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Post-Coronavirus Disease 2019 (post-COVID-19) syndrome represents a cluster of persistent symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that can severely affect quality of life. The pathogenic mechanisms and epidemiology in different regions are still under evaluation. To assess the outcomes of post-COVID-19 syndrome, we performed a questionnaire-based, cross-sectional study in previously infected individuals. Out of 549 respondents, (male:female ratio: 0.32), 29.5% had persistent symptoms at 3 months, 23.5% had persistent symptoms at 6 months, and 18.3% had persistent symptoms at 12 months after the initial infection. The most common symptoms included fatigue (8.7%), sleep disturbances (7.1%), and cognitive impairment (6.4%). The risk of developing post-COVID-19 syndrome increased for those with more symptoms in the acute phase (OR 4.24, p < 0.001) and those experiencing reinfections (OR 2.405, p < 0.001), while SARS-CoV-2 vaccination halved the risk (OR = 0.489, p = 0.004). Individuals with post-COVID-19 syndrome had a 5.7-fold higher risk of being diagnosed with a new chronic condition, with 44% reporting cardiovascular disease, and a 6.8-fold higher likelihood of needing medical care or leave. Affected individuals reported significant impairments in mobility, pain/discomfort, and anxiety/depression, with 20.7% needing to adjust their work schedules. Overall, patients with post-COVID-19 syndrome require ongoing monitoring and rehabilitation, and further socio-economic impact studies are needed. [ABSTRACT FROM AUTHOR]

Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+ circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination. [ABSTRACT FROM AUTHOR]

Background: Vaccination against SARS-CoV-2 is widely used and confers protection against morbidity and mortality in COVID-19. Little is known about disease severity and outcomes in fully vaccinated patients during hospitalization for COVID-19. Aim: To determine whether vaccination status and time from vaccination-to-hospitalization impacted disease severity in patients admitted with COVID-19. Methods: A multicenter retrospective cohort study was conducted on hospitalized adults with COVID-19 between January 1 and September 8, 2021, in Rhode Island, USA. Vaccination status and markers of disease severity, including C-reactive protein, D-Dimer values, and supplemental oxygen use during hospitalization, were obtained. Results: Two thousand three hundred forty-four patients were included. For every vaccinated patient, three unvaccinated patients were matched for a total of 424 patients in the analytic sample. Vaccinated patients had lower peak C-reactive protein (beta = −39.10, 95% CI [–79.10, −0. 65]) and supplemental oxygen requirements (beta = −38.14, 95% CI [–61.62, −9.91]) compared to unvaccinated patients. Patients who had a greater discrepancy between date of vaccination and admission had higher C-reactive protein (beta = 0.37, 95% CI [0.02, 0.71]) and supplemental oxygen requirements (beta = 0.44, 95% CI [0.15, 0.75]. Conclusion: Vaccination against SARS-CoV-2 was associated with a protective effect on disease severity during hospitalization for breakthrough COVID-19. Time elapsed since vaccination was associated with indicators of greater disease severity suggestive of waning protection over time. [ABSTRACT FROM AUTHOR]

Objective Autoimmune encephalitis includes a heterogeneous group of rare and complex diseases, usually presenting with severe and disabling symptoms, such as behavioral changes, cognitive deficits, and seizures. Method This report presents the case of a 26-year-old man who was diagnosed with autoimmune encephalitis following SARS-CoV-2 vaccination (<40 days). Symptoms first appeared in February 2022 with a temporal seizure, associated with confusion and memory loss. Psychiatric manifestations such as disorientation and altered thought contents emerged soon after. Results Neuroimaging testing showed signs of hypometabolism in occipital, prefrontal, and temporal regions, whereas an extensive neuropsychological assessment revealed the presence of multiple alterations in memory, executive, and visuoconstructive processes. Conclusions In this case, a combination of neuroimaging testing, psychiatric evaluation, and neuropsychological assessment provided evidence for a diagnosis of autoimmune encephalitis post-vaccination. Early recognition is essential in order to prevent clinical progression; avoid intractable epilepsy, brain atrophy, and cognitive impairment; and improve prognosis. [ABSTRACT FROM AUTHOR]

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic. [ABSTRACT FROM AUTHOR]

Abstract Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+ circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination.

