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1.
BMC Research Notes ; 14(401), 2021.
Article in English | CAB Abstracts | ID: covidwho-1841025

ABSTRACT

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals.

2.
Pediatric Allergy and Immunology ; 33(s27):58-60, 2022.
Article in English | CAB Abstracts | ID: covidwho-1840508

ABSTRACT

Allergic individuals at risk for hypersensitivity reactions to measles vaccine marketed for a long time are well established. On the other hand, risk factors for hypersensitivity reactions to the new mRNA COVID-19 vaccines currently include a history of allergy, allergy to excipient of the vaccine, or hypersensitivity reactions to the first dose of COVID-19 vaccine. In the last two cases, the recipient should be assessed by an allergist before vaccination to share a decision on the choice of vaccination. Studies on skin testing accuracy and desensitization protocols to the COVID-19 vaccines and the efficacy of potential alternatives in patients with confirmed hypersensitivity reactions to the first COVID-19 vaccine are necessary to improve the safety of COVID-19 vaccines.

3.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-336229

ABSTRACT

Background: We estimated vaccine effectiveness (VE) of mRNA vaccines among US Veterans during periods of Delta and Omicron variant dominance. Patients included in this study were largely 65 years or older (62,834, 55%), male (101,259, 88%), and non-Hispanic white (66,986, 58%). Methods: We used SARS-CoV-2 laboratory test results to conduct a matched test-negative case-control study to estimate VE of three and two doses of mRNA vaccines against infection (regardless of symptoms), and a matched case-control study to estimate VE against COVID-19related hospitalization and death. We estimated VE as (1- odds ratio) x 100%. Severity of disease was measured using hospital length of stay (LOS) and admission to an intensive care unit (ICU). Results: Against infection, booster doses had 7-times higher VE - 59% (95% confidence interval [CI], 57 to 61) - than 2-dose VE (7%;95% CI, 3 to 10) during the Omicron period. For the Delta period, estimated VE against infection was 90% (95% CI, 88 to 92) among boosted vaccinees, 64% higher than VE among 2-dose vaccinees [55% (95% CI, 51 to 58)]. Against hospitalization, booster dose VE was 87% (95% CI, 80 to 91) during Omicron and 95% (95% CI, 91 to 97) during Delta;the 2-dose VE was 44% (95% CI, 26 to 58) during Omicron and 75% (95% CI, 70 to 80) during Delta. Against death, estimated VE with a booster dose was 94% (95% CI, 85 to 98) during Omicron and 96% (95% CI, 88 to 99) during Delta, while the 2-dose VE was 75% (95% CI, 52 to 87) during Omicron and 93% (95% CI, 85 to 97) during Delta. During the Omicron period, average hospital LOS was 4 days shorter [3 days (95%CI, 3 to 4 days)] than during the Delta period. Conclusions: A mRNA vaccine booster is more effective against infection, hospitalization, and death than 2-dose vaccination among an older male population with comorbidities.

4.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-335889

ABSTRACT

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. Only limited data exists about the short- and long-term dynamics of humoral immune response. We present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1697 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus. Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group 35-70 days after vaccination. The decrease of IgG levels is gradual, with lower overall values in the infection naïve cohort even 7-8 months after vaccination, compared to the previously infected cohort. Administration of a booster dose yielded higher average IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.

5.
Sri Lankan Journal of Infectious Diseases ; 12(1), 2022.
Article in English | CAB Abstracts | ID: covidwho-1835014

ABSTRACT

Since the emergence of SARS CoV-2 in 2019, the global population has had to implement major lifestyle changes in order to circumvent death and severe morbidity caused in the wake of the virus, as well as endure the consequences on the economy and social wellbeing. However, restrictions posed by the pandemic have not deterred scientists from engineering a solution to this in the form of vaccines against SARS CoV-2. Although their efficacy has been proven, recent reports have claimed that these vaccines may not be as safe as they are promoted to be, and that they may cause adverse effects that outweigh their benefits. This article offers an objective perspective of the unfavourable side effects of five widely used vaccine candidates for SARS CoV-2, BNT162b2, mRNA 1273, ChAdOx1 nCoV-19, Sputnik V and BBIBP CorV, to highlight that the panic associated with vaccination is unjustified in light of recent developments.

