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Background: Patients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARSCoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS. Methods: Sera from50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher's exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA. Results: Compared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50 (18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes. Conclusion: Our data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of SARS-CoV2 vaccination in preventing ordinary or intensive care unit (ICU) admissions and deaths among cases registered during a variant transitional pandemic phase in the geographically and culturally unique territory of the Province of Bolzano (South Tyrol), an Italian region with low vaccination coverage. Methods: We collected data from 93,643 patients registered as positive for SARS-CoV-2 by health authorities during the winter of 2021-22. The data were analyzed retrospectively using descriptive statistics and multiple logistic regression. Results: 925 patients were hospitalized (0.99%), 89 (0.10%) were in intensive care, and 194 (0.21%) died. Vaccinated patients had a significantly lower risk of being hospitalized: adjusted Odds Ratio (aOR): 0.39; 95% CI: 0.33-0.46, ICU admission: aOR: 0.16; 95% CI: 0.09-0.29 and death: aOR: 0.41; 95% CI: 0.29-0.58. Similar risk reductions were also observed in booster-vaccinated patients, independent of sex, age, and predominant variant. Furthermore, the median length of stay (LoS) in the ICU was significantly longer for unvaccinated individuals compared to vaccinated subjects (9 vs. 6 days; p < 0.003). Conclusion: Primary series vaccination and ongoing campaign booster doses were effective in preventing all severe disease-related outcomes and in reducing ICU Length of Stay, even during a transitional pandemic phase and in a unique territorial context. [ABSTRACT FROM AUTHOR]

BackgroundPatients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARS-CoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS.MethodsSera from 50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher’s exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA.ResultsCompared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50(18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes.ConclusionOur data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential.

Background: Patients with autoimmune/inflammatory conditions on anti- CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARSCoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients. Methods: We performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV- 2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidicbased immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30). Results: Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7-- 38.8) nM vs. 4.6 (2.3--44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximabtreated patients [median (range) KD: 1.05 (0.45--1.84) nM vs. 20.25 (13.2--38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV- 2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination. Discussion: Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of SARS-CoV2 vaccination in preventing ordinary or intensive care unit (ICU) admissions and deaths among cases registered during a variant transitional pandemic phase in the geographically and culturally unique territory of the Province of Bolzano (South Tyrol), an Italian region with low vaccination coverage.Methods: We collected data from 93,643 patients registered as positive for SARS-CoV-2 by health authorities during the winter of 2021–22. The data were analyzed retrospectively using descriptive statistics and multiple logistic regression.Results: 925 patients were hospitalized (0.99%), 89 (0.10%) were in intensive care, and 194 (0.21%) died. Vaccinated patients had a significantly lower risk of being hospitalized: adjusted Odds Ratio (aOR): 0.39; 95% CI: 0.33–0.46, ICU admission: aOR: 0.16; 95% CI: 0.09–0.29 and death: aOR: 0.41; 95% CI: 0.29–0.58. Similar risk reductions were also observed in booster-vaccinated patients, independent of sex, age, and predominant variant. Furthermore, the median length of stay (LoS) in the ICU was significantly longer for unvaccinated individuals compared to vaccinated subjects (9 vs. 6 days; p < 0.003).Conclusion: Primary series vaccination and ongoing campaign booster doses were effective in preventing all severe disease-related outcomes and in reducing ICU Length of Stay, even during a transitional pandemic phase and in a unique territorial context.

BackgroundPatients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients.MethodsWe performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30).ResultsRituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7–38.8) nM vs. 4.6 (2.3–44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45–1.84) nM vs. 20.25 (13.2–38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination.DiscussionOur results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.

People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4+ and CD8+ T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

Importance: Immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies. Objective: This study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination. Design, setting, and participants: We conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S). Interventions: Intramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up. Main outcomes and measures: The development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated. Results: For the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific Tcellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination. Conclusions: Vaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment. [ABSTRACT FROM AUTHOR]

