Search

Objective: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. Methods: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell's palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines. Results: The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51–7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02–3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08–2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96–1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48–3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20–2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67–3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98–1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations. Discussion: This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine. [ABSTRACT FROM AUTHOR]

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination. [ABSTRACT FROM AUTHOR]

Objective: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. Methods: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell’s palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines. Results: The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51–7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02–3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08–2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96–1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48–3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20–2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67–3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98–1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations. Discussion: This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine.

This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5–7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark. [ABSTRACT FROM AUTHOR]

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization. [ABSTRACT FROM AUTHOR]

Introduction: Vaccination is one of the best strategies to control coronavirus disease 2019 (COVID-19), and multiple vaccines have been introduced. A variety of neurological adverse effects have been noted after the implementation of large-scale vaccination programs. Methods: We reported two rare cases of possible mRNA-1273 vaccine-induced acute encephalitis, including clinical manifestations, laboratory characteristics, and management. Results: The clinical manifestations might be related to hyperproduction of systemic and cerebrospinal fluid (CSF) cytokines. mRNA vaccines are comprised of nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA, which is translated into SARS-CoV-2 spike protein by the host's ribosomes, activating the adaptive immune response. Exposed mRNA or vaccine components may also be detected as antigens, further resulting in aberrant proinflammatory cytokine cascades and activation of immune signaling pathways. Both patients exhibited significant clinical improvement after a course of steroid therapy. Conclusions: The use of COVID-19 vaccines to prevent and control SARS-CoV-2 infections and complications is the most practicable policy worldwide. However, inaccurate diagnosis or other diagnostic delays in cases of vaccine-induced acute encephalitis may have devastating and potentially life-threatening consequences for patients. Early diagnosis and timely treatment can result in a favorable prognosis. [ABSTRACT FROM AUTHOR]

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

Although numerous COVID-19 vaccines are effective against COVID-19 infection and variants of concern (VOC) in the real world, it is imperative to obtain evidence of the corresponding vaccine effectiveness (VE). This study estimates the real-world effectiveness of the BNT162b2 and mRNA-1273 vaccines against COVID-19 infection and determines the influence of different virus variants on VE by using test-negative design (TND) studies. We systematically searched for published articles on the efficacy of BNT162b2 and mRNA-1273 against COVID-19 infection. Two researchers independently selected and extracted data from eligible studies. We calculated the VE associated with different vaccine types, SARS-CoV-2 variants, and vaccination statuses, using an inverse variance random-effects model. We selected 19 eligible studies in the meta-analysis from 1651 records. For the partially vaccinated group, the VE of BNT162b2 and mRNA-1273 was 61% and 78% against COVID-19 infection, respectively. For the completely vaccinated group, the VE of BNT162b2 and mRNA-1273 was 90% and 92% against COVID-19 infection, respectively. During subgroup analyses, the overall VE of BNT162b2 and mRNA-1273 against the Delta variant was 53% and 71%, respectively, for the partially vaccinated group; the respective VE values were 85% and 91% for the fully vaccinated group. Irrespective of the BNT162b2 or mRNA-1273 vaccines, the Delta variant significantly weakened vaccine protection for the partially vaccinated group, while full vaccination was highly effective against COVID-19 infection and various VOC. The mRNA-1273 vaccine is more effective against COVID-19 infection and VOC than the BNT162b2 vaccine, especially for the partially vaccinated group. Overall, the results provide recommendations for national and regional vaccine policies. [ABSTRACT FROM AUTHOR]

The vaccines designed against the SARS-CoV-2 coronavirus are based on the spike (S) protein. Processing of the S protein by antigen-presenting cells (APC) and its subsequent presentation to T cells is an essential part of the development of a humoral response. HLA-class II alleles are considered immune response genes because their codified molecules, expressed on the surface of APCs (macrophages, dendritic, and B cells) present antigenic peptides to T cell via their T cell receptor (TCR). The HLA-class II genes are highly polymorphic, regulating what specific peptides induce follicular helper T cells (TFH) and promote B lymphocyte differentiation into plasma or memory B cells. This work hypothesizes that the presence of certain HLA-class II alleles could be associated with the intensity of the humoral response (amount, length) to the SARS-CoV2 mRNA 1273 vaccine. We have studied the relationship between the HLA-class II typing of 87 health workers and the level of antibodies produced 30 days after vaccination. We show a possible association between the HLA-DRB1* 07:01 allele and the HLA-DRB1*07:01~DQA1*02:01~DQB1*02:02 haplotype to a higher production of antibodies 30 days after the administration of the second dose of mRNA-1273. [ABSTRACT FROM AUTHOR]

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines. [ABSTRACT FROM AUTHOR]

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization.

