SARS-CoV-2 humoral immunity in people living with HIV-1.

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.

Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort study.

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.

Tracking the immune response profiles elicited by the BNT162b2 vaccine in COVID-19 unexperienced and experienced individuals.

Multiple vaccines have been approved to control COVID-19 pandemic, with Pfizer/BioNTech (BNT162b2) being widely used. We conducted a longitudinal analysis of the immune response elicited after three doses of the BNT162b2 vaccine in individuals who have previously experienced SARS-CoV-2 infection and in unexperienced ones. We conducted immunological analyses and single-cell transcriptomics of circulating T and B lymphocytes, combined to CITE-seq or LIBRA-seq, and VDJ-seq. We found that antibody levels against SARS-CoV-2 Spike, NTD and RBD from wild-type, delta and omicron VoCs show comparable dynamics in both vaccination groups, with a peak after the second dose, a decline after six months and a restoration after the booster dose. The antibody neutralization activity was maintained, with lower titers against the omicron variant. Spike-specific memory B cell response was sustained over the vaccination schedule. Clonal analysis revealed that Spike-specific B cells were polyclonal, with a partial clone conservation from natural infection to vaccination. Spike-specific T cell responses were oriented towards effector and effector memory phenotypes, with similar trends in unexperienced and experienced individuals. The CD8 T cell compartment showed a higher clonal expansion and persistence than CD4 T cells. The first two vaccinations doses tended to induce new clones rather than promoting expansion of pre-existing clones. However, we identified a fraction of Spike-specific CD8 T cell clones persisting from natural infection that were boosted by vaccination and clones specifically induced by vaccination. Collectively, our observations revealed a moderate effect of the second dose in enhancing the immune responses elicited after the first vaccination. Differently, we found that a third dose was necessary to restore comparable levels of neutralizing antibodies and Spike-specific T and B cell responses in individuals who experienced a natural SARS-CoV-2 infection.

mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses.

SARS-CoV-2-specific CD8+ T cells recognize conserved viral peptides and in the absence of cross-reactive antibodies form an important line of protection against emerging viral variants as they ameliorate disease severity. SARS-CoV-2 mRNA vaccines induce robust spike-specific antibody and T cell responses in healthy individuals, but their effectiveness in patients with chronic immune-mediated inflammatory disorders (IMIDs) is less well defined. These patients are often treated with systemic immunosuppressants, which may negatively affect vaccine-induced immunity. Indeed, TNF inhibitor (TNFi)-treated inflammatory bowel disease (IBD) patients display reduced ability to maintain SARS-CoV-2 antibody responses post-vaccination, yet the effects on CD8+ T cells remain unclear. Here, we analyzed the impact of IBD and TNFi treatment on mRNA-1273 vaccine-induced CD8+ T cell responses compared to healthy controls in SARS-CoV-2 experienced and inexperienced patients. CD8+ T cells were analyzed for their ability to recognize 32 SARS-CoV-2-specific epitopes, restricted by 10 common HLA class I allotypes using heterotetramer combinatorial coding. This strategy allowed in-depth ex vivo profiling of the vaccine-induced CD8+ T cell responses using phenotypic and activation markers. mRNA vaccination of TNFi-treated and untreated IBD patients induced robust spike-specific CD8+ T cell responses with a predominant central memory and activated phenotype, comparable to those in healthy controls. Prominent non-spike-specific CD8+ T cell responses were observed in SARS-CoV-2 experienced donors prior to vaccination. Non-spike-specific CD8+ T cells persisted and spike-specific CD8+ T cells notably expanded after vaccination in these patient cohorts. Our data demonstrate that regardless of TNFi treatment or prior SARS-CoV-2 infection, IBD patients benefit from vaccination by inducing a robust spike-specific CD8+ T cell response.

Humoral immunity to SARS-CoV-2 in kidney transplant recipients and dialysis patients: IgA and IgG patterns unraveled after SARS-CoV-2 infection and vaccination.

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.

Increased risk of functional neurological disorders following SARS-CoV-2 vaccination.

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.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

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.

Comparison of reporting rates of arthritis and arthralgia following AstraZeneca, Pfizer-BioNTech, Moderna, and Janssen vaccine administration against SARS-CoV-2 in 2021: analysis of European pharmacovigilance large-scale data.

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.

