Patients with type 2 diabetes mellitus present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to healthy subjects: a prospective cohort study.

AIM: To compare the kinetics of neutralizing antibodies (NΑbs) against SARS-CoV-2 after vaccination with the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with T2DM and healthy controls. METHODS: NAb levels after the BNT162b2 mRNA vaccine were compared between 50 patients with non-insulin treated T2DM and 50 age-, gender-, and BMI-matched healthy controls up to 3 months after the second dose. The median age of both groups was 70 years. RESULTS: On day 1, mean NAbs of the control and T2DM groups were 14.64% (standard error, SE = 2.30) and 14.04% (SE = 2.14), respectively (p value = 0.926). Three weeks later, the mean NAb values were 39.98% (SE = 3.53) in the control group and 40.97% (SE = 3.99) in participants with T2DM (p value = 0.698). One month after the second vaccination, mean NAb values increased to 87.13% (SE = 2.94) in the control group and 89.00% (SE = 2.18) in the T2DM group. Three months after the second vaccine dose, the mean inhibitory titers decreased to 83.49% (SE = 3.82) (control group) and 76.36% (SE = 3.33) (T2DM group). On all occasions, no significant difference was found between the two groups (all p values > 0.05). CONCLUSIONS: Patients with T2DM present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to that of healthy subjects.

Clinical usefulness of testing for severe acute respiratory syndrome coronavirus 2 antibodies.

In the COVID-19 pandemic era, antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven an invaluable tool and herein we highlight some of the most useful clinical and/or epidemiological applications of humoral immune responses recording. Anti-spike circulating IgGs and SARS-CoV-2 neutralizing antibodies can serve as predictors of disease progression or disease prevention, whereas anti-nucleocapsid antibodies can help distinguishing infection from vaccination. Also, in the era of immunotherapies we address the validity of anti-SARS-CoV-2 antibody monitoring post-infection and/or vaccination following therapies with the popular anti-CD20 monoclonals, as well as in the context of various cancers or autoimmune conditions such as rheumatoid arthritis and multiple sclerosis. Additional crucial applications include population immunosurveillance, either at the general population or at specific communities such as health workers. Finally, we discuss how testing of antibodies in cerebrospinal fluid can inform us on the neurological complications that often accompany COVID-19.

Second Booster BNT162b2 Restores SARS-CoV-2 Humoral Response in Patients With Multiple Myeloma, Excluding Those Under Anti-BCMA Therapy.

COVID-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (MM) compared with healthy individuals, whereas the SARS-CoV-2-specific immunity fades over time. The purpose of this study was to explore the kinetics of SARS-CoV-2 neutralizing antibodies (NAbs) in patients with MM after vaccination with the BNT162b2 mRNA vaccine, focusing on their response before (B4D) and at 1 month after the fourth vaccination (M1P4D). Overall, 201 patients with a median age of 67 years were included, whereas 114 (56.7%) were men. The median NAbs levels B4D were 80.0% (±3.5%) and at M1P4D they increased to a median value of 96.1% (±3.7%). The NAb values at M1P4D were similar to those at 1 month post the third dose and superior to all previous timepoints. At M1P4D, the NAbs levels of all the treatment groups increased, apart from the anti-BCMA group. A significant increase in median NAbs values was observed for those receiving CD38-based treatment (n = 43, from 71.0% B4D to 96.0% at M1P4D) and those who did not receive CD38- or BCMA-targeted therapy (n = 137, from 89.6% B4D to 96.3% at M1P4D). Regarding the patients under BCMA-based therapy (n = 21), there was no remarkable increase in NAbs values following the second booster shot (from 3.0% B4D to 4.0% at M1P4D). In conclusion, booster vaccination with the BNT162b2 results in a substantially improved humoral response against SARS-CoV-2 in patients with MM. Anti-BCMA treatment remains an adverse predictive factor for NAbs response; thus, tailored prevention measures should be considered for this patient subgroup.

Assessment of Postvaccination Neutralizing Antibodies Response against SARS-CoV-2 in Cancer Patients under Treatment with Targeted Agents.