This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5–7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

Introduction: Vaccination is one of the best strategies to control coronavirus disease 2019 (COVID-19), and multiple vaccines have been introduced. A variety of neurological adverse effects have been noted after the implementation of large-scale vaccination programs. Methods: We reported two rare cases of possible mRNA-1273 vaccine-induced acute encephalitis, including clinical manifestations, laboratory characteristics, and management. Results: The clinical manifestations might be related to hyperproduction of systemic and cerebrospinal fluid (CSF) cytokines. mRNA vaccines are comprised of nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA, which is translated into SARS-CoV-2 spike protein by the host’s ribosomes, activating the adaptive immune response. Exposed mRNA or vaccine components may also be detected as antigens, further resulting in aberrant proinflammatory cytokine cascades and activation of immune signaling pathways. Both patients exhibited significant clinical improvement after a course of steroid therapy. Conclusions: The use of COVID-19 vaccines to prevent and control SARS-CoV-2 infections and complications is the most practicable policy worldwide. However, inaccurate diagnosis or other diagnostic delays in cases of vaccine-induced acute encephalitis may have devastating and potentially life-threatening consequences for patients. Early diagnosis and timely treatment can result in a favorable prognosis.

The vaccines designed against the SARS-CoV-2 coronavirus are based on the spike (S) protein. Processing of the S protein by antigen-presenting cells (APC) and its subsequent presentation to T cells is an essential part of the development of a humoral response. HLA-class II alleles are considered immune response genes because their codified molecules, expressed on the surface of APCs (macrophages, dendritic, and B cells) present antigenic peptides to T cell via their T cell receptor (TCR). The HLA-class II genes are highly polymorphic, regulating what specific peptides induce follicular helper T cells (TFH) and promote B lymphocyte differentiation into plasma or memory B cells. This work hypothesizes that the presence of certain HLA-class II alleles could be associated with the intensity of the humoral response (amount, length) to the SARS-CoV2 mRNA 1273 vaccine. We have studied the relationship between the HLA-class II typing of 87 health workers and the level of antibodies produced 30 days after vaccination. We show a possible association between the HLA-DRB1* 07:01 allele and the HLA-DRB1*07:01~DQA1*02:01~DQB1*02:02 haplotype to a higher production of antibodies 30 days after the administration of the second dose of mRNA-1273.

Although numerous COVID-19 vaccines are effective against COVID-19 infection and variants of concern (VOC) in the real world, it is imperative to obtain evidence of the corresponding vaccine effectiveness (VE). This study estimates the real-world effectiveness of the BNT162b2 and mRNA-1273 vaccines against COVID-19 infection and determines the influence of different virus variants on VE by using test-negative design (TND) studies. We systematically searched for published articles on the efficacy of BNT162b2 and mRNA-1273 against COVID-19 infection. Two researchers independently selected and extracted data from eligible studies. We calculated the VE associated with different vaccine types, SARS-CoV-2 variants, and vaccination statuses, using an inverse variance random-effects model. We selected 19 eligible studies in the meta-analysis from 1651 records. For the partially vaccinated group, the VE of BNT162b2 and mRNA-1273 was 61% and 78% against COVID-19 infection, respectively. For the completely vaccinated group, the VE of BNT162b2 and mRNA-1273 was 90% and 92% against COVID-19 infection, respectively. During subgroup analyses, the overall VE of BNT162b2 and mRNA-1273 against the Delta variant was 53% and 71%, respectively, for the partially vaccinated group; the respective VE values were 85% and 91% for the fully vaccinated group. Irrespective of the BNT162b2 or mRNA-1273 vaccines, the Delta variant significantly weakened vaccine protection for the partially vaccinated group, while full vaccination was highly effective against COVID-19 infection and various VOC. The mRNA-1273 vaccine is more effective against COVID-19 infection and VOC than the BNT162b2 vaccine, especially for the partially vaccinated group. Overall, the results provide recommendations for national and regional vaccine policies.