Humoral Immune Response to Sars-Cov-2 Third Vaccine in Patients with Autoimmune Rheumatic Diseases without Seroconversion after the Initial 2-Dose Regimen

Objectives: To evaluate the humoral immune response to the third dose (booster) of vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases who were seronegative after a two-dose regimen. Method(s): Observational study. Patients with autoimmune rheumatic diseases who had not achieved seroconversion after a two-dose vaccine schedule against SARS-CoV-2 were included. To assess the humoral immune response, anti-RBD IgG (S protein receptor binding domain) neutralizing antibody titers were determined by ELISA (cutoff titer 200). The determination was made between 30 to 45 days after the third dose. Result(s): From 66 patients who received SARS-CoV-2 vaccination, 18 patients (29.5%) were seronegative after a two-dose schedule. 61% had SLE, 77% had comorbidities (61% with hypertension, p = 0.03). Patients were on treatment: 10 with prednisone (8 with doses greater than 10 mg/d, p = 0.01), 10 with hydroxychloroquine, one with methotrexate, one with leflunomide, four with azathioprine, five with my cophenolatemofetil and five with rituximab (they are the total number of non-responders on biological treatment, p = 0.03). Regarding the primary vaccination regimen, 11 received BBIBP-CorV (p = 0.01), 5 AZD1222, 1 Gam-COVID-Vac and 1 mRNA1273/Gam-COVID-Vac heterologous scheme. Of these 18 non-responders, 14 received a third dose;nine patients (62%) presented anti-RBD IgG detectable. Of the five patients who did not respond to the booster vaccination, three had received BBIBP-CorV as the initial schedule and the vaccines applied as a third dose were Ad5-nCoV (1), BNT162b2 (1), AZD 1222 (2) and Gam-COVID-Vac (1). They were being treated with: rituximab (2), azathioprine (2) and mycophenolate mofetil (1). Treatment with higher doses of prednisone was the only factor associated with non-seroconversion to the third dose (8 +/- 4.5;p 0.02). Conclusion(s): The third dose of SARS-CoV-2 vaccine allowed to improve the serological response to vaccination, achieving a seroconversion of 62% in this group of patients.

IMMUNE RESPONSES TO MRNA AND INACTIVATED COVID-19 VACCINES AMONG HEALTHCARE WORKERS IN HONG KONG

COVID-19 vaccines against the earlier strains of SARS-CoV-2 are now available. However, breakthrough infections can still occur due to waning antibodies and immune escape by new variants. We assessed humoral immune responses to the mRNA (BNT162b2) and inactivated (CoronaVac) vaccines in our healthcare worker cohort (HCW). We recruited HCWs from public and private healthcare institutions across Hong Kong and collected blood samples at enrolment and every 6 months from June 2020 to June 2022. A subset of volunteers provided blood samples between 10 – 42 days after each dose of vaccine. Immune responses to vaccination were measured as SARS-CoV-2 binding antibodies detected by an enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 neutralising antibodies by surrogate virus neutralization test (sVNT) and plaque reduction neutralization test (PRNT). Among the 1,736 HCWs enrolled in our cohort, 252 HCWs provided pre- and post-vaccination blood samples after each dose of either vaccine. Two doses of BNT162b2 generated levels of neutralizing antibodies (sVNT inhibition = 96.8%, range = 42.8%, 98.2%) comparable to those generated by natural infections in the first wave (sVNT inhibition = 84.0%, range = 32.9%, 93.8%). Similar levels were achieved with three doses of CoronaVac (sVNT inhibition = 95.3%, range = 64.7%, 98.3%) and heterologous vaccination with two doses of CoronaVac followed by a booster dose of BNT162b2 vaccine (sVNT inhibition = 97.0%, range = 85.8%, 97.7%). These antibody levels waned faster after second doses and slower after third doses for both vaccines. The BNT162b2 vaccine and CoronaVac vaccines can generate robust antibody responses comparable to natural infections. Three doses of the CoronaVac vaccine, or a heterologous boost with the BNT162b2 vaccine following two doses of the CoronaVac vaccine are required to achieve similar levels of neutralising antibodies in vaccinees who received two doses of the BNT162b2 vaccine. [ FROM AUTHOR] Copyright of International Journal of Infectious Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Efficacy and safety of a fourth dose of the COVID-19 vaccine in kidney transplant recipients: A systematic review and meta-analysis