6.
Pharmaceuticals ; 15(2), 2022.
Article in English | CAB Abstracts | ID: covidwho-1834862

ABSTRACT

Cancer is a severe health condition and considered one of the major healthcare issues and is in need of innovative strategy for a cure. The current study aimed to investigate the chemical profile of Trigonella hamosa L. and a potential molecular approach to explain its regulation in cancer progression through an inflammatory mediator (COX-2) in A549 non-small lung cancer cell lines via in silico, mechanistic and molecular aspects. T. hamosa was extracted and then subjected to a CCK-8 cell viability assay in different cancer cell lines including MDA-MB-231, A549 and HCT-116. Total extract was subjected to several chromatographic techniques to yield orientin (OT);the structure was elucidated by inspection of NMR spectroscopic data. To achieve anticancer effects of OT, a cell viability assay using a CCK-8 kit, immunoprecipitation by Western blot, cell migration using a wound healing assay, cell invasion using a Matrigel-Transwell assay, apoptosis by AO/EB dual staining, flow cytometric analysis and DAPI staining, a silenced COX-2 model to determine PGE-2 production and real-time PCR and Western blot of BCL-2, CYP-1A1, iNOS and COX-2 markers were carried out. The results demonstrated that OT decreased the cell proliferation and controlled cell migration and invasive properties. OT destabilized the COX-2 mRNA and downregulated its expression in A549 cell lines. Virtual binding showed interaction (binding energy -10.43) between OT and COX-2 protein compared to the selective COX-2 inhibitor celecoxib (CLX) (binding energy -9.4). The OT-CLX combination showed a superior anticancer effect. The synergistic effect of OT-CLX combination was noticed in controlling the migration and invasion of A549 cell lines. OT-CLX downregulated the expression of BCL-2, iNOS and COX-2 and activated the proapoptotic gene CYP-1A1. OT mitigated the COX-2 expression via upregulation of miR-26b and miR-146a. Interestingly, COX-2-silenced transfected A549 cells exhibited reduced expression of miR-26b and miR-146a. The findings confirmed the direct interaction of OT with COX-2 protein. PGE-2 expression was quantified in both naive and COX-2-silenced A549 cells. OT downregulated the release of PGE-2 in both tested conditions. These results confirmed the regulatory effect of OT on A549 cell growth in a COX-2-dependent manner. OT activated apoptosis via activation of CYP-1A1 expression in an independent manner. These results revealed that the OT-CLX combination could serve as a potential synergistic treatment for effective inflammatory-mediated anticancer strategies.

7.
Science ; 376(6592):446-446, 2022.
Article in English | Academic Search Complete | ID: covidwho-1832326

ABSTRACT

The article presents the discussion on third messenger RNA (mRNA) vaccine for COVID-19. Topics include Pfizer-BioNTech and Moderna vaccines containing mRNA coding for the SARSCoV-2 spike protein;enzymes from alphaviruses repeatedly copying the genetic strand inside a cell;and replacement of the natural RNA building blocking the uridine with pseudouridine.

8.
Pediatric Dermatology ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-1832221

ABSTRACT

A 12‐year‐old boy presented with a 2‐week history of persistent pruritic edematous plaques one day after he received the first dose of the BNT162b2 COVID‐19 mRNA vaccine. A skin biopsy showed urticarial dermatitis with tissue eosinophilia consistent with a diagnosis of vaccine‐associated eosinophilic cellulitis, with polyethylene glycol as a potential trigger. [ FROM AUTHOR] Copyright of Pediatric Dermatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

9.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334871

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.

10.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334813

ABSTRACT

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART- naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans, yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced “Trojan Horse” in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage “Trojan Horse”, myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

11.
EClinicalMedicine ; 45(29), 2022.
Article in English | CAB Abstracts | ID: covidwho-1828409

ABSTRACT

Background: mRNA COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have been shown to be efficacious but have not been compared in head-to-head clinical trials.

12.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822468

ABSTRACT

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical examination and ultrasound imaging confirmed the patient’s observation. The effect was sustained, and further reduction of the nodules occurred after the third vaccine dose. One of the reduced nodules was removed, histologically examined, and its histopathology was compared to that of another such nodule removed and examined earlier. Distinct differences were observed between the two histopathologies, with the most notable the unexpected finding of the absence of infiltrating lymphocytes in the reducer nodule’s melanoma tissue. Based on this observation, the possible immunological mechanism(s) leading to the vaccine’s effect are speculated. More possible is the vaccine’s antitumor and apoptotic activity via stimulation of the Tol Like Receptors 3, 7, and 8, and (downstream) the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of the non-lymphocytic immune effector cells.

13.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822466

ABSTRACT

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases;however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non-or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters.

14.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822459

ABSTRACT

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.