Distinct dynamics of antigen-specific induction and differentiation of different CD11c+Tbet+ B-cell subsets.

BACKGROUND: CD11c+Tbet+ B cells are enriched in autoimmunity and chronic infections and also expand on immune challenge in healthy individuals. CD11c+Tbet+ B cells remain an enigmatic B-cell population because of their intrinsic heterogeneity. OBJECTIVES: We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-specific development and differentiation properties of 3 separate CD11c+ B-cell subsets-age-associated B cells (ABCs), double-negative 2 (DN2) B cells, and activated naive B cells-and compared them to their canonical CD11c- counterparts. METHODS: Dynamics of the response of the 3 CD11c+ B-cell subsets were assessed at SARS-CoV-2 vaccination in healthy donors by spectral flow cytometry. Distinct CD11c+ B-cell subsets were functionally characterized by optimized in vitro cultures. RESULTS: In contrast to a durable expansion of antigen-specific CD11c- memory B cells over time, both ABCs and DN2 cells were strongly expanded shortly after second vaccination and subsequently contracted. Functional characterization of antibody-secreting cell differentiation dynamics revealed that CD11c+Tbet+ B cells were primed for antibody-secreting cell differentiation compared to relevant canonical CD11c- counterparts. CONCLUSION: Overall, CD11c+Tbet+ B cells encompass heterogeneous subpopulations, of which primarily ABCs as well as DN2 B cells respond early to immune challenge and display a pre-antibody-secreting cell phenotype.

Multiple Sclerosis Onset before and after COVID-19 Vaccination: Can HLA Haplotype Be Determinant?

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.

T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells.

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients.

Effects of Second Dose of SARS-CoV-2 Vaccination on Household Transmission, England.

A single SARS-CoV-2 vaccine dose reduces onward transmission from case-patients. We assessed the potential effects of receiving 2 doses on household transmission for case-patients in England and their household contacts. We used stratified Cox regression models to calculate hazard ratios (HRs) for contacts becoming secondary case-patients, comparing contacts of 2-dose vaccinated and unvaccinated index case-patients. We controlled for age, sex, and vaccination status of case-patients and contacts, as well as region, household composition, and relative socioeconomic condition based on household location. During the Alpha-dominant period, HRs were 0.19 (0.13-0.28) for contacts of 2-dose BNT162b2-vaccinated case-patients and 0.54 (0.41-0.69) for contacts of 2-dose Ch4dOx1-vaccinated case-patients; during the Delta-dominant period, HRs were higher, 0.74 (0.72-0.76) for BNT162b2 and 1.06 (1.04-1.08) for Ch4dOx1. Reduction of onward transmission was lower for index case-patients who tested positive ≥2 months after the second dose of either vaccine.

Response to mRNA SARS-CoV-2 vaccination evaluated by B-cell receptor repertoire after tixagevimab/cilgavimab administration.

The use of anti-SARS-CoV-2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID-19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti-spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV-AbDab clearly demonstrated the response to mRNA SARS-CoV-2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.

COVID-19 infection-associated platelet and neutrophil activation is blunted by previous anti-SARS-CoV-2 vaccination.

The effectiveness of vaccination against SARS-CoV-2 in preventing COVID-19 or in reducing severe illness in subjects hospitalized for COVID-19 despite vaccination has been unequivocally shown. However, no studies so far have assessed if subjects who get COVID-19 despite vaccination are protected from SARS-CoV-2-induced platelet, neutrophil and endothelial activation, biomarkers associated with thrombosis and worse outcome. In this pilot study, we show that previous vaccination blunts COVID-19-associated platelet activation, assessed by circulating platelet-derived microvesicles and soluble P-selectin, and neutrophil activation, assessed by circulating neutrophil extracellular trap (NET) biomarkers and matrix metalloproteinase-9, and reduces COVID-19-associated thrombotic events, hospitalization in intensive-care units and death.

SARS-CoV-2 infection and vaccination in patients with hairy-cell leukaemia.

Little is known of the course of COVID-19 and the antibody response to infection or vaccination in patients with hairy-cell leukaemia (HCL). Among a total of 58 HCL cases we studied in these regards, 37 unvaccinated patients, mostly enjoying a relatively long period free from anti-leukaemic treatment, developed COVID-19 between March 2020 and December 2021 with a usually favourable outcome (fatality rate: 5/37, 14%); however, active leukaemia, older age and more comorbidities were associated with a worse course. Postinfection (n = 11 cases) and postvaccination (n = 28) seroconversion consistently developed, except after recent anti-CD20 or venetoclax therapy, correlating with perivaccine B-cell count. Vaccination appeared to protect from severe COVID-19 in 11 patients with breakthrough infection.

