Comparing Heterologous and Homologous COVID-19 Vaccination: A Longitudinal Study of Antibody Decay.

The humoral response after vaccination was evaluated in 1248 individuals who received different COVID-19 vaccine schedules. The study compared subjects primed with adenoviral ChAdOx1-S (ChAd) and boosted with BNT162b2 (BNT) mRNA vaccines (ChAd/BNT) to homologous dosing with BNT/BNT or ChAd/ChAd vaccines. Serum samples were collected at two, four and six months after vaccination, and anti-Spike IgG responses were determined. The heterologous vaccination induced a more robust immune response than the two homologous vaccinations. ChAd/BNT induced a stronger immune response than ChAd/ChAd at all time points, whereas the differences between ChAd/BNT and BNT/BNT decreased over time and were not significant at six months. Furthermore, the kinetic parameters associated with IgG decay were estimated by applying a first-order kinetics equation. ChAd/BNT vaccination was associated with the longest time of anti-S IgG negativization and with a slow decay of the titer over time. Finally, analyzing factors influencing the immune response by ANCOVA analysis, it was found that the vaccine schedule had a significant impact on both the IgG titer and kinetic parameters, and having a Body Mass Index (BMI) above the overweight threshold was associated with an impaired immune response. Overall, the heterologous ChAd/BNT vaccination may offer longer-lasting protection against SARS-CoV-2 than homologous vaccination strategies.

Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases.

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients.

Dynamics of anti-spike IgG antibody after a third BNT162b2 COVID-19 vaccination in Japanese health care workers.

Objectives: Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity after boosting in East Asia is insufficient. This study aimed to evaluate anti-spike immunoglobulin G [IgG(S)] titers after the third BNT162b2 vaccination. Methods: The dynamics of IgG(S) titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations among the IgG(S) titer, baseline characteristics, and adverse reactions were also evaluated. Results: The geometric mean titer of IgG(S) one month after the third vaccination was 17,400 AU/ml, which increased by approximately 30 times that immediately before the third vaccination. The rate of IgG(S) titer decline was significantly slower after the third vaccination (35.7%) than after the second vaccination (59.1%). The IgG(S) titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the time of vaccination showed significantly higher IgG(S) titers than those without a headache. Conclusions: The IgG(S) titer induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the IgG(S) titer, with a slower rate of decline.

Assessment of early and post COVID-19 vaccination antibody response in healthcare workers: a multicentre cross-sectional study on inactivated, mRNA and vector-based vaccines.

In this multicentre study, we compared the status of antibody production in healthcare personnel (HCP) before and after vaccination using different brands of COVID-19 vaccines between March 2021 and September 2021. Out of a total of 962 HCP enrolled in our study, the antibody against the S1 domain of SARS-CoV-2 was detected in 48.3%, 95.5% and 96.2% of them before, after the first and the second doses of the vaccines, respectively. Our results showed post-vaccination infection in 3.7% and 5.9% of the individuals after the first and second doses of vaccines, respectively. The infection was significantly lower in HCP who presented higher antibody titres before the vaccination. Although types of vaccines did not show a significant difference in the infection rate, a lower infection rate was recorded for AstraZeneca after the second vaccination course. This rate was equal among individuals receiving a second dose of Sinopharm and Sputnik. Vaccine-related side effects were more frequent among AstraZeneca recipients after the first dose and among Sputnik recipients after the second dose. In conclusion, our results showed diversity among different brands of COVID-19 vaccines; however, it seems that two doses of the vaccines could induce an antibody response in most of HCP. The induced immunity could persist for 3-5 months after the second vaccination course.

Evaluation of serological response to anti-SARS-CoV-2 mRNA vaccination in hematological patients.

