Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

An omicron-based vaccine booster elicits potent neutralizing antibodies against emerging SARS-CoV-2 variants in adults.

SARS-CoV-2 Omicron subvariants have become the predominantly strain in most countries. However, the neutralizing activity of the human serum after Omicron-based vaccine booster against different SARS-CoV-2 variants is poorly understood. Here, we developed an update Omicron vaccine (SCoK-Omicron), based on the RBD-Fc fusion protein vaccine (SCoK) and RBD domain of Omicron BA.1. To assess cross-variant neutralizing activity in adults, 25 volunteers that have received three doses of SCoK and 25 volunteers with two doses of CoronaVac (inactive vaccine) were further boosted with a dose updated vaccine (SCoK-Omicron). The results of pseudovirus neutralization assays demonstrated that the booster potently induced the high-level of neutralizing antibody against SARS-CoV-2 Wild type, Delta and Omicron subvariants in adults. Further assays of single point mutations showed that K444T, L452R, N460K, or F486V was key mutations to cause immune evasion. Together, these data suggest that SCOK-Omicron can be used as a booster vaccine candidate in adults receiving subunit protein or inactivated vaccine in response to the epidemic of COVID-19 Omicron subvariants, and the mutation K444T, L452R, N460K, or F486V needs to be considered in future vaccine design.

Association between reactogenicity and immunogenicity after BNT162b2 booster vaccination: a secondary analysis of a prospective cohort study.

OBJECTIVES: A weak correlation between symptom severity and antibody levels after primary immunization against COVID-19 has already been shown. This study aimed to describe the association between reactogenicity and immunogenicity after booster vaccination. METHODS: This secondary analysis of a prospective cohort study included 484 healthcare workers who received a booster vaccination with BNT162b2. Anti-receptor binding domain (RBD) antibodies were assessed at baseline and 28 days after booster vaccination. Side effects were graded (none, mild, moderate, or severe) and reported daily for 7 days after booster vaccination. Spearman correlation coefficient (rho) was used to determine the correlations between the severity of each symptom and anti-RBD levels before vaccination and 28 days after. The Bonferroni method was used to adjust p values for multiple comparisons. RESULTS: Most of the 484 participants reported at least one local (451 [93.2%]) or systemic (437 [90.3%]) post-booster symptom. No correlations between the severity of local symptoms and antibody levels were found. Except for nausea, systemic symptoms showed weak but statistically significant correlations with 28-day anti-RBD levels (fatigue [rho = 0.23, p < 0.01], fever [rho = 22, p < 0.01], headache [rho = 0.15, p 0.03], arthralgia [rho = 0.2, p < 0.01], myalgia [rho = 0.17, p < 0.01]). There was no association between post-booster symptoms and pre-booster antibody levels. DISCUSSION: This study showed only a weak correlation between the severity of systemic post-booster symptoms and anti-SARS-CoV-2 antibody levels at 28 days. Therefore, self-reported symptom severity cannot be used to predict immunogenicity after booster vaccination.

A Longitudinal Study in Turkiye of Host Ability to Produce Antibodies following a Third Homologous BNT162b2 Vaccination.

Obesity is a multifaceted, complex condition that has negative impacts on one's health. There are conflicting reports regarding the COVID-19 vaccine's ability to induce antibody formation in obese people. Our study aimed to determine anti-S-RBD IgG and surrogate neutralizing antibody (snAb) levels before and after the third Pfizer-BioNTech (BNT162b2) vaccination (at 15, 60, 90, and 120 days) in normal-weight adults, overweight, and obese individuals without any comorbidity or previous SARS-CoV-2 infection history, but it did not evaluate the response to the first two doses. In this longitudinal prospective study in Istanbul, Turkey, a total of 323 consecutive adult individuals (141 normal weight, 108 overweight, and 74 patients with obesity) were included. Peripheral blood samples were collected. Anti-S-RBD IgG and surrogate neutralizing antibody levels were detected using the ELISA method. After the third dose of BNT162b2 vaccination, obese patients had significantly lower levels of snAb against SARS-CoV-2 compared with normal-weight controls, but the levels otherwise did not differ between the study groups. Across all individuals in our cohort, titers peaked about a month after this third vaccination and then gradually faded. Anti-S-RBD IgG and snAb IH% levels against SARS-CoV-2 were not correlated with IL-6 and TNF-α levels. In conclusion, anti-S-RBD IgG titers and snAb IH% levels against SARS-CoV-2 were determined longitudinally for 120 days after the third homologous BNT162b2 vaccination. Although there were no significant differences in anti-S-RBD IgG, we found significant differences in the snAb IH% levels against SARS-CoV-2 between obese and healthy control subjects.