15.
Viruses ; 14(5), 2022.
Article in English | EMBASE | ID: covidwho-1822447

ABSTRACT

Background: This study aimed to investigate the early and longitudinal humoral response in Healthcare Workers (HCWs) after two doses of the BNT162b2 vaccine and to assess the association between metabolic and anthropometric parameters and the humoral response after vaccination. Methods: The study included 243 fully vaccinated HCWs: 25.50% previously infected with SARS-CoV-2 (with prior history of COVID-19—PH) and 74.40%—uninfected, seronegative before the first vaccination (with no prior history of COVID-19—NPH). IgG antibodies were measured, and sera were collected: prior to the vaccination, 21 days after the first dose, and 14 days and 8 months after the second dose. Results: 21 days after the first dose, 90.95% of individuals were seropositive;14 days after the second dose, persistent immunity was observed in 99.18% HCWs, 8 months after complete vaccination—in 61.73%. Statistical analysis revealed that HCWs with PH had a greater chance of maintaining a humoral response beyond eight months after vaccination. Increased muscle mass, decreased fat mass, and younger age may positively affect long-term immunity. Smokers have a reduced chance of developing immunity compared to non-smokers. Conclusions: Fully vaccinated HCWs with PH are more likely to be seropositive than fully inoculated volunteers with NPH.

16.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822362

ABSTRACT

The antibody and T cell responses after SARS-CoV-2 vaccination have not been formally compared between kidney and liver transplant recipients. Using a multiplex assay, we measured IgG levels against 4 epitopes of SARS-CoV-2 spike protein and nucleocapsid (NC) antigen, SARS-CoV-2 variants, and common coronaviruses in serial blood samples from 52 kidney and 50 liver transplant recipients undergoing mRNA SARS-CoV-2 vaccination. We quantified IFN-γ/IL-2 T cells reactive against SARS-CoV-2 spike protein by FluoroSpot. We used multivariable generalized linear models to adjust for the differences in immunosuppression between groups. In liver transplant recipients, IgG levels against every SARS-CoV-2 spike epitope increased significantly more than in kidney transplant recipients (MFI: 19,617 vs 6,056;P<0.001), a difference that remained significant after adjustments. Vaccine did not affect IgG levels against NC nor common coronaviruses. Elicited antibodies recognized all variants tested but at significantly lower strength than the original Wuhan strain. Anti-spike IFN-γ-producing T cells increased significantly more in liver than in kidney transplant recipients (IFN-γ-producing T cells 28 vs 11 spots/5x105 cells), but this difference lost statistical significance after adjustments. SARS-CoV-2 vaccine elicits a stronger antibody response in liver than in kidney transplant recipients, a phenomenon that is not entirely explained by the different immunosuppression.

17.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821935

ABSTRACT

SARS-COV-2, or COVID-19, is a respiratory virus infecting over 86 million people worldwide. In addition to respiratory infections, SARS-COV-2 has been shown to include cardiovascular (CV) complications, including myocarditis and acute coronary syndrome. Risk of severe complications from SARS-COV-2 in individuals with existing CV and metabolic disease has been shown to be increased. Evidence indicates SARS-COV-2 enters tissues via the angiotensin-converting enzyme 2 (ACE2) receptor and that the virus is primed and activated by transmembrane protease, serine 2 (TMPRSS2). The goal of this study was to determine ACE2 and TMPRSS2 mRNA levels in pre-clinical swine models of heart failure (HF). We hypothesized sex, pressure-overload, and comorbidities would increase ACE2 and TMPRSS2 mRNA levels. A retrospective analysis was conducted in previously completed studies in our lab including: 1) Female, intact Ossabaw swine that were either lean control or western diet-fed aortic-banded (N=4-5/group);2) Female Yucatan mini-swine subject to ovariectomy and/or aortic banding (N=5-8/group);and 3) Sedentary and exercise trained male, intact Yucatan mini-swine that were aortic banded. ACE2 and TMPRSS2 mRNA levels were evaluated in the left ventricle (LV), right ventricle (RV), and coronary vasculature using qRT-PCR. Linear regression analysis was used to determine differences between the following variables: pig species, sex hormones, aortic banding, comorbidities, exercise training, and tissue. Data was log-transformed to meet linear regression assumptions. ACE2 and TMPRSS2 mRNA levels were significantly influenced by sex, comorbidity, and tissue type. TMPRSS2 mRNA levels were also influenced by species and disease status. Specifically, ACE2 mRNA levels decreased 57.1% in the LV and increased 169.9% in the RV of males compared to coronary vessels in intact females. TMPRSS2 mRNA levels increased in the LV and RV of males (1,218.6% and 5,479.8%, respectively) compared to coronary vessels in intact females. ACE2 and TMPRSS2 mRNA levels increased 344% and 453.4%, respectively, in the LV of Ossabaw swine fed a Western Diet compared to coronary vessels from Yucatan and Ossabaw swine without comorbidities. Species differences indicated TMPRSS2 mRNA levels increased 449.2% in the RV and 498.6% in the LV in Yucatan mini-swine compared to coronary vessels in Ossabaw swine. A 107.3% increase in TMPRSS2 mRNA level was observed in male swine without HF compared to female intact swine with HF highlighting the importance of sex and disease state. Exercise training did not impact ACE2 or TMPRSS2 mRNA levels irrespective of tissue. In conclusion, these results suggest differences in RV, LV and coronary mRNA levels of ACE2 and TMPRSS2 are dependent upon sex and comorbidities. TMPRSS2 levels are additionally influenced by pig species and pressureoverload. These results provide insight into how ACE2 and TMPRSS2 mRNA levels may influence the cardiovascular involvement of SARS-COV-2 infection in an experimental setting of pre-clinical HF incorporating different swine species, sex, and comorbidities.