Introduction: In immunocompromised patients, SARS-CoV-2 mRNA vaccine has been used in Italy from the beginning of the vaccination campaign, but several studies have shown that the serological response of onco-hematological patients was reduced compared to healthy subjects, due to the state of immunosuppression because of both underlying disease and administered therapy. Methods: We evaluated the association of anti-SARS-CoV-2 spike IgG titers in 215 hematological patients with clinical and demographic variables to verify if it was possible to identify predictive parameters of serological response, as well as using a control group, consisting of healthy health workers of San Carlo Hospital in Potenza. Anti-SARS-CoV2 IgG titers were evaluated after 30-45 days post second dose vaccine using chemiluminescent microparticle immunoassay technology. Results: Patients with hematological malignancies, compared with the control arm, had both a mean concentration of anti-SARS-CoV-2 IgG significantly lower and a seroconversion rate numerically lower. All chronic lymphatic leukemia patients showed levels of antibody titer below the mean concentration, also in only clinical surveillance patients. Comparing serological response in hematological malignancies, only acute leukemia patients who were off therapy had the highest seroconversion rate among the patients' cohorts and a mean antibody concentration greater than the control arm. Patients treated with steroids and rituximab showed a lower level of anti-SARS-CoV-2 spike IgG. Differences in anti-spike IgG levels among chronic myeloid leukemia patients stratified according to tyrosine kinase inhibitor therapy and molecular response were observed, and they could have interesting implications on the evaluation of the effects of these drugs on the immune system, but having not reached statistical significance at the moment. The cohort of patients who received a stem cell transplant was very heterogeneous because it included different hematological malignancies and different types of transplant; however, a mean concentration of anti-SARS-CoV2 IgG greater than the control arm was reported. Indeed, among patients who performed a transplant for over 6 months only one had a spike IgG concentration below the cutoff. Conclusions: Our data confirm reduced serological response in hematological patients after anti-SARS-CoV-2 vaccination. However, we found a great diversity of SARS-CoV-2 antibody response according to types of pathologies and therapies.

The IgG glycome of SARS-CoV-2 infected individuals reflects disease course and severity.

Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc region, the structure and possible function of the IgG N-glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19.

Tyrosine Kinase Inhibitors Do Not Promote a Decrease in SARS-CoV-2 Anti-Spike IgG after BNT162b2 Vaccination in Chronic Myeloid Leukemia: A Prospective Observational Study.

We performed a prospective observational study of chronic myeloid leukemia (CML) patients after anti-SARS-CoV-2 BNT162b2 vaccination (VC). In total, 32 CML patients with tyrosine kinase inhibitor (TKI) therapy, 10 CML patients with treatment-free remission, and 16 healthy subjects participated in the study. From April 2021 to September 2021, all cases (median age = 58 years) were vaccinated twice. Immunoglobulin G for SARS-CoV-2 spike protein (S-IgG) was measured at three timepoints (before the first VC, 1-5 weeks after the second VC (T1), and approximately 6 months after the second VC (T2)). S-IgG was not observed before the first VC in any participant. At T1, all cases had acquired S-IgG. There were no significant differences in S-IgG levels among groups. A paired sample comparison of median S-IgG titers between T1 and T2 in all groups showed a significant reduction in T2 S-IgG titers. There were no significant differences in S-IgG levels among groups. When all patients were analyzed, those aged ≥58 years had significantly lower S-IgG levels than those aged <58 years at T1. The BNT162b2 vaccine was highly effective in CML patients with or without TKIs, and S-IgG levels were as persistent as those in healthy individuals.

Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Updated Analysis Involving 22,607 Blood Donors Covering the Period October 2021 to April 2022.

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9-55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8-86.0%) to 95.8% (94.9-96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271-296) to 1437 (1360-1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500-<1000, 1000-<2000, 2000-<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2-19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.

Durability of SARS-CoV-2 Specific IgG Antibody Responses Following Two Doses of Match and Mixed COVID-19 Vaccines Regimens in Saudi Population.

