Search Results (90)

Background: The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or severe COVID-19, both in individuals who had completed their primary COVID-19 vaccination, and in those who had received their first booster vaccination. Specifically, we aimed to evaluate whether persons with certain risk factors, such as age, gender, socioeconomic status (SES), and specified comorbidities have an increased risk of either breakthrough infection or severe COVID-19, compared to those without the respective risk factors. Methods: Data on COVID-19 vaccinations, infections, hospitalizations, and deaths were collected from the PHARMO Data Network, consisting of health records from Dutch residents. Two cohorts were established: (1) all persons who have completed their primary COVID-19 vaccination regimen, and (2) those who have received their first booster vaccination. The outcomes were SARS-CoV-2 breakthrough infection, and severe COVID-19, defined as either hospitalization or death following SARS-CoV-2 infection. Incidence rates of these outcomes were calculated in both cohorts. The adjusted incidence rate ratios of these outcomes in persons with certain risk factors were calculated, using generalized linear models with a Poisson distribution. Results: In 2021, a total of 1,090,567 individuals received either two doses of BNT162b2, AZD1222, or mRNA-1273, or one dose of Ad26.COV2.S and were included in the primary vaccination cohort, of which 344,153 (31.6%) received a booster vaccination. Overall incidence rates of SARS-CoV-2 breakthrough infection and severe COVID-19 after primary vaccination were 29.9 and 3.1 per 1000 person-years, respectively, and after booster vaccination were 256.4 and 2.3, respectively. Male gender, older age, lower SES, history of COVID-19, and recent hospitalization were factors associated with a lower risk of breakthrough infection after primary vaccination, and a higher risk of severe COVID-19. The risk of severe COVID-19 after primary vaccination was increased in persons with several comorbidities, compared to those without, and remained elevated after booster vaccination in persons with diabetes or lung disease. Conclusions: Our study emphasizes the crucial role of boosters in reducing breakthrough infections, particularly in high-risk populations. The varied impact on severe outcomes in individuals with comorbidities underscores the need for ongoing surveillance and tailored vaccination strategies. Full article

The rapid evolution of SARS-CoV-2 has led to the emergence of variants with increased immune evasion capabilities, posing significant challenges to antibody-based therapeutics and vaccines. In this study, we conducted a comprehensive structural and energetic analysis of SARS-CoV-2 spike receptor-binding domain (RBD) complexes with neutralizing antibodies from four distinct groups (A–D), including group A LY-CoV016, group B AZD8895 and REGN10933, group C LY-CoV555, and group D antibodies AZD1061, REGN10987, and LY-CoV1404. Using coarse-grained simplified simulation models, rapid energy-based mutational scanning, and rigorous MM-GBSA binding free energy calculations, we elucidated the molecular mechanisms of antibody binding and escape mechanisms, identified key binding hotspots, and explored the evolutionary strategies employed by the virus to evade neutralization. The residue-based decomposition analysis revealed energetic mechanisms and thermodynamic factors underlying the effect of mutations on antibody binding. The results demonstrate excellent qualitative agreement between the predicted binding hotspots and the latest experiments on antibody escape. These findings provide valuable insights into the molecular determinants of antibody binding and viral escape, highlighting the importance of targeting conserved epitopes and leveraging combination therapies to mitigate the risk of immune evasion. Full article

