Vaccine hesitancy is a key contributor to reduced COVID-19 vaccine uptake and remains a threat to COVID-19 mitigation strategies as many countries are rolling out the campaign for booster shots. The goal of our study is to identify and compare the top vaccine concerns in four countries: Canada, Italy, Sweden, and the USA and how these concerns relate to vaccine hesitancy. While most individuals in these countries are now vaccinated, we expect our results to be helpful in guiding vaccination efforts for additional doses, and more in general for other vaccines in the future. We sought to empirically test whether vaccine related concerns followed similar thematic issues in the four countries included in this study, and then to see how these themes related to vaccine hesitancy using data from a cross-sectional survey conducted in May 2021. We applied CFA and created vaccine concern scales for analysis. We then utilized these results in regression-based modeling to determine how concerns related to vaccine hesitancy and whether there were similar or different concerns by country. The results quantitatively highlight that the same vaccine related concerns permeated multiple countries at the same point in time. This implies that COVID-19 vaccination communications could benefit from global collaboration. Full article

The current report presents the case of a 76-year-old man with Parkinson’s disease (PD) who died three weeks after receiving his third COVID-19 vaccination. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov-19 vector vaccine, followed by two doses of the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to ambiguous clinical signs before death. PD was confirmed by post-mortem examinations. Furthermore, signs of aspiration pneumonia and systemic arteriosclerosis were evident. However, histopathological analyses of the brain uncovered previously unsuspected findings, including acute vasculitis (predominantly lymphocytic) as well as multifocal necrotizing encephalitis of unknown etiology with pronounced inflammation including glial and lymphocytic reaction. In the heart, signs of chronic cardiomyopathy as well as mild acute lympho-histiocytic myocarditis and vasculitis were present. Although there was no history of COVID-19 for this patient, immunohistochemistry for SARS-CoV-2 antigens (spike and nucleocapsid proteins) was performed. Surprisingly, only spike protein but no nucleocapsid protein could be detected within the foci of inflammation in both the brain and the heart, particularly in the endothelial cells of small blood vessels. Since no nucleocapsid protein could be detected, the presence of spike protein must be ascribed to vaccination rather than to viral infection. The findings corroborate previous reports of encephalitis and myocarditis caused by gene-based COVID-19 vaccines. Full article

Pneumococcal disease affects people across all ages but is more prevalent in young children and the elderly. Despite the availability of the pneumococcal vaccine for adults, the disease burden and mortality associated with it remains a challenge. A few studies conducted in Lebanon have reported epidemiology of pneumococcal disease, concurring the high burden among adults and older adults in the region. The pneumococcal vaccine is a part of the routine immunization schedule for children, but there are no recommendations for adult vaccination. A medical advisory board was hence conducted in September 2020 to discuss the burden of pneumococcal disease (PD) among adults in Lebanon. The participants were experts from the fields of internal medicine, family medicine, hematology, cardiology, oncology, endocrinology, pulmonology, and infectious diseases. The experts reached a consensus that there is a need to take steps to increase the rate of adult vaccination uptake and create awareness among physicians, pharmacists, caregivers, and patients. The physicians should be trained on adult immunization and should actively discuss the importance of the pneumococcal vaccine, especially with high-risk adult patients. Implementing adult vaccination as a routine practice and involving various stakeholders to address the gaps can help in reducing the burden of pneumococcal disease in adults. Full article

BNT162b2 (BioNTech/Pfizer) was the first SARS-CoV-2 mRNA vaccine approved by the European Medicines Agency. We monitored the long-term humoral responses of healthcare workers (HCWs) who received three vaccine doses. A total of 59 healthcare workers were studied: 47 were never SARS-CoV-2-infected (naïve-HCWs), and 12 (infected-HCWs) recovered from COVID-19 before the first vaccine. Serum and saliva were collected at baseline (before the first dose), just before the second dose, 1, 3, 6, and 9 months after the second dose, and 10 days after the third vaccine. SARS-CoV-2-specific IgG and IgA were evaluated in serum and saliva, respectively, and the presence of neutralizing antibodies (NAb) was analyzed in serum. SARS-CoV-2-specific IgG peaked one month after the second vaccine in naïve-HCWs but right before this timepoint in infected-HCWs. IgG titers significantly decreased during follow-up and at month 9 were still detectable in 50% of naïve-HCWs and 90% of infected-HCWs. NAb were significantly decreased 6 months after the second vaccine in naïve-HCWs and 9 months after this dose in infected-HCWs. Salivary SARS-CoV-2-specific IgA titers were significantly higher in infected-HCWs and were undetectable 9 months after the second vaccine in 43% of the naïve-HCWs alone. The third vaccine greatly increased humoral IgG and mucosal IgA in both groups. Two BNT162b2 doses induced strong systemic and humoral immune responses; to note, these responses weakened over time, although they are more prolonged in individuals who had recovered from COVID-19. The third vaccine dose quickly boosts systemic and mucosal humoral responses. Full article