Introduction: Vaccination hesitancy is an important barrier to vaccination among IBD patients. The development of adverse events is the main concern reported. The purpose of this monocentric study was to assess SARS-CoV-2 vaccination safety in IBD patients by evaluating the postvaccination flare risk and incidence of overall adverse events. Methods: Surveys were handed out on three consecutive months to each patient presenting at the Crohn-Colitis Centre, where they documented their vaccination status and any side effects experienced after vaccination. Dates of flares occurring in 2021 were recorded from their electronic medical records. Baseline and IBD characteristics and flare incidence were compared between the vaccinated and unvaccinated patients, and among the vaccinated population before and after their vaccination doses. The characteristics of patients who developed side effects and of those who did not were compared. Results: We enrolled 396 IBD patients, of whom 91% were vaccinated. The proportion of patients who experienced flares was statistically not different between the vaccinated and the unvaccinated population (1.8 vs 2.6 flares per 100 person-months (p=0.28)). Among vaccinated patients, there was no difference across the prevaccination, 1month post any vaccination, and more than 1month after any vaccination periods, and between the Spikevax and Cominarty subgroups. Overall, 46% of patients reported vaccination side effects, mostly mild flu-like symptoms. Conclusion: SARS-CoV-2 vaccination with mRNA vaccines seems safe, with mostly mild side effects. The IBD flare risk is not increased in the month following any vaccination. [ABSTRACT FROM AUTHOR]

Abstract Background Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. Methods Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. Results Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. Conclusion Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.

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]

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19–directed chimeric antigen receptor–modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing. [ABSTRACT FROM AUTHOR]

People living with HIV-1 (PLWH) on antiretroviral treatment (ART) present with delayed infection- and vaccine-induced humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with people without HIV-1 (PWOH). However, they eventually reach titers equivalent to those of PWOH. Differential coordination of SARS-CoV-2 Fc effector functions suggests that antibody responses are qualitatively variable in PLWH, with potential implications for vaccination. Intrahost diversity is more pronounced in ART-naive PLWH, who may contribute to the divergence of SARS-CoV-2 lineages and/or the emergence of variants of concern. Existing data on SARS-CoV-2 humoral immunity and intrahost diversity in PLWH supports the need to increase access to ART. Given the substantial number of people living with HIV-1 (PLWH), especially in sub-Saharan Africa, understanding the effectiveness of COVID-19 vaccines and antibody responses to SARS-CoV-2 infection and vaccination is essential. Additionally, the impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in PLWH remains underexplored. Prolonged SARS-CoV-2 shedding, and enhanced intrahost diversity observed for PLWH, might be one of the driving forces behind SARS-CoV-2 evolution in Africa and should be further considered, with public health implications worldwide. The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa. [ABSTRACT FROM AUTHOR]

Background: Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. Methods: Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. Results: Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. Conclusion: Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity. Key learning points: What was known - In high-risk groups such as kidney transplant patients and dialysis patients, the immune system does not function optimally due to several metabolic processes and lifelong use of immunosuppressants. - Severe infection with SARS-CoV-2 in these high-risk groups is known to be associated with a more serious course of the disease. - Severe disease after SARS-CoV-2 infection was rarely reported but all concerned KTRs who lacked immune responses after vaccination. - Antibody levels decreased four weeks post-vaccination, which emphasizes the importance of booster vaccines. - Kidney transplant recipients with prior COVID-19 exhibited higher anti-Spike IgG levels after a single dose of a SARS-CoV-2 mRNA-based vaccine. This study adds - Humoral immune response to SARS-CoV-2 in kidney transplant recipients was more robust following infection than vaccination. - Next to kidney transplant recipients, patients on dialysis with prior COVID-19 exhibited higher anti-RBD and anti-S1S2 IgG levels as well, so hybrid immunity seems the best possible defence against severe COVID-19 disease in both populations. - Kidney transplant recipients showed the highest IgA titres compared to any other group after double-dose vaccination and infection, along with the lowest IgG titres after vaccination. Potential impact - Our results strengthen the need to administer all the recommended vaccines to patients with end-stage renal disease, and to consider booster vaccination. - Our findings make an important contribution to the COVID-19 research field by analysing both IgG and IgA serology and neutralizing antibody capacity after infection and vaccination, leading to a better understanding of the quality of the humoral immune response and its relationship with clinical data. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on semen parameters. The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank of the Center for Reproductive Medicine, Shandong University (Jinan, China). The volunteers had normal sperm concentration before infection. Each volunteer provided semen samples before and after infection. We selected 90 days after infection as the cutoff point. Semen parameters within 90 days after infection of 109 volunteers (group A) were compared with semen parameters before infection. Moreover, semen parameters on or after 90 days after infection of 36 volunteers (group B) were compared with semen parameters before infection. Furthermore, based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster, volunteers in group A and B were further divided into two subgroups separately. Semen parameters were compared before and after infection in each subgroup. Our results showed that in this cohort population, the semen quality in volunteers with normal sperm concentrations before infection decreased after SARS-CoV-2 infection within 90 days, while the semen quality returned to preinfection levels after 90 days. The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.