Background: SARS-CoV-2 pandemic continues to threaten the human population with millions of infections and deaths worldwide. Vaccination campaigns undertaken by several countries have resulted in a notable decrease in hospitalization and deaths. However, with the emergence of new virus variants, it is critical to determine the longevity and the protection efficiency provided by the current authorized vaccines. Aim: The aims of this study are to provide data about the magnitude of immune responses in individuals fully vaccinated against COVID-19 in Riyadh province of Saudi Arabia. Also, to evaluate the continuity of specific IgG levels and compare the titers in individuals who have been received two doses of the matched and mixed vaccines, including Pfizer and AstraZeneca against SARS-CoV-2 during the period of three to six months. Moreover, we analyze the current state of immune response in terms of antibody responses in thepopulation postvaccination using homogenous or hetrogenous vaccine regimen. Methods: A total of 141 healthy volunteers were recruited to our study; blood (n=63) and the saliva samples (n=78) and were collected from fully vaccinated individuals in Riyadh city. We employed a specific ELISA assay in plasma and saliva of fully vaccinated individuals. Results: IgG levels varied with age groups with the highest concentration in the age group 19-29 years, but the age group (≥50) had the lowest IgG concentration. The IgG levels in both serum and saliva were higher after three months and start to wane after six months. Individuals who received mixed types of vaccines had significantly better response than Pfizer vaccine alone. Conclusion: The current study investigates the status of humoral responses in different age groups, in terms of antibody measurements. These data will help to evaluate the need for further COVID-19 vaccine doses and to what extent a two-dose regimen will protect vaccinated individuals.

Successful Elimination of SARS-CoV-2 Following Vaccination with BNT162b2 after Prolonged Viral Infection in an Immunocompromised Lymphoma Patient.

A 52-year-old man with mantle cell lymphoma treated with bendamustine and rituximab developed prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite elevated titers of anti-spike IgG antibody, protracted pancytopenia persisted for more than six months. Finally, the anti-SARS CoV-2 vaccine, BNT162b2, was administered, which improved his blood cell count and eliminated the virus. The increased anti-spike IgG titer and lymphocyte count after vaccination suggested that both humoral and cellular immunity acted in coordination to eliminate the virus.

Immunoassay for quantification of antigen-specific IgG fucosylation.

BACKGROUND: Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell FcγRs. Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. METHODS: Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives FcγRIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (FcγR-IgG ELISA). FINDINGS: IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R2=0.93, p < 0.0001). The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. INTERPRETATION: FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to FcγR in a high-throughput manner accessible to all diagnostic and research laboratories. FUNDING: This work was funded by the Stichting Sanquin Bloedvoorziening (PPOC 19-08 and SQI00041) and ZonMW 10430 01 201 0021.

Antibody response with SARS-CoV-2 inactivated vaccine (CoronaVac) in Turkish geriatric population.

BACKGROUND: Sars-CoV-2 infection influences older individuals at the forefront, and there is still limited data on the COVID-19 vaccine response in the geriatric population. This study aimed to assess antibody response after vaccination with SARS-CoV-2 inactivated vaccine and examine possible factors affecting this response in a geriatric population. METHODS: individuals who have been on at least the 28th day after the second dose of the COVID-19 vaccine were included. Comprehensive geriatric assessment tools and the Clinical Frailty Scale were performed. SARS-CoV-2 spike-specific IgG antibodies were detected and, levels ≥1 U/ml were defined as seropositive, <1 U/ml were defined as seronegative. RESULTS: a total of 497 patients were included and divided into three groups according to the days past after the second dose of the vaccine (Group 1: 28-59 days, Group 2: 60-89 days and Group 3: 90 days and more). Groups included 188, 148 and 171 patients, respectively. Seropositivity rate in each group was 80.9,73.2 and 57.3%, respectively. In Groups 1 and 2, Charlson Comorbidity Index score was higher in the seronegative group (P = 0.023 and P = 0.011, respectively). In Group 3, the prevalence of frailty was significantly higher in the seronegative group (P = 0.002). CONCLUSION: to the best of our knowledge, this is the first study assessing the antibody response after vaccination with Sars-CoV 2 inactivated vaccine in the Turkish geriatric population. Moreover, this is the first study revealing the relationship between antibody response and frailty. Larger studies are needed to confirm the antibody response duration and the association between frailty and COVID-19 vaccine response.

Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19.

BACKGROUND: Immunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19. METHODS: In this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography-mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected hospitalized patients. FINDINGS: At baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers. INTERPRETATION: Association of low galactosylation, sialylation as well as high bisection with disease severity and inflammatory markers suggests that further studies are needed to understand how anti-S IgG1 glycosylation may contribute to disease mechanism and to evaluate its biomarker potential. FUNDING: This project received funding from the European Commission's Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund.

The association between adverse reactions and immune response against SARS-CoV-2 spike protein after vaccination with BNT162b2 among healthcare workers in a single healthcare system: a prospective observational cohort study.

Adverse reactions after vaccination with COVID-19 mRNA vaccines are common; however, the association between adverse reactions and humoral responses is uncertain. To determine whether humoral immune responses after BNT162b2 vaccine administration were associated with local and systemic adverse reactions, we conducted a prospective observational cohort study in a single tertiary referral center. Healthcare workers who received the first dose of BNT162b2 vaccine were recruited. SARS-CoV-2 anti-spike IgG antibody titers were measured three weeks after the second dose and information about adverse reactions after vaccination was collected. Among the 887 participants, 641 (72.3%) were women. The median age was 38 (range, 22-74) years. All but one showed anti-spike IgG levels well above the cutoff, with a median level of 13,600 arbitrary units/mL. Overall, 800 (92.2%) participants reported some reactions after the first dose and 822 (96.3%) after the second dose. Significantly more participants reported systemic reactions after the second dose than after the first dose (P < .01), and 625 (73.6%) reported that reactions were stronger after the second dose. Factors positively associated with elevation of anti-spike IgG levels were history of asthma (24% higher if present, P = .01) and stronger reactions after the second dose (19% higher if experienced, P = .02). The majority of participants showed good humoral responses and reported some adverse reactions after vaccination. Anti-spike IgG levels were significantly higher if adverse reactions after the second dose were stronger than those after the first dose. These findings may help inform current and future vaccine recipients.

Longitudinal Humoral and Cellular Immune Responses Following SARS-CoV-2 Vaccination in Patients with Myeloid and Lymphoid Neoplasms Compared to a Reference Cohort: Results of a Prospective Trial of the East German Study Group for Hematology and Oncology (OSHO).

PURPOSE: To assess humoral responses longitudinally and cellular immunogenicity following SARS-CoV-2-vaccination in patients with hematologic and oncologic malignancies receiving checkpoint-inhibitors. METHODS: This prospective multicenter trial of the East-German-Study-Group-for-Hematology-and-Oncology, enrolled 398 adults in a two (patients; n = 262) to one (controls; n = 136) ratio. Pre-vaccination, day 35 (d35), and day 120 (d120) blood samples were analyzed for anti-spike antibodies and d120 IL-2+IFNγ+TNFα+-CD4+- and CD8+-cells. Laboratories were blinded for patients and controls. RESULTS: Patients belonged to the myeloid (n = 131), lymphoid (n = 104), and checkpoint-inhibitor (n = 17) cohorts. While d35 seroconversion was higher in controls (98%) compared to patients (68%) (p < 0.001), d120 seroconversion improved across all patient cohorts [checkpoint-inhibitors (81% to 100%), myeloid (82% to 97%), lymphoid (48% to 66%)]. CD4+- and CovCD8+-cells in the lymphoid (71%/31%) and control (74%/42%) cohorts were comparable but fewer in the myeloid cohort (53%, p = 0.003 /24%, p = 0.03). In patients with hematologic malignancies, no correlation between d120 humoral and cellular responses was found. A sizeable fraction of lymphoid patients demonstrated T-cell responses without detectable spike-specific-IgGs. CONCLUSIONS: Evidence of vaccine-elicited humoral and/or cellular immunogenicity in most patients is provided. Both humoral and cellular responses are crucial to determine which patients will generate/maintain immunity. The findings have implications on public health policy regarding recommendations for SARS-CoV-2 booster doses.

