Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative ...malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose.
Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher' exact test and the Mann-Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively.
At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed.
BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).
In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after ...the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue. Keywords: mRNA vaccine, COVID-19, Ph negative myeloproliferative neoplasms
A pronounced polarization of healthcare resources and workforce towards the prevention of the rapid spread of SARS-CoV-2 occurred at the expenses of the majority of chronic diseases and cancer, thus ...jeopardizing continuity of care and therapy outcomes. In this challenging and overwhelming scenario, our Institute confirmed its mission to provide expert cancer care. Here, we provide a report of strategic decisions made and of articulated measures developed to limit virus spreading while striving to make our hospital closer to patients.
We hope our experience may serve as a resource to inform clinical care models in case of future epidemiological outbreaks.
Background: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. Methods: An immunogenicity ...evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. Results: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53–339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. Conclusions: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.
Background: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to ...analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). Methods: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. Results: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47–56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). Conclusions: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.
Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients.
To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy.
We measured SARS-CoV-2 anti-spike antibodies, anti-
neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-
). T cell response was assessed at T post-3D.
An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the
variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-
neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the
variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts.
FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.
Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre ...seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension.
An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks’ time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing.
248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5–327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1–46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively).
99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine.
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•The effects of deficit irrigation on maize yield and WUE were evaluated.•Rainfed maize grain production was drastically reduced in the years of low rainfall.•Water productivity of maize production ...increased with deficit irrigation.•Deficit irrigation at 50 and 75% of the full requirement may be a valuable practice.
In Vojvodina region, water deficit during the growing season is a major factor limiting maize production. Therefore, to achieve the ideal soil water content in this region, it is of crucial importance to optimize irrigation. The effects of different irrigation levels with sprinkler irrigation system on crop yield, yield components, water use, water (WUE) and irrigation water use (IWUE) efficiency of maize (Zea mays L.) were investigated in Vojvodina (northern Serbia), on a Calcaric Chernozem soil in temperate environment for 3 consecutive years (2006–2008). Maize was subjected to four irrigation regimes, as follows: non-limited irrigation (I100), 75% of non-limited irrigation (I75), 50% of non-limited irrigation (I50), and rainfed (non-irrigated) as the control (I0). The irrigation treatments were arranged in a complete randomized block design with 4 replicates. Results showed that maize grown in rainfed conditions had high annual variability, mainly due to amount of rainfall and its distribution during the crop-growing seasons. A significant irrigation effect was found for yield, yield components and others investigated parameters under study. Water stress had significant impact on yield response: as an average of the three years, a grain yield increase of 47.8, 32.8, and 22.9% was observed in I100, I75 and I50 treatments compared to rainfed (I0) treatment, respectively. Yield increased linearly with seasonal crop evapotranspiration and irrigation amount. Furthermore, WUE is maximized with a moderate water deficit (I50), while IWUE is the highest in I100 treatment. The deficit irrigation stress index, DISI, decreased with increasing irrigation rate. The results revealed that irrigation is necessary for maize cultivation because rainfall is insufficient to meet the crop water needs in Vojvodina. In addition, the study indicated that the irrigation regime of 25% water saving (I75) could ensure satisfactory grain yield of maize and increment of WUE.
•SF-36 is able to capture specific life domains omitted by standard outcome measures.•SF-36 score at day 14 is an independent predictor of SF-36 score at month 6.•Neurologists should look both on ...disability and quality of life in GBS patients.
Longitudinal health-related quality of life (QoL) data in Guillain-Barré (GBS) patients are still scarce. We, therefore, investigated health- related QoL in GBS patients from Serbia and surrounding countries during a six-month follow-up period, and analyzed its association with patients' disability. Our study comprised 74 adult patients diagnosed with GBS from May 2017 until May 2018 in seven tertiary healthcare centers. Health-related QoL was investigated using the SF-36 questionnaire, and compared with functional disability assessed by the GBS disability scale (GDS). Tests were performed at day 14, day 28, month 3 and month 6 from disease onset. GDS and SF-36 scores improved over time (p < 0.01). GDS scores were different at all four time points, while SF-36 did not differ between day 14 and day 28. Pooled SF-36 scores (especially physical ones) correlated with pooled GDS scores, except for Bodily Pain and Role Emotional scores. We found that GDS score at day 14 was an independent predictor of GDS score at month 6 (β = +0.52, p < 0.01), while SF-36 score at day 14 was an independent predictor of SF-36 score at month 6 (β = +0.51, p < 0.01). Neurologists should look not only on disability but also on QoL in GBS patients, since these two measures provide us with important complementary items of information.
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