Background Kidney transplant recipients (KTRs) who become infected with SARS-CoV-2 are at greater risk of serious illness and death than the general population. To date, the efficacy and safety of the fourth dose of the COVID-19 vaccine in KTRs have not been systematically discussed. Methods This systematic review and meta-analysis included articles from PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang Med Online published before May 15, 2022. Studies evaluating the efficacy and safety of a fourth dose of the COVID-19 vaccine in kidney transplant recipients were selected. Results Nine studies were included in the meta-analysis, with a total of 727 KTRs. The overall pooled seropositivity rate after the fourth COVID-19 vaccine was 60% (95% CI, 49%–71%, I2 = 87.83%, p > 0.01). The pooled proportion of KTRs seronegative after the third dose that transitioned to seropositivity after the fourth dose was 30% (95% CI, 15%–48%, I2 = 94.98%, p < 0.01). Conclusions The fourth dose of the COVID-19 vaccine was well tolerated in KTRs with no serious adverse effects. Some KTRs showed a reduced response even after receiving the fourth vaccine dose. Overall, the fourth vaccine dose effectively improved seropositivity in KTRs, as recommended by the World Health Organization for the general population.

The impact of CoronaVac on the neutralization breadth and magnitude of the antibody response to SARS-CoV-2 viruses.

Although immune response enhancement has been reported after primary and booster vaccines of CoronaVac, neutralization breadth of SARS-CoV-2 variants is still unclear. In the present study, we examined the neutralization magnitude and breadth of SARS-CoV-2 variants including Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) in 33 convalescent COVID-19 patients and a cohort of 55 medical staff receiving primary CoronaVac vaccines and an additional homologous booster dose. Results showed that, as compared with the two-dose primary vaccination, the homologous booster dose achieved 2.24-, 3.98-, 4.58- and 2.90-fold increase in neutralization titer against wild-type, Beta, Delta, and Omicron, respectively. After booster dose, neutralization titer reduction for variants was less than that after the primary vaccine or that for convalescents. The proportion of recipients able to neutralize 2 or more variants increased from 36.36% post the primary vaccination to 87.27% after the booster. Significant increase in neutralization breadth of 1.24 (95% confidence interval (CI), 0.89-1.59) variants was associated with a log10 increase in neutralization titer against the wild-type. In addition, anti-RBD IgG level was identified as an excellent surrogate for positive neutralization of SARS-CoV-2 and neutralization breadth of variants. These findings highlight the value of an additional homologous CoronaVac dose in broadening the cross-neutralization against SARS-CoV-2 variants, and are critical for informing the booster dose vaccination efforts.

Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2.

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3rd (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination. Moreover, vaccination induced activated T cells expressing CD69, CD137 and producing IFN-γ and TNF-α. Virus-specific CD8 T cells showed predominantly memory phenotype. Although the level of antibodies and frequency of virus-specific T cells reduced 4-6 months after the 2nd dose, they were augmented after the 3rd dose followed by a decrease later. Importantly, T cells generated after the 3rd vaccination were also reactive against Omicron variant, indicated by a similar level of IFN-γ production after stimulation with Omicron peptides. Breakthrough infection in participants vaccinated with two doses induced more SARS-CoV-2-specific T cells than the booster vaccination. We found an upregulation of PD-L1 expression on monocytes but no accumulation of myeloid cells with MDSC-like immunosuppressive phenotype after the vaccination. Our results indicate that the 3rd vaccination fosters antibody and T cell immune response independently from vaccine type used for the first two injections. However, such immune response is attenuated over time, suggesting thereby the need for further vaccinations.

Waning of specific antibodies against Delta and Omicron variants five months after a third dose of BNT162b2 SARS-CoV-2 vaccine in elderly individuals.

The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron variants, has raised concerns on efficacy of the COVID-19 vaccines. Here, we examined the waning of antibody responses against different variants following primary and booster vaccination. We found that antibody responses against variants were low following primary vaccination. The antibody response against Omicron was almost non-existent. Efficient boosting of antibody response against all variants, including Omicron, was observed following a third dose. The antibody response against the variants tested was significantly higher at one month following booster vaccination, compared with two months following primary vaccination, for all individuals, including the low antibody responders identified at two months following primary vaccination. The antibody response, for all variants tested, was significantly higher at four months post booster than at five months post primary vaccination, and the proportion of low responders remained low (6-11%). However, there was significant waning of antibody response in more than 95% of individuals at four months, compared to one month following booster. We also observed a robust memory B cell response following booster, which remained higher at four months post booster than prior to booster. However, the memory B cell responses were on the decline for 50% of individuals at four months following booster. Similarly, while the T cell response is sustained, at cohort level, at four months post booster, a substantial proportion of individuals (18.8 - 53.8%) exhibited T cell response at four months post booster that has waned to levels below their corresponding levels before booster. The findings show an efficient induction of immune response against SARS-CoV-2 variants following booster vaccination. However, the induced immunity by the third BNT162b2 vaccine dose was transient. The findings suggest that elderly individuals may require a fourth dose to provide protection against SARS-CoV-2.