Comparison of Igm/Igg Antibody Tests in Severe COVID Infections and Standard rtPCR Diagnostic Testing in The Hospital for Active Treatment "Dr. Atanas Dafovski”, Kardzhali

We present the results from ELISA IgG/IgM tests vs rtPCR diagnostic testing of individuals both with and without clinical symptoms, travel arrangements and cross-border movement, in an effort to contain the COVID-19 pandemic during the entire 2021. rtPCR test results were a prerequisite for any planned trip, requirement for diagnosis and protocol treatment. The collected data are cumulative and the statistics might become helpful to each individual in deciding on a particular line of action. Our Molecular Diagnostics Unit is licensed within the territory of Bulgaria. Our methods present strict protocols from the guidelines of the National Center for Infectious and Parasitic Diseases, the kits used were all CE, the overall concept in sync with the global regulations per CDC and the WHO. The cumulated results for each month show high correlation between the levels of IgM and the number of patients testing positive for COVID with the rtPCR. We present retrospective data of utmost importance for the regions near border crossing point in a situation of pandemic with involvement of local and international authorities. Determining the titer of Covid antibodies provides important information with regard to vaccination and compare levels of titers of acute elevated IgM titers in patients with severe COVID-19 with positive PCR results in an attempt to implement more ELISA testing as a significant, informative and important part of establishing a patient's status, given the easier access to rapid tests when triaging patients for admission to hospital and with the need for emergency resuscitation. © 2022, Bulgarian Society for Microbiology (Union of Scientists in Bulgaria). All rights reserved.

Intestinal Viral Loads and Inactivation Kinetics of Livestock Viruses Relevant for Natural Casing Production: a Systematic Review and Meta-Analysis.

Animal intestines are the source of edible sausage casings, which are traded worldwide and may come from areas where notifiable infectious animal diseases are prevalent. To estimate the risks of virus contamination, knowledge about the quantity of virus and decimal reduction values of the standard preservation method by salting is of great importance. A literature search, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed in search engine CAB Abstracts to determine the viral load of 14 relevant animal viruses in natural casings or intestines. Only a very limited number of scientific publications per virus were found and viral loads in the intestines varied from high for ASFV (five publications), BVDV (3), CSFV (6), PPRV (3), RPV(2) and TGEV (3) to moderate for PEDV (2) and SVDV (3), low for HEV (2) and FMDV (5), very low for VESV (1) and negative for PrV (2) and VSV (1). PRRSV was found in intestines, however, viral titers were not published. Three viruses (BVDV, CSFV and PPRV) with high viral loads were selected to search for their inactivation kinetics. For casings, no inactivation data were found, however, thermal inactivation data of these viruses were available, but differed in quantity, quality and matrices. In conclusion, important data gaps still exist when it comes to the quantitative inactivation of viruses in sausage casings or livestock intestines.

Could Prior COVID-19 Affect the Neutralizing Antibody after the Third BNT162b2 Booster Dose: A Longitudinal Study.