Abstract Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara). Anti-SARS-CoV-2-Ig were titrated in the cohort 2-weeks after the 2nddose of vaccine. In the Testing-Group, serum neutralizing antibodies (NAb) were assayed and PBMCs isolated from patients were thawed, counted and stimulated with SARS-CoV-2 IGRA stimulation tube set. All patients had a positive ab-response, except in a case. PMMA-patients had higher levels of anti-SARS-CoV-2 IgG (p = 0.031); VG data confirmed these findings (p

Objectives new-onset relapsing-remitting multiple sclerosis (RRMS) has rarely been communicated as a side effect of SARS-CoV-2 vaccination (SC2V). Here we report a patient with new-onset RRMS shortly after the second BNT162b2 vaccine dose, which was diagnosed only after a relapse after the third vaccine dose. Case report the patient is a 31 year-old male who developed eye problems 48 days after the second dose of BNT162b2. The symptoms were attributed to eye strain and gradually disappeared without treatment. Further workup was negative. Three months after the third BNT162b2 dose, urinary urgency developed. Eleven months after the third BNT162b2 dose, he developed sensory and visual disturbances that were noticeable post-exercise and progressed and worsened with alcohol and heat. MRI showed typical lesions that met the Barkhof/Tintore criteria for RRMS. Cerebrospinal fluid (CSF) studies revealed elevated kappa free light chains and positive oligoclonal bands. Because the revised McDonalds criteria were met, RRMS was diagnosed and ocrelizumab was started. Conclusions this case shows that SARS-CoV-2 vaccination can trigger new-onset RRMS, the clinical presentation of SC2V-induced multiple sclerosis is similar to multiple sclerosis due to other triggers, and the severity of the relapses may increase with the number of boosters given. Although, rare, a neurologist should be aware of the presumably rare event in which SC2V triggers new-onset multiple sclerosis.

AbstractIntroduction Vaccination hesitancy is an important barrier to vaccination among IBD patients. The development of adverse events is the main concern reported. The purpose of this monocentric study was to assess SARS-CoV-2 vaccination safety in IBD patients by evaluating the postvaccination flare risk and incidence of overall adverse events.Methods Surveys were handed out on three consecutive months to each patient presenting at the Crohn-Colitis Centre, where they documented their vaccination status and any side effects experienced after vaccination.Dates of flares occurring in 2021 were recorded from their electronic medical records. Baseline and IBD characteristics and flare incidence were compared between the vaccinated and unvaccinated patients, and among the vaccinated population before and after their vaccination doses. The characteristics of patients who developed side effects and of those who did not were compared.Results We enrolled 396 IBD patients, of whom 91% were vaccinated. The proportion of patients who experienced flares was statistically not different between the vaccinated and the unvaccinated population (1.8 vs 2.6 flares per 100 person-months (p = 0.28)). Among vaccinated patients, there was no difference across the prevaccination, 1 month post any vaccination, and more than 1 month after any vaccination periods, and between the Spikevax and Cominarty subgroups. Overall, 46% of patients reported vaccination side effects, mostly mild flu-like symptoms.Conclusion SARS-CoV-2 vaccination with mRNA vaccines seems safe, with mostly mild side effects. The IBD flare risk is not increased in the month following any vaccination.

Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara). Anti-SARS-CoV-2-Ig were titrated in the cohort 2-weeks after the 2nddose of vaccine. In the Testing-Group, serum neutralizing antibodies (NAb) were assayed and PBMCs isolated from patients were thawed, counted and stimulated with SARS-CoV-2 IGRA stimulation tube set. All patients had a positive ab-response, except in a case. PMMA-patients had higher levels of anti-SARS-CoV-2 IgG (p = 0.031); VG data confirmed these findings (p < 0.05). NAb evaluation: PMMA patients passed the positive cut-off value, while in PS group only only 1/8 patient did not respond. PMMA patients showed higher percentages of anti-SARS-CoV-2 S1/RBD-Ig after a complete vaccine schedule (p = 0.028). Interferon-gamma release: PMMA patients showed significantly higher release of IFNγ (p = 0.014). The full vaccination course provided sufficient protection against SARS-CoV-2 across the entire cohort, regardless of dialyzer type. After vaccination, PMMA patients show a better immune response, both humoral and cellular, at the end of the vaccination course than PS patients. [ABSTRACT FROM AUTHOR]

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs. [ABSTRACT FROM AUTHOR]