Comparison of the reactogenicity and immunogenicity between two-dose mRNA COVID-19 vaccine and inactivated COVID-19 vaccine followed by an mRNA vaccine in children aged 5-11 years.

To compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5 and 11 years of age, a prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5 and 11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1 and 3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding antibodies to wild-type SARS-CoV-2. Neutralizing antibodies to Omicron variants (BA.2 and BA.5) were tested using the focus reduction neutralization test. Overall, 166 eligible children were enrolled. Local and systemic adverse events which occurred within 7 days after vaccination were mild to moderate and well-tolerated. The two-dose BNT162b2, CoronaVac followed by BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 groups elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against the Omicron BA.2 and BA.5 variant than the CoronaVac followed by BNT162b2 group. The CoronaVac followed by BNT162b2 group elicited low neutralizing activities against the Omicron BA.2 and BA.5 variant. A third dose (booster) mRNA vaccine should be prioritized for this group.

Changes in SARS-CoV-2 antibody titers 6 months after the booster dose of BNT162b2 COVID-19 vaccine among health care workers.

Purpose: In Japan, the data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers after the booster dose of the coronavirus disease 2019 (COVID-19) vaccine are insufficient. The aim of this study is to evaluate changes in SARS-CoV-2 antibody titers before, 1, 3, and 6 months after the booster dose of the BNT162b2 COVID-19 vaccine among health care workers. Materials and Methods: A total of 268 participants who received the booster dose of the BNT162b2 vaccine were analyzed. SARS-CoV-2 antibody titers were measured before (baseline) and at 1, 3, and 6 months after the booster dose. Factors associated with changes in SARS-CoV-2 antibody titers at 1, 3, and 6 months were analyzed. Cutoff values at baseline were calculated to prevent infection of the omicron variant of COVID-19. Results: The SARS-CoV-2 antibody titers at baseline, and 1, 3, and 6 months were 1,018.3 AU/mL, 21,396.5 AU/mL, 13,704.6 AU/mL, and 8,155.6 AU/mL, respectively. Factors associated with changes in SARS-CoV-2 antibody titers at 1 month were age and SARS-CoV-2 antibody titers at baseline, whereas changes in SARS-CoV-2 antibody titers at 3 and 6 months were associated with the SARS-CoV-2 antibody titers at 1 month. The cutoff values of the SARS-CoV-2 antibody titers at baseline were 515.4 AU/mL and 13,602.7 AU/mL at baseline and 1 month after the booster dose, respectively. Conclusion: This study showed that SARS-CoV-2 antibody titers increase rapidly at 1 month after the booster dose of the BNT162b2 vaccine and begin to decrease from 1 to 6 months. Hence, another booster may be needed as soon as possible to prevent infection.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Risk factors and characteristics influencing humoral response to COVID-19 vaccination in patients after allogeneic stem cell transplantation.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARS-CoV-2 vaccination in a bicentric population of allogeneic transplanted patients. Methods: We retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination. Results: A total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts <200/µl, p< 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion. Discussion: We showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose.

Cellular and humoral response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL.

We assessed the humoral and cellular response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL. A total of 67 patients with CLL and 85 age matched controls tested for serologic response and pseudo-neutralization assay. We also tested the functional T-cell response by interferon gamma (IFNγ) to spike protein in 26 patients. Two weeks after the fourth vaccine antibody serologic response was evident in 37 (55.2%) patients with CLL, 20 /22 (91%) of treatment naïve, and 9/32 (28%) patients with ongoing therapy, compared with 100% serologic response in age matched controls. The antibody titer increased by 10-fold in patients with CLL, however, still 88-folds lower than age matched controls. Predictors of better chances of post fourth vaccination serologic response were previous positive serologies after second, third, and pre-fourth vaccination, neutralizing assay, and treatment naïve patients. T-cell response improved from 42.3% before the fourth vaccine to 84.6% 2 weeks afterwards. During the time period of 3 months after the fourth vaccination, 14 patients (21%) developed COVID-19 infection, all recovered uneventfully. Our data demonstrate that fourth SARS-CoV-2 vaccination improves serologic response in patients with CLL to a lesser extent than healthy controls and induces functional T-cell response.

Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs.

BACKGROUND: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. OBJECTIVES: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). METHODS: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. RESULTS: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. CONCLUSION: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease.

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai Older adults.

INTRODUCTION: Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. METHODS: Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12-24 weeks earlier were randomized to receive a booster vaccination by either ID (20-mcg mRNA1273 or 10-mcg BNT162b2) or intramuscular (IM) (100-mcg mRNA1273 or 30-mcg BNT162b2) route. Anti-receptor binding domain (anti-RBD) IgG, neutralizing antibody (NAb), and IFNγ-producing cells were measured at 2-4 weeks following vaccination. RESULTS: Of 210 participants enrolled, 70.5% were female and median age was 77.5 years (interquartile range: 71-84). Following booster dose, both ID vaccination induced 37% lower levels of anti-RBD IgG than IM vaccination of the same vaccine. NAb titers against ancestral and omicron BA.1 was highest following IM mRNA-1273 (geometric mean 1,718 and 617), followed by ID mRNA-1273 (1,212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFNγ responses were similar or higher in the ID groups when compared with IM groups. ID route tended to have lower systemic AEs, although more local AEs reported in ID mRNA-1273 group. CONCLUSIONS: Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative option for older people.

A febrile reaction is associated with high IgG antibody titers after the second and third BNT162b2 vaccination in Japan.

Adverse events are potentially associated with an IgG response after the BNT162b2 vaccination for severe acute respiratory syndrome coronavirus 2. In this study, we investigated the side effects of BNT162b2 vaccination using a health questionnaire and examined its relationship with IgG antibody titers. Serum samples were collected from participants 3 months after the second vaccination, just before the third vaccination, and 1 and 3 months after the third vaccination. A total of 505 participants who received three doses of vaccination were eligible for analysis. The results showed that post-vaccination body temperature correlated with anti-spike-receptor-binding domain (anti-S-RBD) antibody titers analyzed 3 months after the second (r = 0.30, p < 0.001) and third (r = 0.14, p < 0.001) vaccinations. Multivariate linear regression analysis revealed that age and severe swelling were negatively associated with log-transformed anti-S-RBD antibody levels, whereas sex (female), body temperature, and heat sensation were positively associated after the second vaccination. After the third vaccination, body temperature, and fatigue were positively associated with log-transformed anti-S-RBD antibody levels, and sex (female) was negatively associated. These results indicate that post-vaccination fever may be a marker of increased antibody titer.

Breakthrough infections and acceptance of COVID-19 vaccine boosters: A survey analysis.

Objective: This Short Communication explores the effect of COVID-19 breakthrough infections (defined as a COVID-19 diagnosis after vaccination) on the willingness of previously vaccinated individuals to receive ongoing vaccine boosters. Specifically, we examine unique effects for three different breakthrough infection experiences, including the participant themselves, a close member of their family, and a friend/coworker. Methods: A representative, web-based survey of 600 adults in the state of Florida was fielded in March/April of 2022. Among the respondents, 455 had been vaccinated against COVID-19. Their responses were analyzed for this study using both descriptive and inferential statistical methods. Results: Individuals who have experienced a personal breakthrough infection are two times less likely to receive annual vaccine boosters, ceteris paribus. However, there is not a statistically significant relationship between vaccine acceptance and breakthrough infections among close family members or friends/coworkers. We also found a very strong relationship between vaccine decisions and confidence in public health guidance. Conclusion: Our findings show that confidence in public health guidelines is the most compelling determinant of vaccine acceptance, but breakthrough infections also have a significant impact on individual decision making when it comes to ongoing vaccination. Going forward, public health messaging should directly account for this correlation in order to effectively maintain vaccination levels. Innovation: The COVID-19 pandemic marked a turning point in the development and deployment of mRNA vaccines. This study contributes to innovation in health communication research by examining how breakthrough infections in these vaccinated individuals impacts ongoing booster shot acceptance. The findings of this study contribute to the nascent and ongoing development of baseline research in this area.

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: who gains from it?