Vaccination is an essential public health measure for preventing the spread of illness during this continuing COVID-19 epidemic. The immune response developed by the host or the continuation of the immunological response caused by vaccination is crucial since it might alter the epidemic's prognosis. In our study, we aimed to determine the titers of anti-S-RBD antibody and surrogate neutralizing antibody (snAb) formed before and after the third dose of the BNT162b2 vaccination (on the 15th, 60th, and 90th days) in healthy adults who did not have any comorbidity either with or without prior SARS-CoV-2 infection. In this longitudinal prospective study, 300 healthy persons were randomly included between January and February 2022, following two doses of BNT162b2 immunization and before a third dosage. Blood was drawn from the peripheral veins. SARS-CoV-2 NCP IgG and anti-S-RBD IgG levels were detected by the CMIA method, and a surrogate neutralizing antibody was seen by the ELISA method. Our study included 154 (51.3%) female and 146 (48.7%) male (total 300) participants. The participants' median age was 32.5 (IQR:24-38). It was discovered that 208 individuals (69.3%) had never been infected with SARS-CoV-2, whereas 92 participants (30.7%) had SARS-CoV-2 infections in the past. Anti-S-RBD IgG and nAb IH% levels increased 5.94- and 1.26-fold on day 15, 3.63- and 1.22-fold on day 60, and 2.33- and 1.26-fold on day 90 after the third BNT162b2 vaccine dosage compared to pre-vaccination values (Day 0). In addition, the decrease in anti-S-RBD IgG levels on the 60th and 90th days was significantly different in the group without prior SARS-CoV-2 infection compared to the group with past SARS-CoV-2 infection (p < 0.05). In conclusion, it was observed that prior SARS-CoV-2 infection and the third BNT162b2 vaccine dose led to a lower decrease in both nAb and anti-S-RBD IgG levels. To evaluate the vaccine's effectiveness and update immunization programs, however, it is necessary to perform multicenter, longer-term, and comprehensive investigations on healthy individuals without immune response issues, as there are still circulating variants.

The detectable anti-interferon-γ autoantibodies in COVID-19 patients may be associated with disease severity.

BACKGROUND: Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections. METHODS: To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus disease 2019 (COVID-19), we examined the titers and functional neutralization of anti-IFN-γ autoantibodies in COVID-19 patients. In 127 COVID-19 patients and 22 healthy controls, serum titers of anti-IFN-γ autoantibodies were quantified using enzyme-linked immunosorbent assay, and the presence of autoantibodies was verified with immunoblotting assay. The neutralizing capacity against IFN-γ was evaluated with flow cytometry analysis and immunoblotting, and serum cytokines levels were determined using the MULTIPLEX platform. RESULTS: A higher proportion of severe/critical COVID-19 patients had positivity for anti-IFN-γ autoantibodies (18.0%) compared with non-severe patients (3.4%, p < 0.01) or healthy control (HC) (0.0%, p < 0.05). Severe/critical COVID-19 patients also had higher median titers of anti-IFN-γ autoantibodies (5.01) compared with non-severe patients (1.33) or HC (0.44). The immunoblotting assay could verify the detectable anti-IFN-γ autoantibodies and revealed more effective inhibition of signal transducer and activator of transcription (STAT1) phosphorylation on THP-1 cells treated with serum samples from anti-IFN-γ autoantibodies-positive patients compared with those from HC (2.21 ± 0.33 versus 4.47 ± 1.64, p < 0.05). In flow-cytometry analysis, sera from autoantibodies-positive patients could also significantly more effectively suppress the STAT1 phosphorylation (median,67.28%, interquartile range [IQR] 55.2-78.0%) compared with serum from HC (median,106.7%, IQR 100.0-117.8%, p < 0.05) or autoantibodies-negative patients (median,105.9%, IQR 85.5-116.3%, p < 0.05). Multivariate analysis revealed that the positivity and titers of anti-IFN-γ autoantibodies were significant predictors of severe/critical COVID-19. Compared with non-severe COVID-19 patients, we reveal that a significantly higher proportion of severe/critical COVID-19 patients are positive for anti-IFN-γ autoantibodies with neutralizing capacity. CONCLUSION: Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.