The administration of a third dose of a vaccine against SARS-CoV-2 has increased protection against disease transmission and severity. However, the kinetics of neutralizing antibodies against the virus has been poorly studied in cancer patients under targeted therapies. Baseline characteristics and levels of neutralizing antibodies at specific timepoints after vaccination were compared between patients suffering from breast, ovarian or prostate cancer and healthy individuals. Breast cancer patients were treated with cyclin D kinase 4/6 inhibitors and hormonal therapy, ovarian cancer patients were treated with poly (ADP-ribose) polymerase inhibitors and prostate cancer patients were treated with an androgen receptor targeted agent. Levels of neutralizing antibodies were significantly lower in cancer patients compared to healthy individuals at all timepoints. Antibodies' titers declined over time in both groups but remained above protective levels (>50%) at 6 months after the administration of the second dose. The administration of a third dose increased neutralizing antibodies' levels in both groups. The titers of protective against SARS-CoV-2 antibodies wane over time and increase after a third dose in cancer patients under treatment.

SARS-CoV-2 humoral responses following booster BNT162b2 vaccination in patients with B-cell malignancies.

Patients with B-cell malignancies have suboptimal immune responses to SARS-CoV-2 vaccination and are a high-risk population for severe COVID19 disease. We evaluated the effect of a third booster BNT162b2 vaccine on the kinetics of anti- SARS-CoV-2 neutralizing antibody (NAbs) titers in patients with B-cell malignancies. Patients with NHL (n = 54) Waldenström's macroglobulinemia (n = 90) and chronic lymphocytic leukemia (n = 49) enrolled in the ongoing NCT04743388 study and compared against matched healthy controls. All patient groups had significantly lower NAbs compared to controls at all time points. 1 month post the third dose (M1P3D) NAbs increased significantly compared to previous time points (median NAbs 77.9%, p < .05 for all comparisons) in all patients. NAbs ≥ 50% were seen in 59.1% of patients, 34.5% of patients with suboptimal responses post-second dose, elicited a protective NAb titer ≥50%. Active treatment, rituximab, and BTKi treatment were the most important prognostic factors for a poor NAb response at 1MP3D; only 25.8% of patients on active treatment had NAbs ≥ 50%. No significant between-group differences were observed. Patients with B-cell malignancies have inferior humoral responses against SARS-CoV-2 and booster dose enhances the NAb response in a proportion of these patients.

SARS-CoV-2 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition.

Considering that COVID-19 could adversely affect cancer patients, several countries have prioritized this highly susceptible population for vaccination. Thus, rapidly generating evidence on the efficacy of SARS-CoV-2 vaccination in the subset of patients with cancer under active therapy is of paramount importance. From this perspective, we launched the present prospective observational study to comprehensively address the longitudinal dynamics of immunogenicity of both messenger RNA (mRNA) and viral vector-based vaccines in 85 patients treated with immune checkpoint inhibitors (ICIs) for a broad range of solid tumors. Despite the relatively poor humoral responses following the priming vaccine inoculum, the seroconversion rates significantly increased after the second dose. Waning vaccine-based immunity was observed over the following six months, yet the administration of a third booster dose remarkably optimized antibody responses. Larger cohort studies providing real-world data with regard to vaccines effectiveness and durability of their protection among cancer patients receiving immunotherapy are an increasing priority.

Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis.

Vaccination is a major tool for mitigating the coronavirus disease 2019 (COVID-19) pandemic, and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a proinflammatory action of the lipid nanoparticles used or the delivered mRNA (i.e., the vaccine formulation), as well as to the unique nature, expression pattern, binding profile, and proinflammatory effects of the produced antigens - spike (S) protein and/or its subunits/peptide fragments - in human tissues or organs. Current knowledge on this topic originates mostly from cell-based assays or from model organisms; further research on the cellular/molecular basis of the mRNA vaccine-induced AEs will therefore promise safety, maintain trust, and direct health policies.

Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study.

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.

Oxidative stress and endogenous DNA damage in blood mononuclear cells may predict anti-SARS-CoV-2 antibody titers after vaccination in older adults.

