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1.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202212.0382.v2

ABSTRACT

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p < 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p < 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.


Subject(s)
Necrosis , Drug Hypersensitivity
3.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2362385.v1

ABSTRACT

Background Traditional Chinese medicine (TCM) has potential benefits to prevent multi-viral infection including by modulating the immune system or defending oxidative stress. Artemisia argyi (A. argyi) has been widely used for anti-microbial infection, anti-allergy, anti-diabetes, and anti-inflammation in Eastern Asia. However, it remain unclear whether A. argyi has the potential to reduce the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Results Through the docking simulation, eriodictyol and umbelliferone, two phytochemicals existed in Artemisia argyi, have showed their potential to bind to cellular proteins transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of SARS-CoV-2. Our results further found that eriodictyol and umbelliferone suppressed the infection of ACE2-expressed HEK-293T cells with lentiviral-based pseudo-particles expressing wild type and variants of SARS-CoV-2 spike (S) protein via interrupting the interaction between S protein and cellular receptor ACE2 and via reducing ACE2 and TMPRSS2 expressions.Conclusions In summary, Artemisia argyi and its ingredients eriodictyol and umbelliferone are potential agents to reduce SARS-CoV-2 infection.


Subject(s)
Coronavirus Infections , COVID-19 , Drug Hypersensitivity , Severe Acute Respiratory Syndrome , Virus Diseases , Diabetes Mellitus , Inflammation
4.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.12.06.22283145

ABSTRACT

Introduction: Serious harms of the COVID-19 vaccines have been underreported in published trial reports. Methods: Systematic review of papers with data on serious adverse events (SAEs) associated with a COVID-19 vaccine. Results: We included 18 systematic reviews, 14 randomised trials, and 34 other studies with a control group. Most studies were of poor quality. The most reliable one was a systematic review of regulatory data on the two pivotal randomised trials of the mRNA vaccines. It found significantly more SAEs of special interest with the vaccines than with placebo, and the excess risk was considerably larger than the benefit, measured as the risk of hospitalisation. The adenovirus vector vaccines increased the risk of venous thrombosis and thrombocytopenia, and the mRNA-based vaccines increased the risk of myocarditis, with a mortality of about 1-2 per 200 cases. We also found evidence of serious neurological harms, including Bel's palsy, Guillain-Barre syndrome, myasthenic disorder and stroke, which are likely due to an autoimmune reaction, as has been suggested also for the HPV vaccines. Severe harms, i.e. those that prevent daily activities, were hugely underreported in the randomised trials. These harms were very common in studies of booster doses after a full vaccination and in a study of vaccination of previously infected people. Discussion: Serious and severe harms of the COVID-19 vaccines have been ignored or downplayed, and sometimes been deliberately excluded by the study sponsors in high impact medical journals. This area needs further study. Authorities have recommended virtually everyone get vaccinated and receive booster doses. They fail to consider that the balance between benefits and harms becomes negative in low-risk groups such as children and people who have already acquired natural immunity.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Venous Thrombosis , COVID-19 , Myasthenic Syndromes, Congenital , Drug Hypersensitivity , Thrombocytopenia , Guillain-Barre Syndrome , Hallucinations , Myocarditis , Stroke
5.
authorea preprints; 2022.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.167025801.11761331.v1

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.


Subject(s)
Heart Diseases , Multiple System Atrophy , Coronavirus Infections , Child Nutrition Disorders , COVID-19 , Drug Hypersensitivity , Pediatric Obesity , Cryopyrin-Associated Periodic Syndromes , Immune System Diseases
6.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.11.24.516986