Longitudinal antibody response kinetics following SARS-CoV-2 messenger RNA vaccination in pregnant and nonpregnant persons.

BACKGROUND: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. OBJECTIVE: We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons. STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test. RESULTS: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). CONCLUSION: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines.

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1,667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials. Inter- and intra-assay precision, specificity, linearity, lower limit of quantitation, and assay robustness parameters successfully met the acceptance criteria. Heme and lipid matrix effects showed minimal interference on the assay. Samples were stable for testing in the assay even with 8 freeze/thaws and up to 24 months in -80 °C storage. The assay was also adapted for variants (Delta and Omicron BA.1/BA.5), with similar validation results. The hACE2 assay showed significant correlation with anti-recombinant S immunoglobulin G levels and neutralizing antibody titers. This assay provides a rapid, high-throughput option to evaluate vaccine immunogenicity. Along with other clinical biomarkers, it can provide valuable insights into immune evasion and correlates of protection and enable vaccine development against emerging COVID-19 variants.

Immunoglobulin Class Profiles of ABO Antibodies in Saliva and Serum of Healthy Individuals

Introduction: The coronavirus disease (COVID-19) pandemic gave rise to studies investigating the association of ABO blood group with COVID-19 susceptibility. It is hypothesized that ABO antibodies might play a role in neutralizing SARS-CoV-2. However, ABO antibodies were exclusively analyzed in blood samples. Investigation of ABO antibodies in saliva, an easy-to-obtain surrogate for respiratory secretions, may provide novel insights into mucosal immunity crucial in early defense against respiratory pathogens. Methods: In this study, saliva and serum samples from healthy individuals with known blood groups were investigated using a flow cytometric method for separate anti-A/anti-B IgA, IgM, and IgG class antibody detection. Saliva samples were additionally tested using hemagglutination-based neutral and indirect anti-human globulin test gel cards. This method comparison was complemented by dilution experiments with a high-titer anti-A/anti-B WHO standard. Results: In saliva, IgA was the most abundant ABO antibody class, followed by IgM;IgG was detected only in low levels in all non-AB blood types. In serum, IgM was the predominant ABO antibody class in all non-AB blood types, followed by IgA and IgG, the latter mainly detected in group O individuals. Saliva and serum samples of group O individuals yielded the highest variability of ABO-specific antibody levels. Regardless of sample material and blood type, major interindividual differences in ABO antibody reactivities were recorded. Antibody levels correlated moderately between these two body fluids. There were no significant sex and age-group differences in ABO antibody levels in both serum and saliva. WHO standard dilution experiments yielded technique-specific limits of detection, illustrating the inherent differences of immunofluorescence versus agglutination. Conclusion: For the first time, salivary ABO antibodies were investigated by separate detection of the three most relevant antibody classes IgA, IgM, and IgG in a healthy cohort. This study opens new perspectives regarding mucosal ABO antibody class profiles and their potential influence on respiratory infections.

Safety and immunogenicity of mRNA COVID-19 vaccine in inpatients with muscular dystrophy.

INTRODUCTION/AIMS: Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease-2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD. METHODS: We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28 to 30 days after the second dose, and antibody titers were measured. RESULTS: Overall, 104 (60.8%) and 115 (67.6%) patients had side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.12 to 0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI, 159.3 to 358.7). Older age (relative risk [RR] = 0.97; 95% CI, 0.95 to 0.99) and bedridden state (RR = 0.27; 95% CI, 0.14 to 0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR = 0.42; 95% CI, 0.21 to 0.85). DISCUSSION: COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs.

Anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 or Post-Vaccination in Libyan Population: Comparison of Four Vaccines.