Immune senescence in the elderly has been associated with chronic oxidative stress and DNA damage accumulation. Herein we tested the hypothesis that increased endogenous DNA damage and oxidative stress in peripheral blood mononuclear cells of older adults associate with diminished humoral immune response to SARS-CoV-2 vaccination. Increased oxidative stress and DNA double-strand breaks (DSBs) were detected in 9 non-immunocompromised individuals aged 80-96 years compared to 11 adults aged 27-44 years, before, as well as on days 1 and 14 after the first dose, and on day 14 after the second dose of the BNT162B2-mRNA vaccine (all p < 0.05). SARS-CoV-2 vaccination induced a resolvable increase in oxidative stress and DNA damage, but individual DSB-repair efficiency was unaffected by vaccination irrespective of age, confirming vaccination safety. Individual titers of anti-Spike-Receptor Binding Domain (S-RBD)-IgG antibodies, and the neutralizing capacity of circulating anti-SARS-CoV-2 antibodies, measured on day 14 after the second dose in all participants, correlated inversely with the corresponding pre-vaccination endogenous oxidative stress and DSB levels (all p < 0.05). In particular, a strong inverse correlation of individual pre-vaccination DSB levels with both the respective anti-S-RBD-IgG antibodies titers (r = -0.867) and neutralizing capacity of circulating anti-SARS-CoV-2 antibodies (r = -0.983) among the 9 older adults was evident. These findings suggest that humoral responses to SARS-CoV-2 vaccination may be weaker when immune cells are under oxidative and/or genomic stress. Whether such measurements may serve as biomarkers of vaccine efficacy in older adults warrants further studies.

Immune response and adverse events after vaccination against SARS-CoV-2 in adult patients with transfusion-dependent thalassaemia.

Patients with transfusion-dependent thalassaemia (TDT) are considered an at increased-risk population for severe and/or morbid coronavirus disease 2019 (COVID-19) infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions after vaccination have been reported, with severe ones being extremely rare. Patients with TDT may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. Here, we show that adult patients with TDT following vaccination with the novel messenger RNA vaccines have mild adverse events and can produce protective antibodies comparable to the healthy population.

Comparison of Neutralizing Antibody Responses at 6 Months Post Vaccination with BNT162b2 and AZD1222.

Along with their level of protection against COVID-19, SARS-CoV-2-specific antibodies decline over time following vaccination with BNT162b2. However, relevant data on AZD1222 are scarce. In this context, the aim of this study was to compare SARS-CoV-2 neutralizing antibody (NAb) levels at one, three and six months after second vaccination with the BNT162b2 mRNA vaccine and the ChAdOx1 (AZD1222) viral vector vaccine (NCT04743388). The measurements were performed with the GenScript's cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ, USA). Overall, data from 282 individuals were included (BNT162b2 n = 83, AZD1222 n = 199). Both vaccines induced strong NAbs responses at 1 month following vaccination. Interestingly, NAb activity seemed superior with BNT162b2 compared with AZD1222. A gradual decline in NAbs titers was evident at 3 and 6 months post vaccination with both vaccines. However, the superiority of NAb response with BNT162b2 over AZD1222 remained consistent at all time points examined. Furthermore, the elimination rate of the NAb titer was higher throughout during the study period for those vaccinated with AZD1222 compared with BNT162b2. Age, gender, body mass index or comorbidities did not have a significant impact on NAbs levels over time. Our results may inform public health policies regarding the timing of booster COVID-19 vaccine shots.

Predictive Factors for Neutralizing Antibody Levels Nine Months after Full Vaccination with BNT162b2: Results of a Machine Learning Analysis.

Vaccination against SARS-CoV-2 with BNT162b2 mRNA vaccine plays a critical role in COVID-19 prevention. Although BNT162b2 is highly effective against COVID-19, a time-dependent decrease in neutralizing antibodies (NAbs) is observed. The aim of this study was to identify the individual features that may predict NAbs levels after vaccination. Machine learning techniques were applied to data from 302 subjects. Principal component analysis (PCA), factor analysis of mixed data (FAMD), k-means clustering, and random forest were used. PCA and FAMD showed that younger subjects had higher levels of neutralizing antibodies than older subjects. The effect of age is strongest near the vaccination date and appears to decrease with time. Obesity was associated with lower antibody response. Gender had no effect on NAbs at nine months, but there was a modest association at earlier time points. Participants with autoimmune disease had lower inhibitory levels than participants without autoimmune disease. K-Means clustering showed the natural grouping of subjects into five categories in which the characteristics of some individuals predominated. Random forest allowed the characteristics to be ordered by importance. Older age, higher body mass index, and the presence of autoimmune diseases had negative effects on the development of NAbs against SARS-CoV-2, nine months after full vaccination.