Previous reports from our lab have documented dysregulated host inflammatory reactions in response to bacterial infections in sepsis. Both Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB) play a significant role in the development and progression of sepsis by releasing several virulence factors. During sepsis, host cells produce a range of inflammatory responses including inducible nitric oxide synthase (iNOS) expression, nitrite generation, neutrophil extracellular traps (NETs) release, and pro-inflammatory cytokines production. The current study was conducted to discern the differences in host inflammatory reactions in response to both Escherichia coli and Staphylococcus aureus along with the organ dysfunction parameters in patients of sepsis. We examined 60 ICU sepsis patients identified based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA II) scores. Pathogen identification was carried out using culture-based methods and gene-specific primers by real-time polymerase chain reaction (RT-PCR). Samples of blood from healthy volunteers were spiked with E. coli (GNB) and S. aureus (GPB). The incidence of NETs formation, iNOS expression, total nitrite content, and pro-inflammatory cytokine level was estimated. Prevalence of E. coli, A. baumannii (both GNB), S. aureus, and Enterococcus faecalis (both GPB) was found in sepsis patients. Augmented levels of inflammatory mediators including iNOS expression, total nitrite, the incidence of NETs, and proinflammatory cytokines, during spiking, were found in response to S. aureus infections in comparison with E. coli infections. These inflammatory mediators were found to be positively correlated with organ dysfunction in both GN and GP infections in sepsis patients. Augmented host inflammatory response was generated in S. aureus infections as compared with E. coli. Full article

Several cutaneous manifestations in patients undergoing COVID-19 vaccination have been described in the literature. Herein, we presented a case of new-onset vitiligo that occurred after the second dose of the Comirnaty vaccine. An updated literature search revealed the occurrence of a total of 16 cases, including new-onset or worsening of preexisting vitiligo. Given the autoimmune pathogenesis of the disease, we reviewed and discussed the potential role of the vaccine prophylaxis as a trigger for the development of such hypopigmented skin lesions. Full article

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12–18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID₅₀) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9–16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761–3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67–0.97) in 3wPZ30/20; 1.00 (95% CI 0.83–1.20) in 3wPZ20/20; 1.37 (95% CI 1.13–1.65) in 6wPZ30/30; 1.24 (95% CI 1.02–1.50) in 6wPZ30/20; and 1.36 (1.13–1.64) in 6wPZ20/20. After a booster dose with 15 μg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4–94.9) and 331 (95% CI 221–495), respectively. In the group that received 10 μg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0–91.6) and pVNT was 397 (95% CI 267–590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option. Full article

Healthcare workers (HCWs) are regarded as role models regarding health-related issues, including vaccination. Therefore, it is essential to identify the predictors for COVID-19 vaccine acceptance among them. A cross-sectional study to assess the risk perception, attitudes and knowledge of HCWs toward COVID-19 vaccination was carried out. A total of 710 responses were received between September 2021 and March 2022, from HCWs in the Northern, Western and Eastern regions of Nigeria. Cross tabulations were performed to determine statistical relations between sociodemographic variables, knowledge, attitudes and risk perceptions concerning COVID-19 vaccine acceptance. Multinomial logistic regression analysis was performed to determine the predictive variables for COVID-19 vaccine acceptance. Statistical analyses were performed and P-values less than 0.05 were considered statistically significant at a CI of 95%. Results showed that 59.3% of the participants were amenable to COVID-19 vaccines. Multinomial regression analysis identified 14 variables at α < 0.05 as predictors for vaccine acceptance. Male HCWs were 2.8 times more likely to accept the vaccine than their female counterparts. HCWs that were knowledgeable of the different kinds of vaccines, were willing to recommend the vaccines to their patients, believed that the timing of COVID-19 vaccination was appropriate and had recent vaccination history within three years were 1.6, 24.9, 4.4 and 3.1 times more likely to take COVID-19 vaccine than those not sure. The study found a relatively high trust (51.3%) in the Nigerian Center for Disease Control (NCDC) for information regarding COVID-19 vaccines. Therefore, the NDCD should disseminate more robust insights regarding the safety profiles of various COVID-19 vaccines. Full article