Measurement of strength and durability of SARS-COV-2 antibody response is important to understand the waning dynamics of immune response to both vaccines and infection. The study aimed to evaluate the level of IgG antibodies against SARS-CoV-2 and their persistence in recovered, naïve, and vaccinated individuals. We investigated anti-spike RBD IgG antibody responses in 10,000 individuals, both following infection with SARS-CoV-2 and immunization with SARS-COV-2 AstraZeneca, Sputnik V, Sinopharm, and Sinovac. The mean levels of anti-spike IgG antibodies were higher in vaccinated participants with prior COVID-19 than in individuals without prior COVID-19. Overall, antibody titers in recovered vaccinee and naïve vaccinee persisted beyond 20 weeks. Vaccination with adenoviral-vector vaccines (AstraZeneca and Sputnik V) generates higher antibody titers than with killed virus vaccine (Sinopharm and Sinovac). Approximately two-thirds of asymptomatic unvaccinated individuals had developed virus-specific antibodies. A single dose of vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with apparent prior SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals. In addition, the high number of seropositivity among asymptomatic unvaccinated individuals showed that the number of infections are probably highly underestimated. Those vaccinated with inactivated vaccine may require more frequent boosters than those vaccinated with adenoviral vaccine. These findings are important for formulating public health vaccination strategies during COVID-19 pandemic.

Humoral Response to SARS-CoV-2 Antigen in Patients Treated with Monoclonal Anti-CD20 Antibodies: It Is Not All about B Cell Recovery.

Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included patients receiving anti-CD20 therapy after antigen contact who were divided into responders (>7 binding antibody units (BAU)/mL) and non-responders (<7 BAU/mL). In participants with first antigen contact prior to therapy, we investigated the recall response elicited once under treatment. We included 80 patients (responders n = 34, non-responders n = 37, recall cohort n = 9). The B-cell counts among responders were significantly higher compared to non-responders (mean 1012 cells/µL ± SD 105 vs. mean 17 cells/µL ± SD 47; p < 0.001). Despite very low B-cell counts (mean 9 cells/µL ± SD 20), humoral response was preserved among the recall cohort (mean 1653 BAU/mL ± SD 2250.1) and did not differ significantly from responders (mean 735 BAU/mL ± SD 1529.9; p = 0.14). Our data suggest that peripheral B cells are required to generate antibodies to neo-antigens but not for a recall response during anti-CD20 therapy. Evaluation of B-cell counts and pre-existing SARS-CoV-2 antibodies might serve as biomarkers for estimating the immune competence to mount a humoral response to SARS-CoV-2 antigens.

Efficacy and safety profile of COVID-19 mRNA vaccine in patients with hematological malignancies: Systematic review and meta-analysis.

Patient populations, including those with hematological malignancies, have different responses to COVID-19 vaccines. This study aimed to quantitatively analyze the efficacy and safety of COVID-19 mRNA vaccines in patients with hematological malignancies. Studies reporting on the efficacy and safety of COVID-19 mRNA vaccines in cohorts with hematological malignancies compared to healthy controls were systematically searched in four databases. Meta-analysis and subgroup analyses were performed to generate quantitative synthesis. Fifteen studies with 2,055 cohorts with hematological malignancies and 1,105 healthy subjects as control were included. After two doses of COVID-19 vaccination, only 60% of cohorts with hematological malignancies were seroconverted compared to healthy controls (RR 0.60; 95%CI 0.50-0.71). A single dose of the vaccine resulted in a significantly lower seroconversion rate (RR 0.30; 95%CI 0.16-0.54). Non-Hodgkin lymphoma cohorts had the lowest rate of seroconversion (RR 0.5; 95%CI 0.35-0.71) and those who received active treatments had lower immunological responses (RR 0.59; 95%CI 0.46-0.75). Antibody titers were lower in cohorts with hematological malignancies without any differences in adverse effects in both groups. In conclusion, cohorts with hematological malignancies showed a lower seroconversion rate and antibody titers after receiving COVID-19 mRNA vaccines. The type of malignancy and the status of treatment had a significant impact on the response to vaccination. The vaccines were shown to be safe for both patients with hematological malignancies and healthy controls. Booster doses and stricter health protocols might be beneficial for patient populations.