Dynamics of anti-Spike IgG antibody level after the second BNT162b2 COVID-19 vaccination in health care workers.

INTRODUCTION: Many countries are administering a third dose of COVID-19 vaccines, but the evaluation of vaccine-induced immunity is insufficient. In addition, there are few reports of long-term observation of anti-spike IgG antibody titers after the vaccination in the Japanese population. This study aimed to evaluate anti-spike IgG levels in the Japanese health care workers six months after the BNT162b2 vaccination. METHODS: Dynamics of anti-spike IgG levels were assessed over a six-month period following the second vaccination in 49 participants (Analysis-1). A cross-sectional assessment of anti-spike IgG levels six months after the second vaccination was performed in 373 participants (Analysis-2). RESULTS: In Analysis-1, the geometric mean titer of anti-spike IgG was lower in the older age group and decreased consistently after the second vaccination regardless of age. In Analysis-2, the anti-spike IgG level was significantly negatively associated with age (r = -0.35, p < 0.01). This correlation remained statistically significant (r = -0.28, p < 0.01) after adjustment for sex, BMI, smoking habits, alcohol drinking habits, allergies, and fever or other adverse reactions at the time of vaccination. Additionally, participants who drank alcohol daily had significantly lower anti-spike IgG levels than participants who had never drunk alcohol. Sex, smoking habits, allergy, and fever and other side effects after vaccination did not show a significant association with anti-spike IgG levels. CONCLUSIONS: Six months post-vaccination, the anti-spike IgG level was substantially lower in older persons and daily alcohol drinkers. This may be an indication for an additional vaccine dose for these at-risk categories.

A case report of breakthrough infection with the SARS-CoV-2 delta variant and household transmission: Role of vaccination, anti-spike IgG and neutralizing activity.

There have been several reports of breakthrough infections, which are defined as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among individuals who had received at least two doses of vaccine at least 14 days before the onset of infection, but data on the antibody titers, including SARS-CoV-2 neutralizing antibody activity, and the clinical course of individuals with breakthrough infections are limited. We encountered a case of breakthrough infection with the SARS-CoV-2 delta variant in a 31-year-old female healthcare worker (the index case, Case 1) and a secondary case (Case 2) in her unvaccinated 33-year-old husband. We studied the role of the anti-spike immunoglobulin G (IgG) and neutralizing antibody activity in the two case patients. Case 1 had high anti-spike IgG detected on day 3 of the illness, with low neutralizing antibody activity. The neutralizing antibody activity started to increase on day 5 of the illness. In Case 2 both the anti-spike IgG and the neutralizing antibody activity remained low from days 4-11 of illness, and the anti-spike IgG gradually increased from day 9. In Case 1, the fever broke within 4 days of onset, coinciding with the rise in neutralizing antibodies, whereas the fever took 7 days to resolve in Case 2. SARS-CoV-2 infection can occur even in vaccinated individuals, but vaccination may contribute to milder clinical symptoms because neutralizing antibodies are induced earlier in vaccinated individuals than in unvaccinated individuals.

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up.