Background/Objectives: Understanding the behavior of B cells during infection and vaccination is important for determining protective humoral immunity. We evaluated the profile of humoral immunity and B cell pool in individuals who were acutely infected with SARS-CoV-2, recovered from COVID-19, or received two doses of the AZD1222 vaccine. Methods: Peripheral blood mononuclear cells (PBMCs) from these individuals were subjected to in vitro stimulation to promote the differentiation of B cells into antibody-secreting cells (ASCs), and the ELISpot evaluated the abundance of pan and SARS-CoV-2 Spike S1-reactive IgG+ ASC. Stimulated PBMCs were characterized using flow cytometry. Culture supernatants were assessed for soluble B-cell-activating factors. The IgA and IgG for the S1 were evaluated through ELISA. Results: The recovered individuals displayed a robust S1 ASC compared to acute and vaccinated individuals. Although the frequency of total B cells or B cell subsets did not vary among the groups, plasmablast cells were increased in naïve and double-negative B cells in the acute, recovered, and vaccinated individuals. Similar IgA and IgG production appeared to be present in the acute and recovered individuals. During vaccination, more IgG is produced than IgA. In acute patients, BAFF levels were positively correlated with total B cells and IgG+ plasmablast cells but negatively correlated with IgA+ plasmablast cells. Conclusions: Vaccination and natural infection with COVID-19 induce a differential profile and functionality of B cells. We suggest that new vaccines against COVID-19 incorporate molecular adjuvants that regulate B lymphocyte functionality and consider the beneficial aspects of the IgA response in addition to IgG. Full article

Background: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses. In this regard, global research has primarily focused on mRNA-based vaccines. The studies on immune memory response, particularly B cell memory response induced by the vaccines given to Indians, remain relatively obscure. Methods: We assessed Receptor Binding Domain-specific memory B cells in the peripheral circulation and their ability to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D), and Sputnik Light, as well as unvaccinated individuals. Results: Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses over time compared to other groups. Conclusions: These findings contribute to our understanding of vaccine-induced immune memory in the Indian population; providing insights that could inform future vaccine strategies. Full article

Vaccine effectiveness (VE) studies provide real-world evidence to monitor vaccine performance and inform policy. The WHO Regional Office for the Eastern Mediterranean supported a regional study to assess the VE of COVID-19 vaccines against different clinical outcomes in four countries between June 2021 and August 2023. Health worker cohort studies were conducted in 2707 health workers in Egypt and Pakistan, of whom 171 experienced symptomatic laboratory-confirmed SARS-CoV-2 infection. Test-negative design case–control studies were conducted in Iran and Jordan in 4017 severe acute respiratory infection (SARI) patients (2347 controls and 1670 cases) during the Omicron variant dominant period. VE estimates were calculated for each study and pooled by study design for several vaccine types (BBIBP-CorV, AZD1222, BNT162b2, and mRNA-1273, among others). Among health workers, VE against symptomatic infection of a complete primary series could only be computed compared to partial vaccination, suggesting a benefit of providing an additional dose of mRNA vaccines (VE: 88.9%, 95%CI: 15.3–98.6%), while results were inconclusive for other vaccine products. Among SARI patients, VE against hospitalization of a complete primary series with any vaccine compared to non-vaccinated was 20.9% (95%CI: 4.5–34.5%). Effectiveness estimates for individual vaccines, booster doses, and secondary outcomes (intensive care unit admission and death) were inconclusive. Future VE studies will need to address challenges in both design and analysis when conducted late during a pandemic and will be able to utilize the strengthened capacities in countries. Full article

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity. Full article

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld^®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study’s non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children. Full article

Abdominal obesity is highly prevalent in Mexico and has a poor prognosis in terms of the severity of coronavirus disease (COVID-19) and low levels of antibodies induced by infection and vaccination. We evaluated the humoral immune response induced by COVID-19 and five different vaccination schedules in Mexican individuals with abdominal obesity and the effects of other variables. This prospective longitudinal cohort study included 2084 samples from 389 participants. The levels of anti-S1/S2 and anti-RBD IgG antibodies were measured at various time points after vaccination. A high prevalence of hospitalization and oxygen use was observed in individuals with abdominal obesity (AO) who had COVID-19 before vaccination; however, they also had high levels of anti-S1/S2 and anti-RBD-neutralizing IgG antibodies. The same was true for vaccination-induced antibody levels. However, their longevity was low. Interestingly, we did not observe significant differences in vaccine reactogenicity between abdominally obese and abdominally non-obese groups. Finally, individuals with a higher body mass index, older age, and previous COVID-19 had higher levels of antibodies induced by COVID-19 and vaccination. Therefore, it is important to evaluate other immunological and inflammatory factors to better understand the pathogenesis of COVID-19 in the presence of risk factors and to propose effective vaccination schedules for vulnerable populations. Full article

