti-RBD antibodies that did not ensure neutralization of coronavirus (17.8% upon first and 10.6% upon second examination). © 2021, Dynasty Publishing House. All rights reserved.

Humoral immune response after COVID-19 infection or BNT162b2 vaccine among older adults: evolution over time and protective thresholds.

The objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD-IgG response over time among older people after COVID-19 infection or vaccination and its comparison with indicative levels of protection. Geriatric patients with SARS-CoV-2 serological test results were included and divided into three groups. A vaccine group (n = 34), a group of natural COVID-19 infection (n = 32), and a group who contracted COVID-19 less than 15 days after the first injection (n = 17). Eighty-three patients were included; the median age with IQR was 87 (81-91) years. In the vaccine group at 1 month since the first vaccination, the median titer of anti-RBD-IgG was 620 (217-1874) BAU/ml with 87% of patients above the theoretical protective threshold of 141 BAU/ml according to Dimeglio et al. (J Infec. 84(2):248-88, [7]). Seven months after the first vaccination, this titer decreased to 30 (19-58) BAU/ml with 9.5% of patients > 141 BAU/ml. In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median titer was 798 (325-1320) BAU/ml with 86.7% of patients > 141 BAU/ml and fell to 88 (37-385) with 42.9% of patients > 141 BAU/ml at 2 months. The natural infection group was vaccinated 3 months after the infection. Five months after the vaccination cycle, the median titer was 2048 (471-4386) BAU/ml with 83.3% of patients > 141 BAU/ml. This supports the clinical results describing the decrease in vaccine protection over time and suggests that vaccination after infection can maintain significantly higher antibody titer levels for a prolonged period of time.