Immune-responsiveness to SARS-CoV-2 mRNA vaccination is reduced in kidney transplant recipients (KTRs). Previous reports point to a role of mycophenolic acid (MPA). Our observational cohort study included all KTRs at University Hospital Zurich receiving two SARS-CoV-2 mRNA vaccine doses more than 6 months post-transplantation, who were assessed by measuring anti-spike immunoglobulin G (IgG). We applied principles of therapeutic drug monitoring (TDM) to correlate MPA exposure and lymphocyte counts with SARS-CoV-2 IgG. MPA trough levels differ largely among KTRs with a median of 3.1 mg/L (range 0.7-9.5 mg/L). 34 of 84 KTRs (40%) developed positive SARS-CoV-2 IgG after two vaccine doses. KTRs who developed positive SARS-CoV-2 IgG showed significantly higher eGFR (p < 0.001), lower MPA trough levels (p < 0.001) and higher CD19+ lymphocytes (p < 0.001). MPA trough levels <2.5mg/l and CD19+ lymphocytes >40/µl identify KTRs with seroconversion. Upon logistic regression, MPA trough levels <2.5 mg/L were associated with a 7-fold (CI 95%: 1.589-29.934) and ciclosporin use with a 6-fold (CI 95%: 1.148-30.853) increase in the odds of seroconversion. Our study indicates that immune-responsiveness to SARS-CoV-2 mRNA vaccines correlates with MPA exposure measured by MPA trough level but argues against a class effect of MPA. TDM-guided MPA dosing may be a strategy to increase seroconversion rate. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion: Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections. Methods: Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminexbased multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples. Results: All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vectorprimed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified afterOmicron breakthrough infections in parallel to the appearance of new variant-specific antibodies. Discussion: In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration. Methods: To this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups: <40 and =40 years for men, <48 and =48 years for women. Furthermore, results were segregated according to SARS-CoV-2-specific serostatus at baseline. Results: The disaggregated evaluation of humoral responses highlighted antibody levels decreased in older subjects. The humoral responses were higher in females than in males (p=0.002) and previously virus-exposed subjects compared to naïve subjects (p<0.001). The vaccination induced a robust SARS-CoV-2 specific T-cell response at early time points in seronegative subjects compared to baseline levels (p<0.0001). However, a contraction was observed 6 months after vaccination in this group (p<0.01). On the other hand, the pre-existing specific T-cell response detected in natural seropositive individuals was longer-lasting than the response of the seronegative subjects, decreasing only 10 months after vaccination. Our data suggest that Tcell reactiveness is poorly impacted by sex and age. Of note, SARS-CoV-2-specific T-cell response was not correlated to the humoral response at any time point. Discussion: These findings suggest prospects for rescheduling vaccination strategies by considering individual immunization status, personal characteristics, and the appropriate laboratory tests to portray immunity against SARS-CoV-2 accurately. Deepening our knowledge about T and B cell dynamics might optimize the decision-making process in vaccination campaigns, tailoring it to each specific immune response. [ABSTRACT FROM AUTHOR]

ImportanceImmunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies.ObjectiveThis study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination.Design, setting, and participantsWe conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S).InterventionsIntramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up.Main outcomes and measuresThe development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated.ResultsFor the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific T-cellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination.ConclusionsVaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment.

BackgroundVaccination has proven the potential to control the COVID-19 pandemic worldwide. Although recent evidence suggests a poor humoral response against SARS-CoV-2 in vaccinated hematological disease (HD) patients, data on vaccination in these patients is limited with the comparison of mRNA-based, vector-based or inactivated virus-based vaccines.MethodsForty-nine HD patients and 46 healthy controls (HCs) were enrolled who received two-doses complete vaccination with BNT162b2, or AZD1222, or BBIBP-CorV, respectively. The antibodies reactive to the receptor binding domain of spike protein of SARS-CoV-2 were assayed by Siemens ADVIA Centaur assay. The reactive cellular immunity was assayed by flow cytometry. The PBMCs were reactivated with SARS-CoV-2 antigens and the production of activation-induced markers (TNF-α, IFN-γ, CD40L) was measured in CD4+ or CD8+ T-cells ex vivo.ResultsThe anti-RBD IgG level was the highest upon BNT162b2 vaccination in HDs (1264 BAU/mL) vs. HCs (1325 BAU/mL) among the studied groups. The BBIBP-CorV vaccination in HDs (339.8 BAU/mL ***p