ABSTRACT

Polyethylene glycol (PEG)-conjugated lipid has significantly contributed to the success of three approved lipid nanoparticles (LNP)-delivered therapeutics, particularly two COVID-19 mRNA vaccines. It is known that some PEG derivatives could elicit anti-PEG antibodies and subsequently form “antigen-antibody” complexes with newly injected PEGylated agents, leading to pharmacokinetic changes, reduced therapeutic efficacy and even hypersensitivity reactions. With the large-scale vaccination of mRNA vaccines, it has become an imminent task to elucidate the possible PEG-associated immunological effects induced by clinically relevant LNP. Up to date there are only four related studies, all of which are clinical observations emphasizing on the changes of PEG-specific antibodies upon injection of mRNA vaccines. Unfortunately, contradictory and inconclusive data were obtained due to significant person-to-person and study-to-study variabilities. To clarify the PEG-associated immunological effects of clinically relevant LNP in a model system with least “noise”, we initiated an animal study using the PEGylated LNP of BNT162b2 (with the largest number of recipients) as a representative LNP and simulated the clinical practice. Through designing a series of time points and three doses correlated with the PEG amount contained in three approved LNP-based drugs, we demonstrated that generation and changes of anti-PEG IgM and IgG were time- and dose-dependent. Unexpectedly, our data revealed that unlike other PEG derivatives belonging to thymus-independent antigens (TI-Ag), PEGylated LNP not only induced isotype switch and production of anti-PEG IgG, but caused immune memory, leading to rapid enhancement and longer lasting time of both anti-PEG IgM and IgG upon repeated injection. Importantly, pharmacokinetic studies discovered that initial injection of PEGylated LNP accelerated the blood clearance of subsequently injected LNP. These findings will refresh our understandings on PEGylated LNP and possible other PEG derivatives, and may lead to optimization of both premarket guidelines and clinical protocols of PEGylated LNP-delivered therapeutics.


Subject(s)
COVID-19 , Drug Hypersensitivity
7.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202211.0448.v1

ABSTRACT

Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the con-comitant release of granule contents that damage surrounding tissues into sharp focus. Neutro-phil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to cellular receptors and assist in the spread of infection. Blood and tissue fluids normally also contain liver-derived protease inhibitors that balance the activity of proteases. In-terestingly, neutrophils themselves also express the protease inhibitor alpha-1-antitrypsin (AAT), the product of the SERPINA-1 gene, and store it in neutrophil cytoplasmic granules. The absence of AAT or mutations in the SERPINA-1 gene promote lung remodeling and fibrosis in diseases such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and increase the risk of allergic responses. Recent observations point to the fact that re-duced activity of AAT presents a major susceptibility factor for severe COVID-19. Here, we focus attention on the mechanism of neutrophil elastase (NE) in NET release and its inhibition by AAT as an additional factor that may determine the severity of COVID-19


Subject(s)
Respiratory Distress Syndrome , COVID-19 , Fibrosis , Drug Hypersensitivity , Pulmonary Disease, Chronic Obstructive
8.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.11.24.22282707

ABSTRACT

Infectious agents contribute significantly to the global burden of diseases, through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genome-wide association studies in 9,611 participants from UK Biobank, we identified NFKB1 as a locus associated with quantitative antibody responses to multiple pathogens including those from the herpes, retro- and polyoma-virus families. An insertion-deletion variant thought to affect NFKB1 expression (rs28362491), was mapped as the likely causal variant. This variant has persisted throughout hominid evolution and could play a key role in regulation of the immune response. Using 121 infection and inflammation related traits in 487,297 UK Biobank participants, we show that the deletion allele was associated with an increased risk of infection from diverse pathogens but had a protective effect against allergic disease. We propose that altered expression of NFKB1 , as a result of the deletion, modulates haematopoietic pathways, and likely impacts cell survival, antibody production, and inflammation. Taken together, we show that disruptions to the tightly regulated immune processes may tip the balance between exacerbated immune responses and allergy, or increased risk of infection and impaired resolution of inflammation.


Subject(s)
Acute Disease , Drug Hypersensitivity , Virus Diseases , Inflammation
9.
authorea preprints; 2022.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.166853117.76921909.v1

ABSTRACT

Over six million individuals have died as a result of the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes Covid-19. The first COVID-19 vaccines were introduced to the public in 2020 through emergency authorizations. This study aims to uncover the fears and misconceptions behind the hesitation or refusal of taking the COVID-19 vaccine in Syria. Methods: Through a nationwide cross-sectional study, a convenience sample of 10006 participants who were at least 18 years old and living in Syria participated in a validated questionnaire during the period between January and May 2022 Results: The majority of recruited individuals were female (n= 6048; 60.4%) from the (18-24) age group (n= 5908; 59%). We recorded 5811 (58%) participants who still have fears and anxieties about the COVID-19 vaccine. The main concerns about vaccines were the rapid development of vaccines (41.4%), fears of blood clots (37.9%), the fears of common side effects (35.2%), and allergic reactions (26.5%). Conclusion: The COVID-19 vaccine is considered the most promising measure for controlling the spread of infection. The success of this policy will depend on the rate of global acceptance of the vaccine. High variability in vaccine acceptance and high vaccine hesitancy can affect the efforts to terminate the COVID-19 pandemic. Addressing the barriers associated with the acceptance of COVID-19 vaccination will be the cornerstone to achieving maximum vaccination coverage. The most common reasons behind refusing the vaccine in Syria were fear of side effects, followed by fears, general concerns, manufacturing-related reasons, and conspiracy belief