To investigate the dynamic association among binding and functional antibodies in health-care-workers receiving two doses of BNT162b2 mRNA COVID-19-vaccine, SARS-CoV-2 anti-RBD IgG, anti-Trimeric-S IgG, and neutralizing antibodies (Nabs) were measured in serum samples collected at 2 weeks, 3 months, and 6 months from full vaccination. Despite the high correlation, results for anti-RBD and anti-Trimeric S IgG were numerically different even after recalculation to BAU/mL following WHO standards indications. Moreover, after a peak response at 2 weeks, anti-RBD IgG levels showed a 4.5 and 13 fold decrease at 3 and 6 months, respectively, while the anti-Trimeric S IgG presented a less pronounced decay of 2.8 and 4.7 fold. Further different dynamics were observed for Nabs titers, resulting comparable at 3 and 6 months from vaccination. We also demonstrated that at NAbs titers ≥40, the area under the receiver operating characteristic curve and the optimal cutoff point decreased with time from vaccination for both anti-RBD and anti-Trimeric S IgG. The mutating relation among the anti-RBD IgG, anti-Trimeric S IgG, and neutralizing antibodies are indicative of antibody maturation upon vaccination. The lack of standardized laboratory procedures is one factor interfering with the definition of a correlate of protection from COVID-19.

Assessing humoral immune response after two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthcare workers.

OBJECTIVES: During COVID-19 pandemic, the absence of immunity in the population left them susceptible to infection with SARS-CoV-2; healthcare workers (HCWs) being in the highest risk group. This study intends to assess and follow up the humoral immunity in HCWs vaccinated with an inactive virus vaccine (CoronaVac). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 1072 HCWs were investigated for the presence of immunoglobulin G antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2 after vaccination. Blood samples were obtained after 28 days of the first dose, 21 days of the second dose, and 3 months after the second dose. Detection of antispike antibodies was performed by the chemiluminescent microparticle immunoassay method (SARS-CoV-2 IgG II Quant, Abbott, Ireland). The results greater than or equal to the cutoff value of 50.0 AU/mL were reported as positive. RESULTS: Four weeks after the first dose of vaccine, antispike antibodies were detected in 834/1072 (77.8%) of HCWs. Seropositivity was higher among females (84.6%) than males (70.6% p < 0.001) and was found to be highest in both women and men between the ages of 18-34 years. Antispike antibodies were detected in 1008 of 1012 (99.6%) after 21 days of the second dose and in 803 of 836 (96.1%) after 3 months of the second dose. CONCLUSIONS: CoronaVac was found to be highly immunogenic after two consecutive doses performed 28 days apart to HCWs; however, the immunogenicity declined significantly (p < 0.001) after 3 months following the second dose of vaccine.

Outbreak of SARS-CoV-2 B.1.617.2 (delta) variant in a nursing home 28 weeks after two doses of mRNA anti-COVID-19 vaccines: evidence of a waning immunity.

OBJECTIVES: To describe a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) variant outbreak among residents (n = 69) and health workers (n = 69) of a small nursing home in northeastern Italy, with full vaccination coverage of 91% and 82%, respectively. Evaluation of the anti-Spike IgG titres 28 weeks after the mRNA vaccine booster dose against SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Sera were collected within 48 hours from the index case; anti-Spike IgG was determined (expressed as WHO binding antibody units (BAU)/mL) through a commercial quantitative assay; SARS-CoV-2 was diagnosed using RT-PCR, and full-genome sequencing was performed for lineage characterization. Residents were grouped according to anti-Spike IgG titres (≤50, 51-1000 and > 1000 BAU/mL) and the resulting protection against infection and severe disease was measured. RESULTS: None of the health workers and 14 of the 59 (24%) residents fully vaccinated and without a previous SARS-CoV-2 infection showed anti-Spike IgG ≤50 BAU/mL (one-sided Fisher exact test, p 0.011). Among these residents, a level of anti-Spike IgG ≤50 BAU/mL resulted in a higher risk of SARS-CoV-2 infection (relative risk 1.55, 95% CI 1.17-2.05) and severe COVID-19 (relative risk 5.33, 95% CI 1.83-15.57). CONCLUSION: Low levels of SARS-CoV-2 neutralizing anti-Spike IgG in serum 28 weeks after the administration of the second dose parallel the waning of vaccine protection.