Four decades have passed since the first usage of the therapeutic vaccine in patients with chronic hepatitis B (CHB). However, there is no approved regimen of vaccine therapy for the treatment of CHB. This is mainly attributable to faulty conception, an improper understanding of the cellular and molecular mechanisms of CHB, and the impaired design of vaccine therapy for CHB. With the advent of new techniques and a better understanding of cellular and molecular mechanisms underlying the genesis of CHB, the limitations and failures of previous regimens of therapeutic vaccines have been primarily understood. Additionally, the importance of immune therapy for treating millions of CHB patients and achieving the target of “Elimination of Hepatitis by 2030” has been focused on in the international arena. This has been amplified by the apparent limitation of commercially available antiviral drugs that are infinite in duration, endowed with safety concerns, and unable to cure liver damage due to their minimal immune modulation capacities. The proposed review article comprehensively discusses each of these points and proposes evidence-based approaches for viable types of vaccine therapy for the treatment of CHB. Full article

Recent research has highlighted that a large section of druggable protein targets in the Human interactome remains unexplored for various diseases. It might lead to the drug repurposing study and help in the in-silico prediction of new drug-human protein target interactions. The same applies to the current pandemic of COVID-19 disease in global health issues. It is highly desirable to identify potential human drug targets for COVID-19 using a machine learning approach since it saves time and labor compared to traditional experimental methods. Structure-based drug discovery where druggability is determined by molecular docking is only appropriate for the protein whose three-dimensional structures are available. With machine learning algorithms, differentiating relevant features for predicting targets and non-targets can be used for the proteins whose 3-D structures are unavailable. In this research, a Machine Learning-based Drug Target Discovery (ML-DTD) approach is proposed where a machine learning model is initially built up and tested on the curated dataset consisting of COVID-19 human drug targets and non-targets formed by using the Therapeutic Target Database (TTD) and human interactome using several classifiers like XGBBoost Classifier, AdaBoost Classifier, Logistic Regression, Support Vector Classification, Decision Tree Classifier, Random Forest Classifier, Naive Bayes Classifier, and K-Nearest Neighbour Classifier (KNN). In this method, protein features include Gene Set Enrichment Analysis (GSEA) ranking, properties derived from the protein sequence, and encoded protein network centrality-based measures. Among all these, XGBBoost, KNN, and Random Forest models are satisfactory and consistent. This model is further used to predict novel COVID-19 human drug targets, which are further validated by target pathway analysis, the emergence of allied repurposed drugs, and their subsequent docking study. Full article

The aim of the study was to explore the humoral and T-cell response in lung transplant (LuT) patients. Two-time points were considered, before (T0) and after (Tpost) the third dose of the BNT162b2 mRNA vaccine, comparing LuT with healthy donors (HD). LuT patients showed a lower serologic response against SARS-CoV-2 compared with HD at both time-points (p = 0.0001 and p = 0.0011, respectively). A lower percentage of IFNγ+orIL2+orTNFα+CD4+ and CD8+ T-cells LuT patients was observed in LuT patients compared with HD at T0 (CD4+: p = 0.0001; CD8+: p = 0.0005) and Tpost (CD4+: p = 0.0028; CD8+: p = 0.0114), as well as in the percentage of IFNγ+IL2+TNFα+CD4+ T-cells (T0: p = 0.0247; Tpost: p = 0.0367). Finally, at Tpost, a lower percentage of IFNγ+IL2+TNFα+ CD8+ T-cells in LuT patients compared with HD was found (p = 0.0147). LuT patients were stratified according to the lowest cut-off value for the detection of a humoral response (4.81 BAU/mL) at T0, into responder (R) and non-responder (NR) groups. In the R group, no differences in the percentage of IFNγ+or IL2+orTNFα+ and IFNγ+IL2+TNFα+CD4+ and CD8+ T-cells compared with HD at both time-points were observed. Otherwise, in the NR group, lower percentages of IFNγ+IL2+TNFα+CD4+ T-cells compared with the R group (T0: p = 0.0159; Tpost: p = 0.0159), as well as compared with the HD, at both time-points, were observed (T0: p = 0.0064; Tpost: p = 0.0064). These data seem to confirm that some LuT patients can mount cellular responses even in the absence of a positive humoral response (>33.8 BAU/mL), although this cellular response is dysfunctional and partially detrimental. Full article

Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2. Full article

Vaccine hesitancy is widespread in many parts of the globe, particularly in low–middle-income countries. Therefore, we surveyed a sample of hospitalized COVID-19 patients to assess COVID-19 vaccine acceptance and vaccine hesitancy in a low–middle-income country. A cross-sectional sample of 385 confirmed reverse transcriptase–polymerase chain reaction COVID-19 patients treated at secondary and tertiary care hospitals in Punjab, Pakistan, were analyzed to assess COVID-19 vaccine uptake and vaccine hesitancy. The construct validity and reliability of the 11-item vaccine hesitancy questionnaire were also examined. In addition, multivariate logistic regression was used. The majority of the COVID-19 patients admitted to hospitals were not vaccinated (84%). Of those who were willing to receive vaccination, the majority (55%) considered vaccines an effective way to protect people from COVID-19. However, those who were not willing to receive their COVID-19 vaccine had significantly higher hesitancy than those willing to receive their COVID-19 vaccine. In addition, older hospitalized COVID-19 patients aged 60 years or above (20–29 years: OR 0.10; 95% CI 0.01–0.72, p = 0.001) and patients from urban areas (OR 3.16 95% CI 1.27–7.87, p = 0.013) were more likely to receive the COVID-19 vaccine than younger patients and patients from rural areas. Patients with no formal education had significantly higher hesitancy (OR 5.26; 96% CI 1.85–14.97, p = 0.002) than participants with graduation and above education. More than half of the study’s participants did not trust information shared on social media about COVID-19 vaccines and cited newspapers/news channels as their main source of information. The study provides important insights into COVID-19 vaccine acceptance and the impact of vaccination campaigns. Many unvaccinated COVID-19 patients in hospitals highlight the need for an effective vaccination drive to protect people from acquiring infection and subsequent hospitalization. Full article

Over the past two years, SARS-CoV-2 has dramatically spread worldwide and emerged as a major pandemic which has left an unprecedented mark on healthcare systems and economies worldwide. As our understanding of the virus and its epidemiology continues to grow, the acute phase clinical symptoms and long-term and vaccine-related complications are becoming more apparent. With heterogeneity in presentations, comparisons may be drawn between COVID-19-related sequelae and vaccination related adverse events. The present review article aims to address the currently available literature on the SARS-CoV-2 virus, immune responses, the pathophysiology of clinical presentations, and available vaccinations with its adverse events for the appraisal of its potential impact on the COVID-19 management system. Full article

Background: Research shows that in most people, two-dose vaccination helps to shape the humoral response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Further studies are required to learn about the vaccine’s effectiveness after boosting. Methods: We conducted a prospective study among 103 healthcare workers (HCWs) from a regional multi-specialty hospital vaccinated with three doses of the BNT162b2 vaccine. We compared their immunoglobulin G (IgG) titers 14 days after the second dose with those 21 days after the booster. We also compared their anthropometric and body composition parameters with IgG concentrations at the same time points. Results: Twenty-one days after the booster, all study participants were seropositive. Their mean IgG antibody titers were significantly lower than 14 days after the second dose (158.94 AU/mL ± 90.34 AU/mL vs. 505.79 AU/mL ± 367.16 AU/mL). Post-booster Spearman’s correlation analysis showed a significantly weak correlation between the IgG antibody titer and parameters related to muscle tissue and adipose tissue (including body fat mass). Conclusions: The BNT162b2 booster stimulates the humoral response to a lesser extent than the two-dose BNT162b2 primary vaccination. The adipose and muscle tissue parameters show a weak positive correlation with the SARS-CoV-2 IgG antibody titers. Full article