IntroductionMany patients with chronic inflammatory dermatosis such as psoriasis usually ask about the safety of COVID-19 vaccination and if it would affect the course of their disease. Indeed, many case reports, case series and clinical studies, reporting psoriasis exacerbation following vaccination against COVID-19, were published during the pandemic. Also, many questions arise regarding the existence of exacerbating factors of these flare ups, including environmental triggers such as the insufficiency of vitamin D levels.MethodsThis is a retrospective study that measures alterations in psoriasis activity and severity index (PASI) not exceeding 2 weeks after the first and second dose of COVID-19 vaccinations in the reported cases and assesses whether such changes have any association with patients’ vitamin D levels. We retrospectively reviewed the case records of all patients with a documented flare up after COVID-19 vaccination in our department as well as those who did not, during a year.ResultsAmong them, we found 40 psoriasis patients that had reported vitamin D levels in the form of 25-hydroxy-vitamin D within 3 weeks after vaccination, including 23 with exacerbation and 17 without exacerbation. Performing χ2 and t-test controls for psoriasis patients with and without flare-ups, a statistically significant dependence emerged in the seasons of summer [χ2(1) = 5.507, p = 0.019], spring [χ2(1) = 11.429, p = 0.001] and in the categories of vitamin D [χ2(2) = 7.932, p = 0.019], while the mean value of vitamin D for psoriasis patients who did not have exacerbation (31.14 ± 6.67 ng/mL) is statistically higher [t(38) = 3.655, p = 0.001] than the corresponding value of psoriasis patients who had an exacerbation (23.43 ± 6.49 ng/mL).DiscussionThis study indicates that psoriasis patients with insufficient (21–29 ng/mL) or inadequate (

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential.Case presentationA 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient’s symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing.ConclusionHypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

IntroductionSARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.MethodsPeripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.ResultsAll individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.DiscussionIn conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.

IntroductionSARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration.MethodsTo this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups:

Introduction: The coronavirus disease 2019 (COVID-19) pandemic impacted how people perform their daily lives in manifold and sometimes massive ways. Particularly, individuals who are at high risk for a severe disease progression, like immunocompromised people, may have experienced drastic changes in social participation during the pandemic. A COVID-19 basic vaccination may have changed the safety behavior of immunocompromised individuals in terms of infection risk and thereby influence social participation and mental wellbeing. Methods: This study aims to investigate self-perceived social participation at baseline before and at follow-up 1 and 6 months after basic vaccination. Beginning in March 2021, 274 immunocompromised persons 18 years or older were enrolled in the COVID-19 Contact Immune study (CoCo study) in Lower Saxony, Germany. Measurements were performed at three time points regarding social participation [Index for the Assessment of Health Impairments (IMET)], mental health [Patient Health Questionnaire-4 (PHQ-4)], subjective health status (five-point Likert-scale) and quality of life (five-point Likert-scale). Results: In total, 126 participants were included in the final analysis. About 60% of the participants showed increasing social participation over time. The greatest increase in social participation was observed within the first month after basic vaccination (p < 0.001). During the following 5 months, social participation remained stable. The domains “social activities,” “recreation and leisure” and “close personal relationships” were responsible for the overall change in social participation. No association was found between social participation and mental health, sociodemographic or medical factors (except hypertension). Discussion: It is unclear why social participation increased after basic vaccination. Perceived vaccine efficacy and a feeling of being protected by the vaccine may have caused relaxed social distancing behaviors. Reducing safety behaviors may, however, increase the risk of a COVID-19 infection for immunocompromised individuals. Further investigations are needed to explore the health-related consequences of more social participation among immunocompromised persons. [ABSTRACT FROM AUTHOR]

BackgroundUnderstanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH).MethodsWe enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models.ResultsThe analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm3 and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively (p-values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively (p-values=0.594, 0.436, 0.706).ConclusionsPLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic impacted how people perform their daily lives in manifold and sometimes massive ways. Particularly, individuals who are at high risk for a severe disease progression, like immunocompromised people, may have experienced drastic changes in social participation during the pandemic. A COVID-19 basic vaccination may have changed the safety behavior of immunocompromised individuals in terms of infection risk and thereby influence social participation and mental wellbeing.MethodsThis study aims to investigate self-perceived social participation at baseline before and at follow-up 1 and 6 months after basic vaccination. Beginning in March 2021, 274 immunocompromised persons 18 years or older were enrolled in the COVID-19 Contact Immune study (CoCo study) in Lower Saxony, Germany. Measurements were performed at three time points regarding social participation [Index for the Assessment of Health Impairments (IMET)], mental health [Patient Health Questionnaire-4 (PHQ-4)], subjective health status (five-point Likert-scale) and quality of life (five-point Likert-scale).ResultsIn total, 126 participants were included in the final analysis. About 60% of the participants showed increasing social participation over time. The greatest increase in social participation was observed within the first month after basic vaccination (p < 0.001). During the following 5 months, social participation remained stable. The domains “social activities,” “recreation and leisure” and “close personal relationships” were responsible for the overall change in social participation. No association was found between social participation and mental health, sociodemographic or medical factors (except hypertension).DiscussionIt is unclear why social participation increased after basic vaccination. Perceived vaccine efficacy and a feeling of being protected by the vaccine may have caused relaxed social distancing behaviors. Reducing safety behaviors may, however, increase the risk of a COVID-19 infection for immunocompromised individuals. Further investigations are needed to explore the health-related consequences of more social participation among immunocompromised persons.

SARS-CoV-2 and its mutant strains continue to rapidly spread with high infection and fatality. Large-scale SARS-CoV-2 vaccination provides an important guarantee for effective resistance to existing or mutated SARSCoV- 2 virus infection. However, whether the host metabolite levels respond to SARS-CoV-2 vaccine-influenced host immunity remains unclear. To help delineate the serum metabolome profile of SARS-CoV-2 vaccinated volunteers and determine that the metabolites tightly respond to host immune antibodies and cytokines, in this study, a total of 59 sera samples were collected from 30 individuals before SARS-CoV-2 vaccination and from 29 COVID-19 vaccines 2 weeks after the two-dose vaccination. Next, untargeted metabolomics was performed and a distinct metabolic composition was revealed between the pre-vaccination (VB) group and two-dose vaccination (SV) group by partial least squares-discriminant and principal component analyses. Based on the criteria: FDR < 0.05, absolute log2 fold change greater than 0.25, and VIP >1, we found that L-glutamic acid, gamma-aminobutyric acid (GABA), succinic acid, and taurine showed increasing trends from SV to VB. Furthermore, SVassociated metabolites were mainly annotated to butanoate metabolism and glutamate metabolism pathways. Moreover, two metabolite biomarkers classified SV from VB individuals with an area under the curve (AUC) of 0.96. Correlation analysis identified a positive association between four metabolites enriched in glutamate metabolism and serum antibodies in relation to IgG, IgM, and IgA. These results suggest that the contents of gamma-aminobutyric acid and indole in serum could be applied as biomarkers in distinguishing vaccinated volunteers from the unvaccinated. What’s more, metabolites such as GABA and taurine may serve as a metabolic target for adjuvant vaccines to boost the ability of the individuals to improve immunity. [ABSTRACT FROM AUTHOR]

Objective: The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. Methods: We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. Results: We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). Interpretation: In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity. [ABSTRACT FROM AUTHOR]

Background: Vaccination against SARS-CoV-2 has been conducted frequently to limit the pandemic but may rarely be associated with postvaccinal autoimmune reactions or disorders. Case presentation: We present a 35-year-old woman who developed fever, skin rash, and headache 2 days after the second SARS-CoV-2 vaccination with BNT162b2 (Pfizer/Biontech). Eight days later, she developed behavioral changes and severe recurrent seizures that led to sedation and intubation. Cerebral magnetic resonance imaging showed swelling in the (para-) hippocampal region predominantly on the left hemisphere and bilateral subcortical subinsular FLAIR hyperintensities. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis of 7 cells/µl and normal protein and immunoglobulin parameters. Common causes of encephalitis or encephalopathy such as viral infections, autoimmune encephalitis with well-characterized autoantibodies, paraneoplastic diseases, and intoxications were ruled out. We made a diagnosis of new-onset refractory status epilepticus (NORSE) due to seronegative autoimmune encephalitis. The neurological deficits improved after combined antiepileptic therapy and immunomodulatory treatment including high-dose methylprednisolone and plasma exchange. Conclusions: Although a causal relationship cannot be established, the onset of symptoms shortly after receiving the SARS-CoV-2 vaccine suggests a potential association between the vaccination and NORSE due to antibody-negative autoimmune encephalitis. After ruling out other etiologies, early immunomodulatory treatment may be considered in such cases. [ABSTRACT FROM AUTHOR]