T follicular helper cell responses to SARS-CoV-2 vaccination among healthy and immunocompromised adults.

The worldwide rollout of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in the last 2 years has produced a multitude of studies investigating T-cell responses in the peripheral blood and a limited number in secondary lymphoid tissues. As a key component to an effective immune response, vaccine-specific T follicular helper (Tfh) cells are localized in the draining lymph node (LN) and assist in the selection of highly specific B-cell clones for the production of neutralizing antibodies. While these cells have been noted in the blood as circulating Tfh (cTfh) cells, they are not often taken into consideration when examining effective CD4+ T-cell responses, particularly in immunocompromised groups. Furthermore, site-specific analyses in locations such as the LN have recently become an attractive area of investigation. This is mainly a result of improved sampling methods via ultrasound-guided fine-needle biopsy (FNB)/fine-needle aspiration (FNA), which are less invasive than LN excision and able to be performed longitudinally. While these studies have been undertaken in healthy individuals, data from immunocompromised groups are lacking. This review will focus on both Tfh and cTfh responses after SARS-CoV-2 vaccination in healthy and immunocompromised individuals. This area of investigation could identify key characteristics of a successful LN response required for the prevention of infection and viral clearance. This furthermore may highlight responses that could be fine-tuned to improve vaccine efficacy within immunocompromised groups that are at a risk of more severe disease.

Differential effects of selective versus unselective sphingosine 1-phosphate receptor modulators on T- and B-cell response to SARS-CoV-2 vaccination.

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.

BRAF inhibitor treatment of classical hairy cell leukemia allows successful vaccination against SARS-CoV-2.

In classical hairy cell leukemia (HCL), standard treatments including purine analogs achieve a durable response (up to 90%), but lead to severe immunosuppression and long-lasting depletion of CD4 + T lymphocytes. The BRAF inhibitor vemurafenib is effective in HCL, but its use in first-line treatment is restricted to select clinical situations (e.g. active infection). Its impact on immune function or response to vaccines in HCL is unclear. We treated four HCL patients with vemurafenib during the COVID-19 pandemic and monitored immune reconstitution and response to SARS-CoV-2 immunization. All patients responded to HCL treatment with normalization of peripheral blood counts. No severe infections occurred. As an indication of limited immunosuppression by vemurafenib, stable CD4 + and CD8 + T lymphocyte counts and immunoglobulin levels were observed. Three out of four patients received SARS-CoV-2 vaccination (Pfizer-BioNTech) during treatment with vemurafenib. IgG antibody levels against the spike-protein of SARS-CoV-2 were detected (40-818 AE/ml). Our data suggest that vemurafenib has limited effects on cellular and humoral immune function in HCL, which allows for successful SARS-CoV-2 vaccination. These data support the use of BRAF inhibitors during the current pandemic where continued immune response is necessary for minimizing the COVID-19-related risk of non-vaccinated patients.

Third dose of SARS-CoV2 mRNA vaccination produces robust persistent cellular and humoral immune responses in liver transplant recipients.

Weaker responses have been described after two doses of anti-SARS-CoV2 vaccination in liver transplant recipients (LTRs). At the Italian National Institute for Infectious Diseases, 122 LTRs (84% males, median age 64 years) were tested for humoral and cell-mediated immune response after a third doses of anti-SARS-CoV2 mRNA vaccines. Humoral response was measured by quantifying anti-receptor binding domain and neutralizing antibodies; cell-mediated response was measured by quantifying IFN-γ after stimulation of T cells with SARS-CoV-2-specific peptides. Humoral and cellular responses improved significantly compared to the second vaccine dose; 86.4% of previous non-responders to the first 2 vaccine doses (N = 22) became responders. Mycophenolate mofetil-containing regimens were not associated with lower response rates to a third vaccine; shorter time since transplantation (<6 years) was associated with lower humoral and cellular responses to third vaccine. Protective antibodies against Omicron variant were detected in 60% of patients 12 weeks after third vaccine dose.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. METHODS: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. DISCUSSION: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.