Subject(s)
Coronavirus Infections , COVID-19 , Anxiety Disorders , Drug Hypersensitivity
10.
authorea preprints; 2022.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.166853115.57337407.v1

ABSTRACT

Background: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation remains controversial. We therefore systematically investigated the genetic causal correlations of various ADs with COVID-19 infection/severity. Methods: : We systematically performed a two-sample, bidirectional Mendelian randomization (MR) study of five ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also validated the significant causal correlations and further elucidated underlying molecular mechanisms. Results: : The most suitable MR method, for the first time, revealed significant causal effects of COVID-19 infection/severity on an increased asthma prevalence (OR>4.21), which obtained further validations. In contrast, asthma consistently demonstrated causally protective effects on critically ill and hospitalized COVID-19 cases upon adopting multiple MR methods (OR, 0.96–0.99). Our MR analyses also observed potential causal correlations of COVID-19 severity with atopic dermatitis, shrimp and peach allergy. Regarding underlying molecular mechanisms, we observed that COVID-19 phenotypes, especially those critically ill cases, were causally correlated to hematological traits and count data of immune-related cells. In contrast, ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting ACE2 protein expression. Conclusions: : Our MR analyses suggest a bidirectional causal effect between COVID-19 phenotypes and ADs, especially asthma. The potential underlying molecular mechanisms of the causal effects may be beneficial in developing effective therapeutic strategies for allergy patients with COVID-19 infection and call for more attention to their physical characteristics upon showing long-term COVID-19 symptoms.


Subject(s)
COVID-19 , Drug Hypersensitivity , Asthma , Dermatitis, Atopic
11.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2211719.v1

ABSTRACT

Background Public health depends on both medical treatment development and the public’s willingness to take such treatment. To determine whether having experienced delayed localized hypersensitivity reactions to COVID-19 vaccines, i.e., “COVID arm” symptoms affect confidence in the safety of vaccination, willingness to take COVID-19 vaccines, and the acknowledgement of the importance of vaccination, and also confidence in science. Methods We implemented a panel survey on internet in February 2021 and March 2022 in Japan, before and after COVID-19 vaccines were administered to the public in Japan, and we used “COVID arm” symptoms, which are independent of one’s prior confidence in vaccination, as our instrument. Out of the non-probability sample of 15,000 respondents in the first wave in February 2021, 9,668 responded to the second wave conducted in March 2022. We used “COVID arm” symptoms as a natural experiment conditional on the background characteristics of the respondents. Main outcomes are whether having experienced “COVID arm” symptoms affected 1) confidence in the safety of vaccination; 2) willingness to take the next dose of COVID-19 vaccines, 3) acknowledgment of the importance of vaccination, and 4) confidence in science. Measures are marginal means of the probability of a positive reaction to each question. Results Experiencing “COVID arm” symptoms significantly lowered confidence in the safety of vaccination by 3.4 percentage points and the probability of taking a second and third dose of COVID-19 vaccine by 1.2 and 3.4 percentage points, respectively. Adverse impacts were observed regardless of prior confidence in vaccination. Experiencing such symptoms affected neither the acknowledged importance of vaccination nor confidence in science. Conclusions Updates to beliefs about side effects affected confidence in the safety of vaccination. Acknowledgment of vaccination importance and general confidence in science are likely to have factored in the uncertainty and to be tolerant of updates to one’s beliefs about side effects. Belief updates of specific treatments had asymmetric impacts on the treatment and medicine in general. Trial registration The design of the survey was preregistered with the American Economic Association’s RCT Registry [1].


Subject(s)
COVID-19 , Drug Hypersensitivity
12.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.21.22281356