BACKGROUND: Although two doses of Covid-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease modifying therapies (DMTs) showed less efficient responses. METHODS: This prospective multiCenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. RESULTS: 473 pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95%CI=14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95%CI=8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95%CI=1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab/ocrelizumab showed a 2.3-fold lower gain (95%CI=1.4-3.8; p = 0.001), whereas, in contrast, those on fingolimod showed a 1.7-fold higher gain (95%CI: 1.1-2.7; p = 0.012), compared to patients treated with other DMTs. Conclusions All pwMS increased their serum SARS-CoV-2 antibodies levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical 'protective threshold' for risk of infection identified in the CovaXiMS study (> 659 BAU/mL), whereas for patients treated with fingolimod this value was significantly closer to the cut-off.

Factors Associated With Marshallese and Hispanic Adults' Willingness to Receive a COVID-19 Booster Dose.

INTRODUCTION/OBJECTIVES: New variants of the SARS-CoV-2 virus that causes COVID-19 will continue to develop and spread globally. The Omicron variant identified in November 2021 has many lineages. Variants spread quickly and can infect previously vaccinated individuals, prompting the Centers for Disease Control and Prevention to update vaccination recommendations. While ~230 million Americans received the initially-recommended vaccine sequence, booster uptake has been much lower; less than half of fully vaccinated individuals report receiving a booster. Racial disparities also mark patterns of COVID-19 vaccination booster uptake. This study explored willingness and motivations to get a COVID-19 booster among a diverse sample of participants. METHODS: We used convenience sampling to recruit participants 18 years of age or older who attended a community vaccine event. We conducted informal interviews during the recommended 15-min post-vaccination wait time with 55 participants who attended vaccine events at Marshallese and Hispanic community locations and comprised the recruitment pool for individual interviews. Using a qualitative descriptive design, we conducted in-depth follow-up interviews with 9 participants (Marshallese n = 5, Hispanic n = 4) to explore willingness and motivations to get boosted. We used rapid thematic template analysis to review informal interview summaries and formal interviews. The research team resolved data discrepancies by consensus. RESULTS: Participants reported high willingness to get boosted, especially if boosters were recommended in the future to protect against serious illness and mitigate the spread of COVID-19. This finding underscores how essential including recommendations to get a COVID-19 booster from trusted sources in health messaging and educational campaigns may be for increasing booster uptake. Participants described their preference for receiving future COVID-19 boosters, reporting that they would attend similar vaccine events, especially those held at faith-based organizations and facilitated by the same community partners, community health workers, and research staff. This finding shows how community engagement can overcome barriers to vaccination (ie, transportation, language, and fear of discrimination) by providing services in preferred community locations with trusted community partners. CONCLUSIONS: Findings document high willingness to get a COVID-19 booster, emphasize the role of recommendations from trusted sources in motivating booster uptake, and highlight the importance of community engagement to address disparities in vaccination coverage and reach.

REACTOGENICITY OF HETEROLOGOUS MRNA-BASED COVID-19 VACCINE BOOSTER IN YOUNG ADULTS IN INDONESIA- A SHORT COMMUNICATION.

Background: Heterologous priming with the inactivated SARS-CoV-2 vaccine (CoronaVac) and boosting with mRNA-based COVID-19 vaccine (Moderna or Pfizer) is currently recommended in Indonesia. The reactogenicity data of these heterologous vaccine regimens are not entirely available, particularly in young adults. The present study, therefore, aimed to evaluate the solicited local and systemic reactions in the first seven days post-vaccination either with Moderna or Pfizer vaccine among previous recipients of two doses of CoronaVac. Materials and Methods: An electronic-based cross-sectional study was conducted among medical students at the Pelita Harapan University, Banten, Indonesia, who received mRNA-based COVID-19 vaccine following two doses of CoronaVac. Samples were collected using a cluster sampling technique. Comparison between groups was performed by Fisher's exact test. Results: A total of 72 participants, 23 (32%) of which received the Moderna vaccine and 49 (68%) received the Pfizer vaccine, were included in this study. The median age of participants was 21 (IQR 19-22) years old. The most common local and systemic events for mRNA-based COVID-19 vaccines were injection site pain, fever, headache, fatigue, myalgia, and arthralgia. Solicited local and systemic reactions were reported more frequently in Moderna recipients than Pfizer recipients. Most local and systemic reactions were graded as mild to moderate and did not lead to hospitalization. Conclusions: The reactogenicity of the heterologous prime-boost with CoronaVac and mRNA-based COVID-19 vaccine booster among young adults is reassuring, and no unexpected concerns were identified.