A molecular mimicry between severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and human proteins supports the possibility that autoimmunity takes place during coronavirus disease 2019 (COVID-19) contributing to tissue damage. For example, antiphospholipid antibodies (aPL) have been reported in COVID-19 as a result of such mimicry and thought to contribute to the immunothrombosis characteristic of the disease. Consistently, active immunization with the virus spike protein may elicit the production of cross-reactive autoantibodies, including aPL. We prospectively looked at the aPL production in healthcare workers vaccinated with RNA- (BNT162b2, n. 100) or adenovirus-based vaccines (ChAdOx1, n. 50). Anti-cardiolipin, anti-beta2 glycoprotein I, anti-phosphatidylserine/prothrombin immunoglobulin G (IgG), IgA, and IgM before and after vaccination were investigated. Anti-platelet factor 4 immunoglobulins were also investigated as autoantibodies associated with COVID-19 vaccination. Additional organ (anti-thyroid) and non-organ (anti-nuclear) autoantibodies and IgG against human proteome were tested as further post-vaccination autoimmunity markers. The antibodies were tested one or three months after the first injection of ChAdOx1 and BNT162b2, respectively; a 12-month clinical follow-up was also performed. Vaccination occasionally induced low titers of aPL and other autoantibodies but did not affect the titer of pre-existing autoantibodies. No significant reactivities against a microarray of approximately 20,000 human proteins were found in a subgroup of ChAdOx1vaccinees. Consistently, we did not record any clinical manifestation theoretically associated with an underlying autoimmune disorder. The data obtained after the vaccination (two doses for the RNA-based and one dose for the adenovirus-based vaccines), and the clinical follow-up are not supporting the occurrence of an early autoimmune response in this cohort of healthcare workers. [ABSTRACT FROM AUTHOR]

Background: Residents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in >70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years. Methods: Peripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2). Results: Our results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups. Conclusions: Our data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5–7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.

During the worldwide ongoing immunization campaign against SARS-CoV-2, growing data on very rare but potentially harmful side effects of such vaccines arise since approval trials have not been adequately powered to detect those events. Besides the already reported vaccine-related myocarditis, which primarily occurs in young male individuals, our attention was recently drawn to a series of older male and female patients, who were referred to our institutions with isolated acute pericarditis without myocardial damage, shortly after SARS-CoV-2 vaccination. We describe a series of five adult patients presenting with chest pain, shortness of breath and isolated pericarditis with and without pericardial effusion after SARS-CoV-2 vaccination. All patients underwent echocardiography and cardiac magnetic resonance, and the corresponding findings, including late gadolinium enhancement (LGE) and T1 and T2 mapping are reported herein. To our knowledge, such cases have not been systematically reported in the current literature so far.

Background:Vaccination against SARS-CoV-2 has been conducted frequently to limit the pandemic but may rarely be associated with postvaccinal autoimmune reactions or disorders.Case presentationWe present a 35-year-old woman who developed fever, skin rash, and headache 2 days after the second SARS-CoV-2 vaccination with BNT162b2 (Pfizer/Biontech). Eight days later, she developed behavioral changes and severe recurrent seizures that led to sedation and intubation. Cerebral magnetic resonance imaging showed swelling in the (para-) hippocampal region predominantly on the left hemisphere and bilateral subcortical subinsular FLAIR hyperintensities. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis of 7 cells/μl and normal protein and immunoglobulin parameters. Common causes of encephalitis or encephalopathy such as viral infections, autoimmune encephalitis with well-characterized autoantibodies, paraneoplastic diseases, and intoxications were ruled out. We made a diagnosis of new-onset refractory status epilepticus (NORSE) due to seronegative autoimmune encephalitis. The neurological deficits improved after combined antiepileptic therapy and immunomodulatory treatment including high-dose methylprednisolone and plasma exchange.ConclusionsAlthough a causal relationship cannot be established, the onset of symptoms shortly after receiving the SARS-CoV-2 vaccine suggests a potential association between the vaccination and NORSE due to antibody-negative autoimmune encephalitis. After ruling out other etiologies, early immunomodulatory treatment may be considered in such cases.

ObjectiveThe pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.MethodsWe here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.ResultsWe show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).InterpretationIn summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

Background and AimThere have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs.MethodsIn this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation.ResultsOf the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10.ConclusionRisk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.