ABSTRACT

Objective: The growing number of Coronavirus Disease-2019 (COVID-19) survivors who are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS) represent a worldwide public health challenge. Yet, the novelty of this condition and the resulting limited data on underlying pathomechanisms so far hampered the advancement of effective therapies. Using electronic health records (EHR) data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models. Methods: In our cohort of 63,675 COVID-19 positive patients seen at Michigan Medicine, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design comparing PASC cases with 17,205 matched controls and performed phenome-wide association studies (PheWASs) to characterize enriched phenotypes of the post-COVID-19 period and potential PASC pre-disposing phenotypes of the pre-, and acute-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, cases were significantly enriched for known PASC symptoms (e.g., shortness of breath, malaise/fatigue, and cardiac dysrhythmias) but also many musculoskeletal, infectious, and digestive disorders. We found seven phenotypes in the pre-COVID-19 period (irritable bowel syndrome, concussion, nausea/vomiting, shortness of breath, respiratory abnormalities, allergic reaction to food, and circulatory disease) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological, digestive, and mental health phenotypes) that were significantly associated with PASC. The derived pre-COVID-19 PheRS and acute-COVID-19 PheRS had low accuracy to differentiate cases from controls; however, they stratified risk well, e.g., a combination of the two PheRSs identified a quarter of the COVID-19 positive cohort at a 3.5-fold increased risk for PASC compared to the bottom 50% of their distributions. Conclusions: Our agnostic screen of time stamped EHR data uncovered a plethora of PASC-associated diagnoses across many categories and highlighted a complex arrangement of presenting and likely pre-disposing features -- the latter with a potential for risk stratification approaches. Yet, considerably more work will need to be done to better characterize PASC and its subtypes, especially long-term consequences, and to consider more comprehensive risk models.


Subject(s)
Postoperative Nausea and Vomiting , Coronavirus Infections , COVID-19 , Drug Hypersensitivity , Respiratory System Abnormalities , Dyspnea , Severe Acute Respiratory Syndrome , Irritable Bowel Syndrome , Fatigue , Arrhythmias, Cardiac
13.
Int J Mycobacteriol ; 11(3): 309-317, 2022.
Article in English | MEDLINE | ID: covidwho-2055697

ABSTRACT

Background: The World Health Organization Global Tuberculosis Report 2021 defines tuberculosis as the second infectious disease that causes sickness and death after COVID 19 and ranks it as the 13th among the global causes of death. However, the prevalence of the patients developing a hypersensitivity reaction against antituberculosis treatment is yet unknown. This study aimed to investigate the prevalence of drug allergy against antituberculosis treatment and the management of such a problem. Methods: This is a case--control study. All patients hospitalized in the tuberculosis inpatient service between February 01, 2015 and May 01, 2021 due to hypersensitivity reaction or who developed hypersensitivity during hospitalization were included in the case group. Patients who received inpatient treatment between the same dates and did not develop any drug allergy were included in the control group. The demographic characteristics of the patients, the tuberculosis diagnostic indicator, the type of hypersensitivity reaction that developed, the duration of the manifestation of the reaction and its treatment were evaluated for the purpose of the study. Results: A total of 2677 patients were hospitalized in the tuberculosis inpatient service between the specified dates. Two hundred and ten patients were consulted for drug hypersensitivity reactions in the Allergy Clinic. The prevalence of drug allergy in inpatients was calculated as 7.8%. One hundred and forty-eight patients examined by the authors were included in the study. Seventy-nine of the 148 patients (53.4%) who developed a hypersensitivity reaction were male, the mean age of these patients was 47.20 ± 18.95 years, 89.2% (n = 132) were citizens of the Republic of Turkey, 7.4% (n = 11) of the patients had received tuberculosis treatment before, 16.9% (25) had developed antituberculosis drug resistance and the bacteriological diagnosis was present in 79.7% (118) of the patients. Chi-square test results applied in the allergy group revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P < 0.001), Turkish citizen patients (P = 0.004), in new cases (P = 0.017), in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The results of the logistic regression analysis performed also revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P = 0.006), Turkish citizen patients (P = 0.023), in new cases (P = 0.017) and in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The success of the treatment was higher in the group that developed a hypersensitivity reaction compared to the control group. About 63.5% (94) of the patients examined developed Type I hypersensitivity reactions, whereas 36.7% (53) of the patients examined developed Type IV hypersensitivity reactions. Type I and Type IV reactions were observed simultaneously in a single patient. Considering the prevalence of developing a hypersensitivity reaction, pyrazinamide was determined as the drug inducing the hypersensitivity reaction in 25 (48.1%) patients. This figure was 15 patients (28.2%) for rifampicin, nine patients (17.3%) for isoniazid, and five patients (9.6%) for ethambutol. As a result, even patients who developed Type I or Type IV reactions were able to complete their antituberculous drug regimens with successful desensitization. Conclusion: The risk of developing an allergic reaction in patients who are administered on antituberculosis treatment is common, particularly in the first 2 months of treatment. However, we believe that the compliance of the patients to the antituberculosis treatment has been improved at the end of appropriate management of hypersensitivity reactions and the treatment results in success.


