Relief After COVID-19 Vaccination: A Doubtful or Evident Outcome?

Background: Since development of the first COVID-19 vaccine, the landscape of public confidence in these vaccines is uncertain. Building confidence is crucial for better preparedness of future pandemics. Following the mandatory COVID-19 vaccination policy in the country, the aim of this study was to examine whether the Saudi public feels relieved post-vaccination and to identify the factors predicting such relief.Methods: An online cross-sectional survey was conducted in July 2021 among COVID-19 vaccine recipients in Saudi Arabia. A multivariable logistic regression analysis was employed to examine and identify the variables associated with feeling relieved post-vaccination.Results: Most of the respondents (66%) stated feeling more relieved post-vaccination. Male gender [adjusted odds ratio (AOR): 1.380; 95% confidence interval (CI): 0.981–1.943], being a student (AOR: 3.902; 95% CI: 1.674–9.096), and received two doses of the vaccine (AOR: 2.278; 95% CI: 1.630–3.182) were associated with feeling more relieved after getting vaccinated. Respondents who were anxious about the vaccine before receiving it (AOR: 0.220; 95% CI: 0.160–0.302), and experienced a severe reaction after vaccination (AOR: 0.288; 95% CI: 0.165–0.504) had lower odds of feeling relieved post-vaccination. Respondents who relied on social media as the main source of vaccine-related information and those having no information about the vaccine were also less likely to feel relieved post-vaccination.Conclusions: Individuals' attitudes toward COVID-19 vaccines may not necessarily alter post-vaccination. Although mandatory vaccination policies can significantly contribute to achieving herd immunity, public confidence toward vaccines might be eroded, which could in turn impose significant challenges in future pandemics efforts.

Clinical and Laboratory Profile of Patients With Anaphylaxis to Fire Ant Venom (Solenopsis Sp) Under Specific Subcutaneous Immunotherapy.

Anaphylaxis to fire ant venoms (Solenopsis sp) is a significant cause of systemic allergic reaction caused by Hymenoptera stings in children. There are only a few reports about the safety and efficacy of specific immunotherapy. We aim evaluate clinical characteristics, IgE and IgG4 specific responses of patients undergoing immunotherapy with a whole-body extract of Solenopsis sp after one year of the maintenance phase. Thirty-three patients were enrolled due to anaphylaxis by fire ant venom (Solenopsis sp) and underwent specific venom immunotherapy. They were assessed at baseline and one year after the beginning of the maintenance phase for skin test; specific IgE and IgG4 antibodies to fire ant venom; tryptase. All patients included presented a severe anaphylactic reaction. Although two patients (6.25%) presented a tryptase level higher than 11.4 ug/ml, systemic mastocytosis was ruled out. There was no relationship between the severity of the reaction with gender, tryptase level, atopy, previous reactions, concentration of the allergen in the skin test or specific IgE level. There was an increase of the specific IgG4/IgE ratio between the two time points. Reactions were local, with only two mild systemic reactions during the build-up phase. Twenty patients had accidental stings during immunotherapy, with 3 presenting only urticaria. This study is unprecedented in evaluating clinical and laboratory data in the fire ant immunotherapy. Our results show that after one year of the maintenance phase, patients did not develop any severe reaction with only a few mild reactions and presented a significant production of specific IgG4.

Drug reexposure in children with severe mucocutaneous reactions

In pediatric patients, severe cutaneous adverse reactions (SCARs) frequently occur in the course of acute illnesses, mostly infections, which are usually treated with antibiotics or analgesics. The drug provocation test (DPT) is contraindicated in such situations, due to the risk of triggering a new severe reaction. As a consequence, lifelong avoidance is recommended. However, causation is uncertain in most cases. The dilemma arises when avoiding the drug is not harmless for the patient. We have attended three patients who were referred to our pediatric allergy unit with a history of SCAR related in time to simultaneous use of paracetamol and ibuprofen. Medical records and images of the patients were reviewed with the assistance of a dermatologist, and alternative diagnoses were considered in both cases. The ALDEN score for implicated drugs was calculated. After considering a high probability of ibuprofen tolerance and obtaining informed consent from the patients, we performed a sequential allergy workup including in vitro tests, skin tests, and finally DPT in two of the patients, confirming ibuprofen tolerance. In conclusion, although generally contraindicated, DPT may be considered for some useful drugs after careful evaluation of the risk–benefit balance, preceded by a sequential study including in vitro and skin tests.

Factors Associated with Adverse Reactions to BNT162b2 COVID-19 Vaccine in a Cohort of 3969 Hospital Workers

Factors associated with adverse reactions to BNT162b2 COVID-19 vaccine reported by hospital workers are unclear. Our aim was to collect all reported adverse events in a cohort of hospital workers and to analyze the factors associated with their presence. We conducted an observational longitudinal study on all hospital workers of our center who received COVID-19 vaccination from 27 December 2020 to 1 September 2021. Information on adverse events was reported telephonically and confirmed through clinical records. Chi-square and t tests as well as multivariate logistic regression models were used. Cluster analysis was designed to explore associations between reactions. A total of 3969 hospital workers were included in the sample. Of the total sample, 182 workers (4.6%) reported adverse events. The most frequent symptoms were general malaise (n = 95), fever (n = 92), arthromyalgia (n = 80), and headache (n = 47). The factors associated with adverse events in adjusted analyses were an antecedent of COVID-19 infection (OR = 2.09, 95% CI: 1.47–2.98), female sex (OR = 1.51, 95% CI: 1.03–2.20), and professional category (OR for physicians = 0.41, 95% CI: 0.21–0.80). We report a low frequency of adverse events in hospital workers after COVID-19 vaccination and no severe reaction. Men and physicians underreported their symptoms. These data should guide future strategies for recording adverse events and future research on COVID-19 vaccination safety.