Background: Given the impact of the pandemic in Brazil, vaccination is essential to prevent illness and death. Thus, this study sought to compare, after vaccination, the circulation of SARS-CoV-2 and the response to vaccination in the least and most vaccinated municipalities of a Brazilian state during the height of the pandemic when the Omicron variant was dominant. Methods: We tested for the SARS-CoV-2 antigen and confirmed infection using an RT-qPCR and measured IgM and IgG antibodies in fully vaccinated participants from municipalities with higher and lower vaccination rates. Results: We showed that participants from the least vaccinated municipalities were more likely to have detectable IgM antibodies and a positive antigen/RT-qPCR result for SARS-CoV-2 than participants from the most vaccinated municipalities. There were no differences between the vaccines used (BNT162b2, Ad26.COV2.S, AZD1222, and CoronaVac) and antibody production. Conclusions: Our study evaluated municipal vaccination coverage and its effects on mortality, infections, and anti-SARS-CoV-2 antibodies during a critical phase of the pandemic. The results suggest that higher vaccination coverage reduces acute cases and confers higher memory antibody levels against SARS-CoV-2. Even with a full vaccination schedule, individuals living in places with low vaccination rates are more susceptible to infection. Full article

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare autoimmune condition associated with recombinant adenovirus (rAV)-based COVID-19 vaccines. It is thought to arise from autoantibodies targeting platelet factor 4 (aPF4), triggered by vaccine-induced inflammation and the formation of neo-antigenic complexes between PF4 and the rAV vector. To investigate the specific induction of aPF4 by rAV-based vaccines, we examined sera from rAV vaccine recipients (AZD1222, AD26.COV2.S) and messenger RNA (mRNA) based (mRNA-1273, BNT162b2) COVID-19 vaccine recipients. We compared the antibody fold change (FC) for aPF4 and for antiphospholipid antibodies (aPL) of rAV to mRNA vaccine recipients. We combined two biobanks of Dutch healthcare workers and matched rAV-vaccinated individuals to mRNA-vaccinated controls, based on age, sex and prior history of COVID-19 (AZD1222: 37, Ad26.COV2.S: 35, mRNA-1273: 47, BNT162b2: 26). We found no significant differences in aPF4 FCs after the first (0.99 vs. 1.08, mean difference (MD) = −0.11 (95% CI −0.23 to 0.057)) and second doses of AZD1222 (0.99 vs. 1.10, MD = −0.11 (95% CI −0.31 to 0.10)) and after a single dose of Ad26.COV2.S compared to mRNA-based vaccines (1.01 vs. 0.99, MD = 0.026 (95% CI −0.13 to 0.18)). The mean FCs for the aPL in rAV-based vaccine recipients were similar to those in mRNA-based vaccines. No correlation was observed between post-vaccination aPF4 levels and vaccine type (mean aPF difference −0.070 (95% CI −0.14 to 0.002) mRNA vs. rAV). In summary, our study indicates that rAV and mRNA-based COVID-19 vaccines do not substantially elevate aPF4 levels in healthy individuals. Full article