Subject(s)
COVID-19 , Drug Hypersensitivity , Tuberculosis , Humans , Male , Female , Adult , Middle Aged , Aged , Antitubercular Agents/adverse effects , Isoniazid/therapeutic use , Ethambutol/therapeutic use , Pyrazinamide/therapeutic use , Rifampin/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/etiology , Drug Hypersensitivity/drug therapy
14.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.03.22280227

ABSTRACT

The polyethylene-glycol (PEG)-containing Covid-19 vaccines can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet proven in humans. The 191 blood donors in this study included 10 women and 5 men who displayed HSRs to Comirnaty or Spikevax Covid-19 vaccines with 3 anaphylaxis. 118 donors had pre-vaccination anti-PEG IgG/IgM values as measured by ELISA, of which >98% were over background regardless of age, indicating the presence of these Abs in almost everyone. Their values varied over 2-3 orders of magnitude and displayed strong left-skewed distribution with 3-4% of subjects having >15-30-fold higher values than the respective median. First, or booster injections with both vaccines led to significant rises of anti-PEG IgG/IgM with >10-fold rises in about ~10% of Comirnaty, and all Spikevax recipients, measured at different times after the injections. The anti-PEG Ab levels measured within 4-months after the HSRs were significantly higher than those in nonreactors. Serial testing of plasma (n=361 tests) showed the SARS-CoV-2 neutralization IgG to vary over a broad range, with a trend for biphasic dose dependence on anti-PEG Abs. The highest prevalence of anti-PEG Ab positivity in human blood reported to date represents new information which can most easily be rationalized by daily exposure to common PEG-containing medications and/or household items. The significantly higher, HSR-non-coincidental blood level of anti-PEG Abs in hypersensitivity reactor vs. non-reactors, taken together with relevant clinical and experimental data in the literature, suggest that anti-PEG Ab supercarrier people might be at increased risk for HSRs to PEG-containing vaccines, which themselves can induce these Abs via bystander immunogenicity. Our data also raise the possibility that anti-PEG Abs might also contribute to the reduction of these vaccines' virus neutralization efficacy. Thus, screening for anti-PEG Ab supercarriers may identify people at risk for HSRs or reduced vaccine effectiveness.


Subject(s)
COVID-19 , Drug Hypersensitivity
15.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2120324.v1

ABSTRACT

The sudden onset of Covid-19 pandemic has led to the implementation of various health-care measures, among which the facemask has become the primary line of defense. Several masks available in the market are single-use that would choke the environment through plastic pollution, or too expensive for the commoner to afford. As the pandemic affected population of all races, religions and communities across the globe, there was a need to design a low-cost mask that could be washed and reused multiple times without loss in barrier properties. The present work relates to the design of a facemask that incorporates a waste derived warp knit polyethylene terephthalate (PET) permeate spacer extricated from used reverse osmosis (RO) and other membrane modules. A non-woven polypropylene (PP) layer was incorporated immediately after the PET layer to provide high hydrophobicity and increase the threshold pressure for the respiratory droplets to penetrate. These two active layers were sandwiched between two tightly woven cotton layers as the first and fourth layers. The cotton fabric of the developed mask provides comfort, good appearance, biodegradable nature and tightly woven that reject larger particulate matter including dust. The unique PET layer has high mechanical strength and 3D shape holding capability that extended from the nose bridge to the chin, leaving an air gap between the mouth and the inner layer of the facemask, enabling smooth facial movement, hindrance-free speaking and prevents spectacle fogging. The PP layer is also known to exhibit electrostatic repulsion towards pathogens present in the air and prevents the chances of infections. Compared to commercial N95 mask, the developed mask exhibits high breathability, reusable up to 30 washes and is produced at an affordable cost of Rs.17 (0.22 USD) including labor charges and sold at 100% profit margin @ Rs.35 (0.45 USD) per unit. The developed mask has high bacterial filtration efficiency and prevents respiratory droplets containing infection causing organisms, dust allergies, and those arising from environmental pollution. Moreover, the mask was certified by neutral testing agencies and sold to a population of more than 6 lakhs thus playing a major role in mitigation of Covid-19.


