ABSTRACT
Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (ID, n=25) diseases. We show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to both virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus. Hence, additional booster doses are recommended to frail patients.
ABSTRACT
Treatment with fingolimod for multiple sclerosis (MS) reduces the efficacy of COVID-19 vaccination. We evaluated by a multivariate linear regression model whether main lymphocyte subsets and demographic feature correlated to the subsequent increase in anti-SARS-CoV2 antibodies following the third dose of COVID-19 vaccination in fingolimod-treated MS patients. We found that number and proportion of peripheral blood CD19+ B lymphocytes before the third dose of vaccination in MS patients treated with fingolimod, predict the subsequent increase of anti-SARS-CoV2 antibodies (respectively p = 0.013; p = 0.015). This work suggests that evaluating the numbers of CD19+ B cells may be important to identify patients at risk of not producing SARS-CoV-2 antibodies, with possible reduced protection from COVID-19.
ABSTRACT
BackgroundPatients with solid or hematological tumors, neurological and immune-inflammatory disorders represent potentially fragile subjects with increased risk to experience severe COVID-19 and inadequate response to SARS-CoV2 vaccination. MethodsWe designed a prospective Italian multicentric study to assess humoral and T-cell response to SARS-CoV2 vaccination in patients (n=378) with solid tumors (ST), hematological malignancies (HM), neurological (ND) and immuno-rheumatological diseases (ID). The immunogenicity of primary vaccination schedule and of the booster dose were analyzed. ResultsOverall, patient seroconversion rate after two doses was 62.1%. A significant lower rate was observed in HM (52.4%) and ID (51.9%) patients compared to ST (95.6%) and ND (70.7%); a lower median level of antibodies was detected in HM and ID versus the others (p<0.0001). A similar rate of patients with a positive SARS-CoV2 T-cell response was observed in all disease groups, with a higher level observed in the ND group. The booster dose improved humoral responses in all disease groups, although with a lower response in HM patients, while the T-cell response increased similarly in all groups. In the multivariable logistic model, the independent predictors for seroconversion were disease subgroups, type of therapies and age. Notably, the ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (p<0.0001), but had no effects on the T-cell responses. ConclusionsImmunosuppressive treatment more than disease type per se is a risk factor for low humoral response after vaccination. The booster dose can improve both humoral and T-cell response. Articles main point- Lower rate of seroconversion was observed in fragile patients as compared to healthy controls - The booster dose improves humoral and T-cell response in all fragile patient groups - Immunosuppressive treatment was associated with the worst humoral response to vaccination, but had no effects on T-cell responses.
ABSTRACT
Background@#and Purpose To identify changes in the choroidal thickness (CT) in multiple sclerosis (MS) patients with and without optic neuritis (ON) using enhanced-depth-imaging optical coherence tomography (EDI-OCT). @*Methods@#This cross-sectional study included 96 eyes with MS and 28 eyes of healthy controls.All participants underwent an ophthalmologic examination and EDI-OCT scanning (Spectralis, Heidelberg Engineering, Germany) to assess the CT and the retinal nerve fiber layer (RNFL) thickness. MS patients were divided into two groups: 1) with and 2) without a history of ON. The CT was evaluated in the fovea and at six horizontal and six vertical points at 500, 1,000, and 1,500 µm from the fovea. Paired t-tests were used to compare the groups, and p-value<0.05 was considered as significant. @*Results@#At all 13 measurements points, the CT was thicker in MS patients than in the healthy controls and was thinner in eyes with ON than in the contralateral eyes, but these differences were not statistically significant. However, the CT was always larger in all points in eyes with a history of ON than in the control eyes. The RNFL was significantly thinner (p<0.05) in both MS and ON eyes than in the control eyes. @*Conclusions@#The CT did not differ between MS and control eyes, but it was significantly larger in patients with a history of ON, in whom the RNFL was thinner. Further studies are necessary to establish the possible role of the choroid in MS.
ABSTRACT
BackgroundPatients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced immune response is based also on cellular immunity and there is emerging evidence that anti-SARS-CoV-2 specific CD4 and CD8 T cell responses can be detected after vaccination also in patients with low antibody levels. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection and to identify correlates of reduced protection in frail vaccinated pwMS on different DMTs. MethodsWe designed a long term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis), a prospective multicenter cohort study enrolling pwMS scheduled for SARS-CoV-2 vaccination with mRNA vaccines and tested for SARS-CoV-2 antibodies before and after the second vaccine dose. These patients were followed with periodic phone calls up to a mean time of 6 months, and all the SARS-CoV-2 breakthrough infections were registered. The impact of DMTs on cumulative incidence of breakthrough Covid-19 cases was presented by Kaplan-Meier curves. A multivariable logistic model was run to assess factors associated to a higher risk of breakthrough infections. Findings1705 pwMS (81.6% BNT162b2 and 18.4% mRNA-1273) had a full vaccination cycle (2 vaccine doses, 21/28 days apart). Of them, 1509 (88.5%) had blood assessment 4 weeks after the second vaccine dose. During follow-up, 23 breakthrough Covid-19 infections (cumulative incidence: 1.5%, SE=0.3%) were detected after a mean of 108 days after the second dose (range, 18-230). Of them, 9 were on ocrelizumab, one on rituximab, 4 on fingolimod, 6 on dimethyl-fumarate, one on teriflunomide, and 2 were untreated. Just two cases (a woman on ocrelizumab and a man on teriflunomide) required hospitalization. The probability to be infected was associated only with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.63, p=0.007); an antibody level of 660 U/mL was calculated as the cutoff for higher risk of infection. InterpretationOur data show that the risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. FundingFISM [2021/Special-Multi/001]; the Italian Ministry of Health grant Progetto Z844A 5x1000. Italian Ministry of Health: Ricerca Corrente to IRCCS Ospedale Policlinico San Martino.