CHARACTERIZING A “N-CoV-2-IgG PS” DIAGNOSTIC KIT TO QUANTIFY SARS-CoV-2 NUCLEOCAPSID PROTEIN-SPECIFIC HUMAN IgG ANTIBODIES.

Confirming detected SARS-CoV-2-specific antibodies is necessary to reveal immune response in COVID-19 convalescent subjects as well as to conduct population studies by screening for specific antibodies to assess rate of COVID-19 prevalence. With this purpose St. Petersburg Pasteur Institute was the first in Russia to develop the ELISA kit for the quantitative determination of human IgG to the SARS-CoV-2 nucleocapsid (N-CoV-2-IgG PS). Arbitrary units (AU/ml) were used to assess the level of antibodies. The data shown in AU/ml were recalculated later to the international units (BAU/ml) in accordance with established the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin. Comparing the data of the N-CoV-2-IgG PS calibration curve with those of the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin revealed a complete inter-assay association (r = 0.999, R² = 0.997) allowing to find that 1BAU/ml = 5.97 AU/ml. The aim of the study was to characterize the “SARSCoV-2 protein N Human IgG Quantitative ELISA Kit” (N-CoV-2-IgG PS), compare quantitative and qualitative data of ELISA kits, assess a correlation between the binding antibodies to SARS-CoV-2 N proteins and the neutralizing antibodies against SARS-CoV-2. The data of correlation analysis of the 83 COVID-19 convalescent blood plasma samples a significant relationship between the antibodies quantitative values and titers SARS-CoV-2-specific antibody (r = 0.8436, R² = 0.7802) as well as a moderate relationship between antibody concentration and positivity index (r = 0.6648, R² = 0.3307), assessed by Chaddock scale. Comparing concentration of N-protein binding antibodies with neutralizing antibody titers level uncovered data consistency obtained by quantitative and virus microneutralization assays (r = 0.7310, R² = 0.6527) used in parallel to analyze 80 blood plasma samples obtained from COVID-19 patients and convalescents. AUC under the ROC curve comprised 0.701 (P < 0.0001) evidencing about a satisfactory informative value for “N-CoV-2-IgG PS” compared with microneutralization assay. In addition, the efficacy of the “N-CoV-2-IgG PS” was 95%, while the positive and negative prognostic value was 97% and 87%, respectively. The data obtained confirmed a correlation between N-protein binding antibody level and neutralizing antibody titer. Checking inter-assay agreement evidenced about acceptance for informativeness and efficacy of using “N-CoV-2-IgG PS”, thereby confirming an opportunity to apply the Kit to screen for SARS-CoV-2 N protein-specific IgG antibody level and assess seroprevalence in diverse population cohorts. (English) [ FROM AUTHOR] Подтверждение наличия антител, специфичных к коронавирусу SARS-CoV-2, важно для выявления иммунного ответа у лиц, переболевших COVID-19, а также для проведения популяционных исследований путем скрининга антител на предмет определения частоты заражения COVID-19. Санкт-Петербургский НИИ эпидемиологии и микробиологии имени Пастера первым в России разработал иммуноферментный набор реагентов «N-CoV-2-IgG PS» для количественного определения IgG человека к нуклеокапсидному белку SARS-CoV-2. Оценка количества антител осуществлялась в условных единицах (УЕ/мл). Ð’ связи с созданием Первого Международного стандарта для количественного определения иммуноглобулинов к SARSCoV-2, нами был проведен пересчет единиц УЕ/мл в международные единицы BAU/мл. Сопоставление калибровочных проб набора с калибровочной кривой Международного стандарта показало полную связь между ними (r = 0,999, R² = 0,997), при этом коэффициент пересчета определен как 1BAU/мл = 5,97 УЕ/мл. Цель данного сообщения — представить характеристики количественного набора реагентов «N-CoV-2- IgG PS», провести сравнение результатов количественного ИФА с качественным ИФА, оценить корреляционную связь между N-антиген-связывающими антителами с SARS-CoV-2-нейтрализующими антителами. Данные корреляционного анализа показали статистически значимую связь между количественными значениями антител и титрами антител (r = 0,8436, R² = 0,7802) и существенное различие между концентрациями антител и значениями индекса позитивности качественного набора (r = 0,6648, R² = 0,3307) при параллельном исследовании 83 образцов плазмы крови пациентов, переболевших COVID-19. Сравнение значений концентраций связывающих антител с титрами нейтрализующих антител показало статистически значимую сопоставимость результатов количественного теста и теста микронейтрализации вируса (r = 0,7310, R² = 0,6527) при параллельном исследовании 80 образцов плазмы крови реконвалесцентов и больных COVID-19. Значение AUC под ROC кривой составило 0,71 (P < 0,0001), что свидетельствует о прием лемой информативности набора «N-CoV-2-IgG PS» по отношению его к тесту микронейтрализации.Эффективность разработанного набора составила 95%, а положительная и отрицательная прогностические ценности составили 97 и 87%. Результаты исследования подтвердили наличие корреляции N-белок-связывающи … антител с титрами нейтрализующих антител. Проверка межтестовой согласованности свидетельствовала о приемлемости показателей информативности и эффективности набора «N-CoV-2-IgG PS», что подтвердило возможность использования его для скрининга IgG-антител и оценки серопревалентности в разных группах населения. (Russian) [ FROM AUTHOR] Copyright of Russian Journal of Infection & Immunity is the property of National Electronic-Information Consortium and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 for patients with breast and gynecological cancer on active anticancer therapy: Results of a prospective observational study.

Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective. Nevertheless, immunocompromised participants were excluded from randomized controlled clinical trials. This study evaluates the efficacy and safety of the Pfizer/BioNTech BNT162b2 (BNT162b2) vaccine in patients with breast and gynecological cancer treated with active anticancer therapy versus a control cohort of healthy participants. Methods: Immune responses to the BNT162b2 vaccine in patients with breast cancer (n = 44) or a gynecological malignancy (n = 6) on active anticancer therapy (28 on chemotherapy, mostly anthracycline- or taxane-based, and 22 on target therapy) and in a control cohort of participants without cancer (n = 67) were investigated by SARS-CoV-2 neutralizing antibody titers measured by S1-binding immunoglobulin G (IgG) concentrations assessed using the LIAISON XL tools (DiaSorin S.p.A.). Response was assessed after a second dose of the BNT162b2 vaccine administered before and at least 3 weeks after the vaccine dose. Results: Overall, 43/50 (86%) patients of the cancer cohort (74% in the breast cancer group and 100% in the gynecological malignancy group) developed IgG antibodies after the second dose of the BNT162b2 vaccine. There were no statistically significant differences in responder rates between patients treated with chemotherapy and those on target therapy. The majority of patients who received chemotherapy with or without target therapy, 21/28 (75%), developed a reliable antibody titer after a vaccine. All seven non-responder patients were undergoing an anthracycline-based regimen. Based on IgG levels (0-400 AU/ml), patients were classified as negative ('non-responders'), weakly positive, or strongly positive ('responders'). No delay in cancer therapy schedule or reported side effects were recorded after BNT162b2 vaccine administration. All healthy participants were strongly positive. Responder rates differed significantly between the two study cohorts (p < 0.001). Conclusions: Most patients develop antibody titers after the second immunization. However, given the persistence of non-responders or weak responders, additional immunization booster seems to be required, along with proactive planning in the vaccination schedule, with vaccine administration spaced out over time with respect to chemotherapy.

Antibody titers and neutralizing activity in cases of COVID-19 after a single dose of vaccination.

Vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy in preventing the onset of disease. However, the immune response to infection immediately after the first vaccination remains unknown. We examined the anti-SARS-CoV-2-binding-antibody titers and neutralizing activity in patients who developed coronavirus disease 2019 after the first vaccination. The amount of anti-SARS-CoV-2-binding antibodies and neutralizing activity drastically increased from the first to the second collection. Our results may provide important data on the course of immune response following vaccination.