Subject(s)
COVID-19 , Drug Hypersensitivity
16.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.20.22279903

ABSTRACT

BACKGROUND Over 20% of cases and 0.4% of deaths from Covid-19 occur in children. Following demonstration of safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial enrolled adolescents. METHODS Safety, immunogenicity, and efficacy of NVX-CoV2373 were evaluated in adolescents aged 12 to <18 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States. Participants were randomized 2:1 to two doses of NVX-CoV2373 or placebo 21 days apart, and followed for a median of 2 months after second vaccination. Primary end points were serologic non-inferiority of neutralizing antibody (NA) responses compared with young adults (18 to <26 years) in PREVENT-19, protective efficacy against laboratory-confirmed Covid-19, and assessment of reactogenicity/safety. RESULTS Among 2,247 participants randomized between April-June 2021, 1,491 were allocated to NVX-CoV2373 and 756 to placebo. Post-vaccination, the ratio of NA geometric mean titers in adolescents compared to young adults was 1.5 (95% confidence interval [CI] 1.3 to 1.7). Twenty Covid-19 cases (all mild) occurred: 6 among NVX-CoV2373 and 14 among placebo recipients (vaccine efficacy [VE]: 79.5%, 95% CI, 46.8 to 92.1). All sequenced viral genomes (11/20) were identified as Delta variant (Delta variant VE: 82.0% [95% CI: 32.4 to 95.2]). Reactogenicity was largely mild-to-moderate, transient, and more frequent in NVX-CoV2373 recipients and after the second dose. Serious adverse events were rare and evenly distributed between treatments. CONCLUSIONS NVX-CoV2373 was safe, immunogenic, and efficacious in the prevention of Covid-19 and those cases caused by the Delta variant in adolescents. (Funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; PREVENT-19 ClinicalTrials.gov number, NCT04611802).


Subject(s)
Communicable Diseases , COVID-19 , Drug Hypersensitivity
17.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.30.22279383

ABSTRACT

Background. Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. Methods. Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection=56.06, standard deviation [SD]=7.37, 918 (93.4%) male, 813 (82.7%) European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category, that included hospitalization and other adverse outcomes; 306 (31.1%) reported at least one post-acute COVID-19 symptom at the 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. Findings. In responders with European ancestry, the asthma PRS was associated with severe COVID-19 category (odds ratio [OR]=1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology ({beta}=.09, p=.01), independently of respiratory disease diagnosis. The allergic disease PRS similarly associated with severe COVID-19 category (OR=1.97, [1.26-3.07]). The PRS for COVID-19 hospitalization was associated with the risk of severe COVID-19 category (OR=1.35, [1.01-1.82]), but this association was smaller than for the asthma PRS. PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. Interpretation. Taken together, the results indicate that recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population. Funding. National Institute for Occupational Safety and Health, CDC.


Subject(s)
Diabetes Mellitus, Type 2 , COVID-19 , Drug Hypersensitivity , Asthma , Respiratory Tract Diseases , Coronary Artery Disease
18.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.08.19.504551

ABSTRACT

Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.


Subject(s)
Agnosia , Influenza, Human , Acute Disease , COVID-19 , Pain , Drug Hypersensitivity , Severe Acute Respiratory Syndrome , Sensation Disorders , Amyloid Neuropathies, Familial
19.
Allergy ; 77(12): 3527-3537, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1968057

ABSTRACT

Hypersensitivity reactions to drugs are increasing worldwide. They display a large degree of variability in the immunological mechanisms involved, which impacts both disease severity and the optimal diagnostic procedure. Therefore, drug hypersensitivity diagnosis relies on both in vitro and in vivo assessments, although most of the methods are not well standardized. Moreover, several biomarkers can be used as valuable parameters for precision medicine that provide information on the endotypes, diagnosis, prognosis, and prediction of drug hypersensitivity development, as well on the identification of therapeutic targets and treatment efficacy monitoring. Furthermore, in the last 2 years, the SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) pandemic has had an important impact on health system, leading us to update approaches on how to manage hypersensitivity reactions to drugs used for its treatment and on COVID-19 (Coronavirus disease) vaccines used for its prevention. This article reviews recent advances in these 3 areas regarding drug hypersensitivity: in vitro tools for drug hypersensitivity diagnosis, recently identified biomarkers that could guide clinical decision making and management of hypersensitivity reactions to drugs and vaccines used for COVID-19.


Subject(s)
COVID-19 , Drug Hypersensitivity , Vaccines , Humans , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , COVID-19/prevention & control , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/therapy , Biomarkers
20.
Medicine (Baltimore) ; 101(30): e29571, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967936

ABSTRACT

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.


Subject(s)
Anaphylaxis , COVID-19 Vaccines , COVID-19 , Dermatitis, Atopic , Drug Hypersensitivity , Adult , Anaphylaxis/epidemiology , Anaphylaxis/etiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Dermatitis, Atopic/complications , Drug Hypersensitivity/complications , Humans , Incidence , RNA, Messenger
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