The safety profiles of the Ad26.COV2.S and AZD1222 COVID-19 vaccines have not been described in the general population in Malawi. We present self-reported adverse events (AE) following the receipt of these vaccines in Malawi as part of a national syndromic surveillance survey. We conducted phone-based syndromic surveillance surveys among adults (≥18 years) with verbal consent. We used secure tablets through random digit dialing to select mobile phone numbers and collected data electronically. Survey questions included whether the respondent had received the COVID-19 vaccines, whether they had experienced any AE following vaccination, and the severity of the AE. We used multivariable analysis to identify factors associated with self-reported AE post-COVID-19 vaccination. A total of 11,924 (36.0%) out of 33,150 respondents reported receiving at least one dose of either Ad26.COV2.S or AZD1222 between July–December 2021; of those, 65.1% were female. About 49.2% of the vaccine recipients reported at least one AE, 90.6% of which were mild, and 2.6% were severe. Higher education level and concern about the safety of COVID-19 vaccines were associated with AE self-report (Adjusted Odds Ratio [AOR] 2.63 [95% CI 1.96–3.53] and 1.44, [95% CI 1.30–1.61], respectively), while male gender and older age were associated with reduced likelihood of AE self-report (AORs 0.81, [95% CI 0.75–0.88], 0.62 [95% CI 0.50–0.77], respectively). Ad26.COV2.S and AZD1222 vaccines are well-tolerated, with primarily mild and few severe AE among adults living in Malawi. Self-reporting of AE following COVID-19 vaccination is associated with gender, age, education, and concern about the safety of the vaccines. Recognizing these associations is key when designing and implementing COVID-19 vaccination communication messages to increase vaccination coverage. Full article

Background: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. Methods: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. Results: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8–64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3–79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3–87.3). VE was highest, at 60.7% (95% CI: 23.6–81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6–75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). Conclusions: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV. Full article

Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89–94% in MB and 82–89% in CB for Omicron subvariants. Those receiving AZD1222 vaccines in previous monovalent vaccination demonstrated poorer maternal Nab inhibition of BA.5, BQ.1, and XBB.1.5 than others. Poorer maternal Nab inhibition of BA.5, BF.7, and BQ.1 was found in those receiving two-dose AZD1222 vaccinations than with either one or no AZD1222 vaccination. MB from those with infants weighing < 3100 g demonstrated better Nab inhibition of BF.7 than those > 3100 g (97.99 vs. 95.20%, p = 0.048), and there were also similar trends for Nab inhibition of BA.5 and BQ.1. No significant differences were seen in CB samples. Although diminished maternal Nab inhibition was seen in those with previous monovalent AZD1222 vaccination and heavier newborns, neonatal Nab inhibition was still strong after bivalent COVID-19 booster vaccination. Full article

Background: Four vaccines have been authorized by the European Medicines Agency (EMA): viral vector-based vaccines (AstraZeneca; AZD1222 and Johnson & Johnson; Ad26.COV2. and 2 mRNA-based vaccines (Pfizer/BioNTech; BNT162b2 and Moderna; mRNA-1273). Adverse events (AEs) related to vaccination have been described in the literature. The main aim of the dermatological practice was to avoid the diffusion of COVID-19, allowing the continuity of care for patients. Objective: The aim of this review article is to investigate current literature regarding cutaneous reactions following COVID-19 vaccination, mainly inflammatory dermatological diseases. Materials and methods: Investigated manuscripts included metanalyses, reviews, letters to the editor, real-life studies, case series, and reports. Results: We selected a total of 234 articles involving more than 550 patients. We have divided the results section into various sub-sections to ensure greater understanding for readers. Conclusions: Clinicians should keep in mind the possibility of new onsets or the worsening of several dermatoses following vaccination in order to promptly recognize and treat these AEs. Certainly, vaccination should not be discouraged. Full article

(1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were tested for IgM/IgG antibodies to the SARS-CoV-2 spike protein with the STANDARD™ Q COVID-19 IgM/IgG Plus Test (QNCOV-02C). ELISA/competitive inhibition ELISA (CI-ELISA) was subsequently run to assess the validity of the serological antibody test. (3) Results: The sensitivity of homeless people was 43.5%. The status of homelessness was related to a lower agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 0.35; 95% CI, 0.18–0.70). However, the Heterologous boost vaccine presented higher agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 6.50; 95% CI, 3.19–13.27). (4) Conclusions: This study found weak agreement between the rapid IgG results and confirmatory CI-ELISA testing in homeless people. However, it can be used as a screening test for the acceptance of homeless people with heterologous boost vaccination in facilities. Full article