A few cases of multiple sclerosis (MS) onset after COVID-19 vaccination have been reported, although the evidence is insufficient to establish causality. The aim of this study is to compare cases of newly diagnosed relapsing–remitting MS before and after the outbreak of the COVID-19 pandemic and the impact of COVID-19 vaccination. Potential environmental and genetic predisposing factors were also investigated, as well as clinical patterns. This is a single-centre retrospective cohort study including all patients who presented with relapsing–remitting MS onset between January 2018 and July 2022. Data on COVID-19 vaccination administration, dose, and type were collected. HLA-DRB1 genotyping was performed in three subgroups. A total of 266 patients received a new diagnosis of relapsing–remitting MS in our centre, 143 before the COVID-19 pandemic (until and including March 2020), and 123 during the COVID-19 era (from April 2020). The mean number of new MS onset cases per year was not different before and during the COVID-19 era and neither were baseline patients' characteristics, type of onset, clinical recovery, or radiological patterns. Fourteen (11.4%) patients who subsequently received a new diagnosis of MS had a history of COVID-19 vaccination within one month before symptoms onset. Patients' characteristics, type of onset, clinical recovery, and radiological patterns did not differ from those of patients with non-vaccine-related new diagnoses of MS. The allele frequencies of HLA-DRB1*15 were 17.6% and 22.2% in patients with non-vaccine-related disease onset before and during the COVID-19 era, respectively, while no case of HLA-DRB1*15 was identified among patients with a new diagnosis of MS post-COVID-19 vaccine. In contrast, HLA-DRB1*08+ or HLA-DRB1*10+ MS patients were present only in this subgroup. Although a causal link between COVID-19 vaccination and relapsing–remitting MS cannot be detected, it is interesting to note and speculate about the peculiarities and heterogeneities underlying disease mechanisms of MS, where the interactions of genetics and the environment could be crucial also for the follow-up and the evaluation of therapeutic options. [ABSTRACT FROM AUTHOR]

Background and Aims The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. Methods A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses. Results A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31–3.33) and 8.89 (2.26–35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41–38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53–1.32) and 1.95 (0.53–4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04–0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases. Conclusions The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low. [ABSTRACT FROM AUTHOR]

Background and purpose: The purpose of this study was to evaluate the possible correlation between SARS‐CoV‐2 vaccines and the onset of neurological syndromes. The aim was to challenge the association between SARS‐CoV‐2 vaccinations and the onset of acute functional neurological disorders (FNDs) compared to other neurological syndromes in hospitalized patients. Methods: In this prospective cohort study, all adult inpatients consecutively admitted to a tertiary neurological centre were included. The prevalence and characteristics of neurological syndromes were compared between unvaccinated and vaccinated cases stratified according to the onset from vaccination. The study involved 843 subjects, namely 411 unvaccinated (UVC) and 432 vaccinated cases; these groups were comparable for demographics and clinical diagnosis distribution. Results: Compared to UVC, subjects hospitalized within the first 30 days from vaccine exhibited higher prevalence of FNDs (12.3% vs. 3.6%; odds ratio 4.2, 95% confidence interval 1.6–11.1) and headache (10.8% vs. 5%; odds ratio 4.1, 95% confidence interval 1.9–8.8) but no other neurological syndromes. The FND cases following vaccinations showed similar premorbid conditions and severity but a higher percentage of sensory symptoms and pain compared to UVC FND cases. Conclusions: SARS‐CoV‐2 vaccination is associated with a significant short‐term increased risk of FND and headache requiring hospitalization in an acute neurological setting. [ABSTRACT FROM AUTHOR]

This study investigates the impact of SARS-CoV-2 infection on placental histopathology in pregnant women, comparing outcomes between vaccinated and non-vaccinated individuals. Despite known adverse pregnancy outcomes linked to SARS-CoV-2 infection, the specific effects on the placenta remain unclear. Although vaccination has demonstrated a substantial reduction in infection severity, its impact on placental health requires more insight. Between March 2021 and July 2022, 387 COVID-19-positive women were admitted for delivery. Of these, 98 with non-severe symptoms were analyzed: 35 vaccinated during pregnancy, and 63 non-vaccinated. Two independent pathologists evaluated all placental specimens. The only differing obstetrical characteristic between groups was the mode of delivery (p 0.047), lacking clinical implications. Over 85% of placentas exhibited microscopic abnormalities, predominantly maternal vascular supply disorders (vaccinated 89.1%; unvaccinated 85.5%). Comparing vaccinated and unvaccinated groups revealed statistically significant differences, notably in increased focal perivillous fibrin deposits (IFPFD) [17.1% vs. 33.3% (p 0.04)] and avascular fibrotic villi (AFV) [0% vs. 11.1% (p 0.04)]. Binomial logistic regression confirmed the vaccine's protective role against IFPFD (aOR 0.36; 95%CI 013–0.99) and AVF (aOR 0.06, 95% CI 0.003–0.98). A sub-analysis in vaccinated women showed a positive correlation between the timing of the first dose and IFPFD presence (p 0.018). The lower incidence of maternal and fetal vascular malperfusion placental features in vaccinated women, coupled with the timing correlation, supports the vaccine's protective effect on placental tissue in COVID-19-infected pregnant patients. Notably, no side effects were reported post-vaccination, emphasizing the vaccine's safety and advocating for its secure administration in pregnant populations. • COVID-19 infection causes vascular pathological placental modifications. • SARS-Cov-2 vaccination shows a positive effect on placental histology. • Timing of the first dose seems to affect the risk of placental malperfusion features. • Vaccination against SARS-CoV-2 is safe and protects mother and fetus at the same time. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To evaluate the incidence of infections and the in-hospital mortality rate in older inpatients vaccinated and unvaccinated against SARS-CoV-2. Findings: SARS-CoV-2 vaccination was associated with a lower likelihood of non-SARS-CoV-2 intra-hospital infections and in-hospital mortality. Cross-reactive immunostimulation may explain these findings. Message: This research showed the importance of guaranteeing appropriate SARS-CoV-2 vaccination coverage in older population, which could limit not only the incidence and severity of COVID-19 but also the onset of other acute infectious diseases and the risk of in-hospital mortality. Purpose: Vaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals. Methods: This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records. Results: The sample's mean age was 87.2 years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had 36% lower odds of intra-hospital infections (OR = 0.64, 95%CI 0.44–0.94) and 39% lower in-hospital death (HR = 0.61, 95%CI 0.39–0.95), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization's endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR = 0.63, 95%CI 0.40–0.99). Conclusions: In older inpatients, SARS-CoV-2 vaccination seems to be associated with a lower likelihood of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases. [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]