A molecular mimicry between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins supports the possibility that autoimmunity takes place during coronavirus disease 2019 (COVID-19) contributing to tissue damage. For example, anti-phospholipid antibodies (aPL) have been reported in COVID-19 as a result of such mimicry and thought to contribute to the immunothrombosis characteristic of the disease. Consistently, active immunization with the virus spike protein may elicit the production of cross-reactive autoantibodies, including aPL. We prospectively looked at the aPL production in healthcare workers vaccinated with RNA- (BNT162b2, n. 100) or adenovirus-based vaccines (ChAdOx1, n. 50). Anti-cardiolipin, anti-beta2 glycoprotein I, anti-phosphatidylserine/prothrombin immunoglobulin G (IgG), IgA, and IgM before and after vaccination were investigated. Anti-platelet factor 4 immunoglobulins were also investigated as autoantibodies associated with COVID-19 vaccination. Additional organ (anti-thyroid) and non-organ (anti-nuclear) autoantibodies and IgG against human proteome were tested as further post-vaccination autoimmunity markers. The antibodies were tested one or three months after the first injection of ChAdOx1 and BNT162b2, respectively; a 12-month clinical follow-up was also performed. Vaccination occasionally induced low titers of aPL and other autoantibodies but did not affect the titer of pre-existing autoantibodies. No significant reactivities against a microarray of approximately 20,000 human proteins were found in a subgroup of ChAdOx1-vaccinees. Consistently, we did not record any clinical manifestation theoretically associated with an underlying autoimmune disorder. The data obtained after the vaccination (two doses for the RNA-based and one dose for the adenovirus-based vaccines), and the clinical follow-up are not supporting the occurrence of an early autoimmune response in this cohort of healthcare workers.

BackgroundResidents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in >70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years.MethodsPeripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2).ResultsOur results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups.ConclusionsOur data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2.

Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman's rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 – 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 – 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns. [ABSTRACT FROM AUTHOR]

While the global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still ongoing and new virus variants are emerging, there is a universal need for vaccines to protect individuals from severe complications and ideally control the pandemic by enabling herd immunity. Several vaccines against SARS-CoV-2 have been approved and are widely used to stem the recurring waves of coronavirus disease 2019 (COVID-19). Post-marketing surveillance is essential to record even rare safety issues related to these new vaccines. Among these issues, several autoimmune phenomena have been recorded in temporal association with and feasibly triggered by a vaccination. Acquired haemophilia A (AHA) is a rare condition characterized by new-onset haemorrhagic diathesis caused by an inhibitor of blood clotting factor VIII (FVIII), often in the elderly and most commonly associated with autoimmune or malignant disease. There have been a small number of AHA cases triggered by vaccinations, including those against SARS-CoV-2. We report the first case of AHA in temporal association with an mRNA-1273 booster vaccination. The diagnosis was made promptly, and the patient received appropriate care including immunosuppression using glucocorticoids, cyclophosphamide (CYC) and rituximab (RTX). The haemorrhage ceased after escalation of treatment, and the patient is recovering. Concurrent malignancy was initially ruled out using a wide scope of diagnostic tests, but pleomorphic dermal sarcoma (PDS) of the forehead occurred after initiation of specific AHA immunosuppressive treatment. Since large vaccination programs are ongoing worldwide and potential adverse events during post-marketing surveillance have been reported following vaccination against SARS-CoV-2, this case illustrates challenges in rare events occurring in association with SARS-CoV-2 vaccination and to proof a causal relationship. Therefore, there is an urgent need for reporting any events in association with SARS-CoV-2 vaccination, but also a crucial discussion about possible concurrent triggers and follow-up information about individual patients. [ABSTRACT FROM AUTHOR]

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

Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman’s rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 – 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 – 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns.