Dietary exposures and allergy prevention in high-risk infants

Infants at high risk for developing a food allergy have either an atopic condition (such as eczema) themselves or an immediate family member with such a condition. Breastfeeding should be promoted and supported regardless of issues pertaining to food allergy prevention, but for infants whose mothers cannot or choose not to breastfeed, using a specific formula (i.e., hydrolyzed formula) is not recommended to prevent food allergies. When cow’s milk protein formula has been introduced in an infant’s diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance. For high-risk infants, there is compelling evidence that introducing allergenic foods early—at around 6 months, but not before 4 months of age—can prevent common food allergies, and allergies to peanut and egg in particular. Once an allergenic food has been introduced, regular ingestion (e.g., a few times a week) is important to maintain tolerance. Common allergenic foods can be introduced without pausing for days between new foods, and the risk for a severe reaction at first exposure in infancy is extremely low. Pre-emptive in-office screening before introducing allergenic foods is not recommended. No recommendations can be made at this time about the role of maternal dietary modification during pregnancy or lactation, or about supplementing with vitamin D, omega 3, or pre- or probiotics as means to prevent food allergy.

Prototheca spp. induce an inflammatory response via mtROS-mediated activation of NF-κB and NLRP3 inflammasome pathways in bovine mammary epithelial cell cultures

Emergence of bovine mastitis caused by Prototheca algae is the impetus to better understand these infections. Both P. bovis and P. ciferrii belong to Prototheca algae, but they differ in their pathogenicity to induce inflammatory responses. The objective was to characterize and compare pathogenesis of inflammatory responses in bMECs induced by P. bovis versus P. ciferrii. Mitochondrial ultrastructure, activity and mtROS in bMECs were assessed with transmission electron microscopy and laser scanning confocal microscopy. Cytokines, including TNF-α, IL-1β and IL-18, were measured by ELISA and real-time PCR, whereas expressions of various proteins in the NF-κB and NLRP3 inflammasome pathways were detected with immunofluorescence or Western blot. Infection with P. bovis or P. ciferrii damaged mitochondria, including dissolution and vacuolation of cristae, and decreased mitochondrial activity, with P. bovis being more pathogenic and causing greater destruction. There were increases in NADPH production and mtROS accumulation in infected bMECs, with P. bovis causing greater increases and also inducing higher cytokine concentrations. Expressions of NF-κB-p65, p-NF-κB-p65, IκBα and p-IκBα proteins in the NF-κB pathway, as well as NLRP3, Pro Caspase1, Caspase1 p20, ASC, Pro IL-1β, and IL-1β proteins in the NLRP3 inflammasome pathway, were significantly higher in P. bovis-infected bMECs. However, mito-TEMPO significantly inhibited production of cytokines and decreased expression of proteins in NF-κB and NLRP3 inflammasome pathways in bMECs infected with either P. bovis or P. ciferrii. In conclusion, P. bovis or P. ciferrii infections induced inflammatory responses in bMECs, with increased mtROS in damaged mitochondria and activated NF-κB and NLRP3 inflammasome pathways, with P. bovis causing a more severe reaction.

Assessment of Inflammatory Response on Pyrogenic Induction by In vitro and In vivo Methods

The incidence of pyrogenic contaminations creates a paramount safety concern in the field of biotherapeutics, as it compromises the normal well-being of an individual. After exposure to pyrogenic agents, the febrile response can create a severe reaction from shock and further complications leading to death. So it is imperative that the medical aids, as well as the parenteral drugs, must be pyrogen-free. The possible reliability of continuous supply of healthy human blood can be overcome by implementing a novel approach by pooling the blood samples for checking the pyrogenicity. In this study, an indigenously developed sandwich ELISA method to quantify pro-inflammatory cytokine (IL-1β) activated after pyrogenic exposure was used. The study unraveled the possibility of using the human pooled blood system to detect the endogenous pyrogen (IL-β) after exposure to endotoxins from Gram-positive and negative bacteria and chemical toxicants such as phytohemagglutinin (PHA) and 2,4,6-trinitrophenol (TNP). The results indicate that upon exposure to the high concentration of endotoxin such as LPS (5EU/ml) and LTA (1µg/ml), the maximum release of IL-1β was observed within 2h of post-stimulation. The stimulation with chemical toxicants PHA and TNP triggered a sudden release of IL-1β within 2h in both cases after 30µg/ml treatment. The study conveys a better platform for providing a continuous supply of healthy human blood, thus minimizing personal variations for the detection of IL-1β for evaluating in vitro pyrogenic response. It also depicts understanding the possible underlying mechanism of the pyrogenic response level of inflammatory cytokines and the possible rise in biochemical parameters leading to complications that affect the normal homeostasis by lipopolysaccharide-induced in rabbits.

Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults

M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects.

HLA-A*03:01 is associated with increased risk of fever, chills, and more severe reaction to Pfizer-BioNTech COVID-19 vaccination

COVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the US have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination. Our GWAS identifies an association between severe vaccine side effects and HLA-A*03:01. This association was statistically significant only for those who received the Pfizer-BioNTech vaccine (BNT162b2; p=4.70E-11), but showed a trending association in those who received the Moderna vaccine (mRNA-1273; p=0.005) despite similar sample sizes for study. In Pfizer-BioNTech recipients, HLA-A*03:01 was associated with a two-fold increase in risk of severe vaccine side effects. The effect was consistent across ages, sexes, and whether the person had previously had a COVID-19 infection. The reactions experienced by HLA-A*03:01 carriers were driven by associations with chills, fever, fatigue, and in general feeling unwell.

COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis

Background and ObjectivesThere are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis–specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.MethodsBetween 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity.ResultsIn 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction.DiscussionSARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.