Objective: To evaluate the risk of miscarriage following SARS‐CoV‐2 vaccination, while accounting for the competing risk of induced abortion. Design: Population‐based cohort study. Setting: Ontario, Canada. Participants: Women aged 15–50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. Methods: Exposure to first SARS‐CoV‐2 vaccination, handled in a time‐varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. Main outcome measures: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine‐Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio‐demographic factors, comorbidities, and biweekly periods. Results: Included were 246 259 pregnant women, of whom 34% received a first SARS‐CoV‐2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person‐days among remotely vaccinated women and 3.2 per 10 000 person‐days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person‐days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91–1.07) and 1.00 (95% CI 0.93–1.08). Conclusions: SARS‐CoV‐2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data. Linked article: This article is commented on by Victoria Male, pp. 423 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17731. [ABSTRACT FROM AUTHOR]

The immune landscape varies among individuals. It determines the immune response and results in surprisingly diverse symptoms, even in response to similar external stimuli. However, the detailed mechanisms underlying such diverse immune responses have remained mostly elusive. The utilization of recently developed single-cell multimodal analysis platforms has started to answer this question. Emerging studies have elucidated several molecular networks that may explain diversity with respect to age or other factors. An elaborate interplay between inherent physical conditions and environmental conditions has been demonstrated. Furthermore, the importance of modifications by the epigenome resulting in transcriptome variation among individuals is gradually being revealed. Accordingly, epigenomes and transcriptomes are direct indicators of the medical history and dynamic interactions with environmental factors. Coronavirus disease 2019 (COVID-19) has recently become one of the most remarkable examples of the necessity of in-depth analyses of diverse responses with respect to various factors to improve treatment in severe cases and to prevent viral transmission from asymptomatic carriers. In fact, determining why some patients develop serious symptoms is still a pressing issue. Here, we review the current "state of the art" in single-cell analytical technologies and their broad applications to healthy individuals and representative diseases, including COVID-19. [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.

Abstract Introduction The risk of SARS-CoV-2 infection or severe coronavirus disease 2019 (COVID-19) has been shown to increase in patients with multiple sclerosis (MS). Vaccination is recommended in this patient population, and the effect of disease-modifying treatments (DMTs) on response to vaccination should be considered. Methods This prospective, observational, cross-sectional study investigated humoral response after COVID-19 vaccination as well as possible predictors for response in patients with MS and other neuroinflammatory diseases who received DMTs in routine clinical practice in Spain. Responses were compared versus those seen in healthy controls. Results After vaccination against COVID-19, most patients with MS developed an immune response comparable to that of healthy individuals. However, approximately half of patients receiving a sphingosine-1-phosphate modulator (SP1-M, fingolimod or siponimod) or a B-cell-depleting agent (aCD20, ocrelizumab or rituximab) did not develop protective antibodies, although patients receiving other DMTs had humoral immune responses comparable to healthy controls. Lymphocyte count was not associated with reduced humoral response in patients receiving an SP1-M or aCD20, whereas, in patients receiving an aCD20 or SP1-M, older age was associated with lower anti-SARS-CoV-2 spike protein immunoglobulin G antibody levels. Conclusions Treatment with aCD20 or SP1-M therapies appears to be associated with a lower humoral response to vaccines against SARS-CoV-2. Vaccination prior to initiation of these DMTs should be recommended whenever possible.