While the global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still ongoing and new virus variants are emerging, there is a universal need for vaccines to protect individuals from severe complications and ideally control the pandemic by enabling herd immunity. Several vaccines against SARS-CoV-2 have been approved and are widely used to stem the recurring waves of coronavirus disease 2019 (COVID-19). Post-marketing surveillance is essential to record even rare safety issues related to these new vaccines. Among these issues, several autoimmune phenomena have been recorded in temporal association with and feasibly triggered by a vaccination. Acquired haemophilia A (AHA) is a rare condition characterized by new-onset haemorrhagic diathesis caused by an inhibitor of blood clotting factor VIII (FVIII), often in the elderly and most commonly associated with autoimmune or malignant disease. There have been a small number of AHA cases triggered by vaccinations, including those against SARS-CoV-2. We report the first case of AHA in temporal association with an mRNA-1273 booster vaccination. The diagnosis was made promptly, and the patient received appropriate care including immunosuppression using glucocorticoids, cyclophosphamide (CYC) and rituximab (RTX). The haemorrhage ceased after escalation of treatment, and the patient is recovering. Concurrent malignancy was initially ruled out using a wide scope of diagnostic tests, but pleomorphic dermal sarcoma (PDS) of the forehead occurred after initiation of specific AHA immunosuppressive treatment. Since large vaccination programs are ongoing worldwide and potential adverse events during post-marketing surveillance have been reported following vaccination against SARS-CoV-2, this case illustrates challenges in rare events occurring in association with SARS-CoV-2 vaccination and to proof a causal relationship. Therefore, there is an urgent need for reporting any events in association with SARS-CoV-2 vaccination, but also a crucial discussion about possible concurrent triggers and follow-up information about individual patients.

Serious adverse events associated with new vaccines targeting SARS-CoV-2 are of high interest to the public and to public health as a worldwide mass immunization campaign has been initiated to contain the ongoing COVID-19 pandemic. We describe a series of 4 individuals with signs of a myocarditis/pericarditis according to cardiac MRI results in temporal association with currently in the European Union authorized SARS-CoV-2 vaccines. We found mild abnormal MRI results independent of the type of SARS-CoV-2 vaccine. There is a need of continuing monitoring outcomes of myocarditis cases after COVID-19 vaccination as recently published cases suggest an uncomplicated short-term course whereas the long-term implications are not yet known but taking the available evidence into account the benefits of using COVID-19 vaccines still clearly outweigh the risks.

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

Background: The humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs. Materials and Methods: We included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2. Results: 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups. Conclusions: Our study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination. [ABSTRACT FROM AUTHOR]

BackgroundThe COVID-19 pandemic has major implications on kidney transplant recipients (KTRs) since they show increased mortality due to impaired immune responses to SARS-CoV-2 infection and a reduced efficacy of SARS-CoV-2 vaccination. Surprisingly, dialysis patients have shown superior seroconversion rates after vaccination compared to KTRs. Therefore, we investigated peripheral blood B cell (BC) composition before and after kidney transplantation (KT) and aimed to screen the BC compartment to explain impaired antibody generation.MethodsA total of 105 patients were recruited, and multicolor flow cytometric phenotyping of peripheral venous blood BC subpopulations was performed before and 1 year after KT. Complete follow-up was available for 71 individuals. Anti-SARS-CoV-2 antibodies were collected retrospectively and were available for 40 subjects, who had received two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273).ResultsOverall, relative BC frequencies within lymphocytes decreased, and their absolute counts trended in the same direction 1 year after KT as compared to CKD G5 patients. Frequencies and absolute numbers of naïve BCs remained stable. Frequencies of double negative BCs, a heterogeneous subpopulation of antigen experienced BCs lacking CD27 expression, were increased after KT, yet their absolute counts were similar at both time points. Transitional BCs (TrBCs) and plasmablasts were significantly reduced after KT in absolute and relative terms. Memory BCs were affected differently since class-switched and IgM-only subsets decreased after KT, but unswitched and IgD-only memory BCs remained unchanged. CD86+ and CD5+ expression on BCs was downregulated after KT. Correlational analysis revealed that TrBCs were the only subset to correlate with titer levels after SARS-CoV-2 vaccination. Responders showed higher TrBCs, both absolute and relative, than non-responders.ConclusionTogether, after 1 year, KTRs showed persistent and profound compositional changes within the BC compartment. Low TrBCs, 1 year after KT, may account for the low serological response to SARS-CoV-2 vaccination in KTRs compared to dialysis patients. Our findings need confirmation in further studies as they may guide vaccination strategies.