Post-Coronavirus Disease 2019 (post-COVID-19) syndrome represents a cluster of persistent symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that can severely affect quality of life. The pathogenic mechanisms and epidemiology in different regions are still under evaluation. To assess the outcomes of post-COVID-19 syndrome, we performed a questionnaire-based, cross-sectional study in previously infected individuals. Out of 549 respondents, (male:female ratio: 0.32), 29.5% had persistent symptoms at 3 months, 23.5% had persistent symptoms at 6 months, and 18.3% had persistent symptoms at 12 months after the initial infection. The most common symptoms included fatigue (8.7%), sleep disturbances (7.1%), and cognitive impairment (6.4%). The risk of developing post-COVID-19 syndrome increased for those with more symptoms in the acute phase (OR 4.24, p < 0.001) and those experiencing reinfections (OR 2.405, p < 0.001), while SARS-CoV-2 vaccination halved the risk (OR = 0.489, p = 0.004). Individuals with post-COVID-19 syndrome had a 5.7-fold higher risk of being diagnosed with a new chronic condition, with 44% reporting cardiovascular disease, and a 6.8-fold higher likelihood of needing medical care or leave. Affected individuals reported significant impairments in mobility, pain/discomfort, and anxiety/depression, with 20.7% needing to adjust their work schedules. Overall, patients with post-COVID-19 syndrome require ongoing monitoring and rehabilitation, and further socio-economic impact studies are needed.

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient’s demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time.

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves' disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination. SAT, characterized by transient inflammation of the thyroid gland, has been reported after SARS-CoV-2 vaccination. GD, an autoimmune hyperthyroidism, has also been observed post-vaccination, often with stimulating TSH-R-Ab. Graves' orbitopathy (GO) has been associated with SARS-CoV-2 vaccination in patients with a history of immune thyroid disease. The unique case underscores a very rare thyroid condition of functional hypothyroidism in possible relation to SARS-CoV-2 vaccination and the usefulness of functional analysis of TSH-R-Ab that can provide valuable insights into disease pathogenesis and help to guide treatment. This review highlights the need for continued monitoring and awareness of potential thyroid-related complications following SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the reporting rates of arthritis and arthralgia following the administration of four vaccines against SARS-CoV-2: Pfizer-BioNTech (Tozinameran), Moderna (CX-024414), AstraZeneca (Chadox1 NCOV-19), and Janssen (AD26.COV2.S) in 2021. We used data from the EudraVigilance database, specifically analyzing spontaneous reports of suspected adverse reactions (ADRs) from the European Union (EU)/European Economic Area (EEA) region. Age-group-specific reporting rates were calculated by dividing the number of arthralgia and arthritis reports per 1,000,000 vaccine doses administered per age group. Reporting rates were compared using a rate ratio among the four vaccines, using the AstraZeneca vaccine as a comparator. The AstraZeneca vaccine was associated with the highest rate of arthralgia across all age groups. Arthritis reporting rates were significantly lower, with the AstraZeneca vaccine having the highest rates in most age groups, except the 60–69 and 80+ groups, where the Janssen and Pfizer-BioNTech vaccines demonstrated higher reporting rates, respectively. The distribution of arthritis rates did not follow the arthralgia pattern, being higher in the 50–79 age group. This study is the first spontaneous reporting system analysis of arthritis reporting rates post-SARS-CoV-2 vaccination at a European level, revealing a higher reporting of suspected musculoskeletal adverse reactions after AstraZeneca vaccination. The findings underscore the need to consider commonly reported events like arthralgia in risk–benefit assessments prior to vaccination against SARS-CoV-2. Given the high prevalence of rheumatic and musculoskeletal diseases and vaccine hesitancy in this population, our results could influence vaccine choice and acceptance. [ABSTRACT FROM AUTHOR]

Introduction: The risk of SARS-CoV-2 infection or severe coronavirus disease 2019 (COVID-19) has been shown to increase in patients with multiple sclerosis (MS). Vaccination is recommended in this patient population, and the effect of disease-modifying treatments (DMTs) on response to vaccination should be considered. Methods: This prospective, observational, cross-sectional study investigated humoral response after COVID-19 vaccination as well as possible predictors for response in patients with MS and other neuroinflammatory diseases who received DMTs in routine clinical practice in Spain. Responses were compared versus those seen in healthy controls. Results: After vaccination against COVID-19, most patients with MS developed an immune response comparable to that of healthy individuals. However, approximately half of patients receiving a sphingosine-1-phosphate modulator (SP1-M, fingolimod or siponimod) or a B-cell-depleting agent (aCD20, ocrelizumab or rituximab) did not develop protective antibodies, although patients receiving other DMTs had humoral immune responses comparable to healthy controls. Lymphocyte count was not associated with reduced humoral response in patients receiving an SP1-M or aCD20, whereas, in patients receiving an aCD20 or SP1-M, older age was associated with lower anti-SARS-CoV-2 spike protein immunoglobulin G antibody levels. Conclusions: Treatment with aCD20 or SP1-M therapies appears to be associated with a lower humoral response to vaccines against SARS-CoV-2. Vaccination prior to initiation of these DMTs should be recommended whenever possible. [ABSTRACT FROM AUTHOR]