BackgroundA few studies on vaccination in patients with rheumatic diseases, including arthritis, connective tissue diseases, vasculitis, and psoriatic arthropathy (PsA), demonstrated reduced production of neutralizing antibodies to SARS-CoV-2 Spike RBD (receptor-binding domain contained in the N-terminal of the S1 globular head region) when compared to the general population.ObjectiveThe aim of our study was to observe whether different therapies for PsA [methotrexate, anti-TNF antibodies, soluble TNF receptor (etanercept) or IL-17 inhibitors] have a different impact on SARS-CoV-2 vaccination in a homogeneous population of patients.MethodsWe enrolled 110 PsA patients in remission, assessed with Disease Activity in PSoriatic Arthritis (DAPSA). Of these: 63 were in treatment with anti-TNF-α therapy (26 etanercept, 15 certolizumab, 5 golimumab, 17 adalimumab); 37 with anti-IL17 secukinumab; 10 with methotrexate. All patients underwent vaccination for SARS-CoV-2 with mRNA BNT162b2 vaccine. Assessment of absolute and percentage lymphocyte subsets and anti-SARS-CoV-2 Spike RBD IgG antibody value 3 weeks after the second vaccine dose were performed. In addition, the serum antibody levels of 96 healthy healthcare workers (HCW) were analyzed.ResultsThe mean disease activity assessed with DAPSA score was 2.96 (SD = 0.60) with no significant differences between patients under different medications (p = 0.779). Median levels of neutralizing antibodies to SARS-CoV-2 Spike RBD were 928.00 binding antibody unit (BAU)/mL [IQR 329.25, 1632.0]; 1068.00 BAU/ml [IQR 475.00, 1632.00] in patients taking MTX, 846.00 BAU/ml [IQR 125.00, 1632.00] in patients taking etanercept, 908.00 BAU/mL [IQR 396.00, 1632.00] in patients taking anti-IL17 and 1148.00 BAU/ml [IQR 327.00, 1632.00] in patients taking TNF-α inhibitors, without statistically significant differences between these groups. Mean serum antibody level of HCW group was 1562.00 BAU/ml [IQR 975.00, 1632.00], being significantly higher than in the patient group (p = 0.000816). Absolute and percentage count of lymphocyte subsets were not statistically different between the subgroups under different treatments and when compared with HCW.ConclusionsAs for other rheumatic diseases on immunomodulatory treatment, our data showed a reduced humoral response in PsA patients compared to the control group. However, antibody response did not significantly differ between groups treated with different medications.

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.

BackgroundThe humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs.Materials and MethodsWe included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2.Results31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups.ConclusionsOur study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.

Objective: To explore the attitudes and views of patients with inflammatory bowel disease (IBD) on COVID-19 vaccination.Methods: An online interview questionnaire concerning the acceptance or hesitancy toward vaccination for COVID-19 was designed and 543 patients with IBD in China were invited to complete the structured self-administered anonymous questionnaire.Results: Of all the participants, 50.7% were indecisive about the vaccination and only 16.0% opted for it. Vaccination hesitancy was significantly associated with women and those without medical or biomedical backgrounds. The acceptance of COVID-19 vaccination was higher in participants with no history of immune-modifying therapies, especially in those without immunosuppressants. Participants who considered vaccination critically important to self-health or the health of others were more likely to choose immediately or later vaccination. Safety and potential adverse reactions, personal hypoimmunity, efficacy, and reliability of COVID-19 vaccines were the top three concerns of the participants that were independent of their willingness for vaccination.Conclusions: This study discloses the presence of hesitancy for COVID-19 vaccination in patients with IBD. Further studies are warranted to evaluate the efficacy and safety of COVID-19 vaccines in IBD individuals, with a specific focus on the impact of immune-modifying therapies. Health education and recommendation from authoritative sources may facilitate COVID-19 vaccination efforts.

Subacute thyroiditis is an inflammatory thyroid disorder associated with viral infections. Rare cases of subacute thyroiditis have also been described following vaccination. Recently, a few cases of subacute thyroiditis following SARS-CoV-2 vaccination have also been reported. Here, we present two cases of cytological proven subacute thyroiditis after receiving the first dose of a SARS-CoV-2 vaccination. We describe clinical, laboratory, imaging and cytological findings in two cases of subacute thyroiditis that presented in our department 2 weeks after SARS-CoV-2 vaccination with Spikevax (Moderna Biotech, Spain) and Vaxzevria (AstraZeneca; Sweden). Both cases did not have a previous history of thyroid disorders and presented with anterior and lateral neck pain. Clinical test results as well as cytological findings were consistent with subacute thyroiditis. Subacute thyroiditis may develop following a SARS-CoV-2 vaccination and should be considered as a possible side effect in cases that present with thyroid pain.