Background: The aim of the rapid introduction of vaccines during the COVID-19 pandemic was a reduction in SARS-CoV-2 transmission and a less frequent occurrence of severe COVID-19 courses. Thus, we evaluated COVID-19 severity in vaccinated individuals to examine variant-specific symptom characteristics and their clinical impact on the serological immune response. Methods: A total of 185 individuals previously vaccinated against and infected with the SARS-CoV-2 Delta (B.1.617.2) or Omicron (BA.4 and BA.5) variant, were enrolled for anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig level detection. A structured survey regarding medical history was conducted. Results: In 99.5 percent of cases, outpatient treatment was satisfactory. Specific symptoms associated with variants included ageusia and anosmia in patients with Delta infections and throat pain in Omicron infections. Among Delta-infected individuals with specific symptoms, significantly higher levels of anti-N antibodies were observed. Conclusion: Our study identified variant-specific differences in the amount of SARS-CoV-2 antibody production and COVID-19 symptoms. Despite this, vaccinated individuals with Omicron or Delta infections generally experienced mild disease courses. Additionally, asymptomatic individuals exhibit lower anti-SARS-CoV-2 antibody levels, indicating a clinical correlation between disease-specific antibodies and distinct symptoms, particularly in the case of the Delta variant. In follow-up studies, exploring post-COVID syndrome and focusing on cognitive symptoms in the acute phase of Omicron infections is crucial as it has the potential to longitudinally impact the lives of those affected. [ABSTRACT FROM AUTHOR]

The evidence of SARS-CoV-2 vaccine effectiveness in people living with HIV (PLWH) is limited. This study evaluated the humoral immune response to CoronaVac™ (virus inactivated) and BNT162b2 (mRNA- based) vaccines in PLWH and HIV-negative controls, with and without a booster sequence. We conducted a cross-sectional study on PLWH and HIV-negative controls who received CoronaVac or BNT162b2, with a subgroup receiving a CoronaVac/BNT162b2 booster. Blood samples were collected 4–6 months after primary vaccination and tested for anti-SARS-CoV-2 protein S (aSAb) and neutralizing antibodies (NtAb) using validated assays. Immune response was evaluated by age, sex, previous COVID-19 history, and CD4 + cell count. One hundred and eighty nine participants were enrolled with 161 (85%) being PLWH. Among participants without previous known COVID-19, median aSAb levels were significantly lower in PLWH who received CoronaVac compared to BNT162b2 (32 U/mL vs. 587 U/mL, p < 0.001), with similar results in HIV-negative controls. NtAb presence was also significantly lower after CoronaVac compared to BNT162b2 (30% vs. 93%, p < 0.001). The booster sequence group showed a significant increase in aSAb titers in both PLWH and HIV-negative controls (from 33 U/ml to 2500 U/ml, p < 0.001), and NtAb positivity increased from 20% to 95 % in PLWH, and 27% to 100% in HIV-negative controls. Prior COVID-19 led to significantly higher post-vaccine antibody titers particularly in the BNT162b2 group. PLWH with CD4 + count < 200 cells/mL showed a weaker immune response to both vaccines. CoronaVac resulted in a weaker immune response in both PLWH and HIV-negative controls compared to BNT162b2, particularly in immunosuppressed PLWH without prior COVID-19. Hybrid immunity and heterologous booster vaccination increased antibody levels. Local funding. [ABSTRACT FROM AUTHOR]

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]

SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population. [ABSTRACT FROM AUTHOR]

Introduction and Objective. In recent years, cases of secondary glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) have been reported following COVID-19 infection or vaccination against SARS-CoV-2. The aim of the study was to analyze publications related to this issue and to highlight both the benefits of vaccination and the potential for secondary immune responses to both infection and vaccination against COVID-19./ Review Methods. A literature review was conducted on sources available up to December 2023, utilizing databases such as PubMed, Cochrane, and Google Scholar. The analysis included cases of ANCA-associated glomerulonephritis (ANCA-GN) following SARS-CoV-2 infection and after COVID-19 vaccination. Brief description of the state of knowledge. ANCA-associated vasculitis (AAV) is an inflammation of small and medium vessels affecting all systems, including the kidneys. Various causes contribute to the development of AAV, including pathogenic microorganisms and individual abnormal reactions to vaccinations, which can lead to autoimmunization. Since the Covid-19 pandemic, cases of ANCA-GN have been observed in patients without prior autoimmune diseases. The rapid progression of the COVID-19 pandemic led to a significant acceleration in the development of dedicated vaccines, thereby preventing a considerable number of deaths caused by the infection. Summary. ANCA-associated glomerulonephritis post COVID-19 can be linked to both infection and vaccination, which may act as triggers for autoimmune responses. These mechanisms require further investigation. Vaccine-induced ANCA-GN following COVID-19 vaccination is rare, and vaccinations represent an appropriate strategy to combat this disease. [ABSTRACT FROM AUTHOR]

Background: Sphingosine 1-phosphat receptor modulators (S1PRMs) have been linked to attenuated immune response to SARS-CoV-2 vaccines. Objective: To characterize differences in the immune response to SARS-CoV-2 vaccines in patients on selective versus unselective S1PRMs. Methods: Monocentric, longitudinal study on people with multiple sclerosis (pwMS) on fingolimod (FTY), siponimod (SIP), ozanimod (OZA), or without disease-modifying therapy (DMT) following primary and booster SARS-CoV-2 vaccination. Anti-SARS-CoV-2 antibodies and T-cell response was measured with electro-chemiluminescent immunoassay and interferon-γ release assay. Results: Primary vaccination induced a significant antibody response in pwMS without DMT while S1PRM patients exhibited reduced antibody titers. The lowest antibodies were found in patients on FTY, whereas patients on OZA and SIP presented significantly higher levels. Booster vaccinations induced increased antibody levels in untreated patients and comparable titers in patients on OZA and SIP, but no increase in FTY-treated patients. While untreated pwMS developed a T-cell response, patients on S1PRMs presented a diminished/absent response. Patients undergoing SARS-CoV-2 vaccination before onset of S1PRMs presented a preserved, although attenuated humoral response, while T-cellular response was blunted. Conclusion: Our data confirm differential effects of selective versus unselective S1PRMs on T- and B-cell response to SARS-CoV-2 vaccination and suggest association with S1PRM selectivity rather than lymphocyte redistribution. [ABSTRACT FROM AUTHOR]

Background: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. Methods: We studied 50 kidney transplant recipients following SARS‐CoV‐2 vaccination and quantified their anti‐spike protein antibody, donor‐derived cell‐free DNA (dd‐cfDNA), gene expression profiling (GEP), and alloantibody formation. Results: Participants were stratified using nucleocapsid testing as either SARS‐CoV‐2‐naïve or experienced prior to vaccination. One of 34 (3%) SARS‐CoV‐2 naïve participants developed anti‐spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS‐CoV‐2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre‐ and post‐vaccination levels did not change for median dd‐cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de‐novo donor specific antibody status, or estimated glomerular filtration rate. Conclusions: SARS‐CoV‐2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Background: As the world's population of people vaccinated with the COVID‐19 vaccine increases, adverse reactions are increasingly being reported. There have been progressive reports of the effects of COVID‐19 vaccination on cosmetic fillers or prostheses, but they have not been reviewed based on their clinical morphologic patterns. This article reviewed the progress of research on adverse reactions to cosmetic implants after COVID‐19 vaccination. Methods: We researched the English‐language literature up to October 15, 2022, using predefined keywords to identify relevant studies about adverse reactions to cosmetic implants after the COVID‐19 vaccination, collecting patient characteristics, implant type, the time interval between vaccination and implantation or injection, time of onset, symptoms, treatments, and outcomes. Results: Among the adverse reactions to implants associated with COVID‐19 vaccination, we distinguished between (1) injectable fillers and (2) surgical prosthetic implants. The most common adverse reactions were at the site of hyaluronic acid injection and breast prosthesis after Pfizer vaccination, mainly DIRs, and mainly manifested as edema, rash, fever, and capsular contracture. This paper also reported the possible causes, treatments of DIRs, and limitations of current studies. Conclusions: In this article, we attempted to investigate and discuss all the adverse reactions of cosmetic implants related to COVID‐19 vaccination in the current literature, to unmask these reactions and make a more accurate assessment of vaccine safety. [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.

Neuromuscular manifestations of SARS-CoV-2 vaccinations have been reported increasingly over the last years. Specifically, cranial multineuropathies are extremely rare entities and few cases have been reported related to COVID-19, whereas, todate, no case has been observed after vaccine against SARS-CoV-2. Herein we describe a patient who presented ptosis, ophthalmoparesis and a subclinical facial nerve impairment after two weeks from the second dose of AZD1222 (ChAdOx1-S [recombinant]) vaccine.

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.