18.
Journal of Excipients and Food Chemicals ; 13(1):4-17, 2022.
Article in English | EMBASE | ID: covidwho-1820630

ABSTRACT

Excipients are critically important in converting active pharmaceutical ingredients (API) into drug products that have optimal stability, bioavailability, manufacturability, duration of action, and therapeutic benefits. They will play even greater roles in the future to enable drug targeting, delivery of biotech products and vaccines, gene therapy, continuous manufacturing, 3D printing, and so forth. This commentary describes the author’s experience in teaching a graduate course on excipients at St. John’s University to train students on optimal selection and appropriate use of excipients in formulating dosage forms and development of drug delivery systems. The course is offered in 15 two-hour sessions over a semester, and the course materials are divided into 13 modules on chemistry of different classes of polymeric and non-polymeric excipients and their application in dosage form development, including the use as solubilizing agents, lyophilizing agents, cryoprotectants, buffers, biodegradable materials, and carriers for amorphous solid dispersions and 3D printing. The development of coprocessed excipients, the need for new excipients, and the regulatory aspects of excipients are also covered. The course includes presentations by guest speakers from the industry, and the students also watch virtual presentations from experts that are publicly available from the internet. It is a popular course at St. John’s University taken by all graduate students in the pharmaceutics program. It is recommended that such courses are introduced in other pharmacy schools and academic institutions. The course may be adapted to meet specific needs of different academic programs. Professional associations, such as AAPS and CRS, industry groups like IPEC, and the pharmaceutical industry may be able to help in introducing such courses by providing lecture materials and guest lecturers.

19.
Cardiogenetics ; 12(2):133-141, 2022.
Article in English | EMBASE | ID: covidwho-1818054

ABSTRACT

Eosinophilic pancarditis (EP) is a rare, often unrecognized condition caused by endomyocardial infiltration of eosinophil granulocytes (referred as eosinophilic myocarditis, EM) associated with pericardial involvement. EM has a variable clinical presentation, ranging from asymptomatic cases to acute cardiogenic shock requiring mechanical circulatory support (MCS) or chronic restrictive cardiomyopathy at high risk of progression to dilated cardiomyopathy (DCM). EP is associated with high in‐hospital mortality, particularly when associated to endomyocardial thrombosis, coronary arteries vasculitis or severe left ventricular systolic dysfunction. To date, there is a lack of consensus about the optimal diagnostic algorithm and clinical management of patients with biopsy‐proven EP. The differential diagnosis includes hypersensitivity myocarditis, eosinophil granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome, parasitic infections, pregnancy‐related hypereosinophilia, malignancies, drug overdose (particularly clozapine) and Omenn syndrome (OMIM 603554). To our knowledge, we report the first case of pancarditis associated to eosinophilic granulomatosis with polyangiitis (EGPA) with negative anti‐neutrophil cytoplasmic antibodies (ANCA). Treatment with steroids and azathioprine was promptly started. Six months later, the patient developed a relapse: treatment with subcutaneous mepolizumab was added on the top of standard therapy, with prompt disease activity remission. This case highlights the role of a multimodality approach for the diagnosis of cardiac involvement associated to systemic immune disorders.

20.
Allergy, Asthma and Clinical Immunology ; 18(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1817260

ABSTRACT

Background: Mast cells are tissue-resident sentinels that regulate responses to pathogens and allergens. They are critical for hypersensitivity reactions and typically activated in Th2 cytokine-rich environments during allergic disease. Mast cells respond to viruses by producing chemokines and type I and III interferons (IFNs). Clinical studies have investigated Th2 cytokine inhibitors, including IL-5 inhibitors, in asthma therapy1- 3. However, the influence of IL-5 inhibition on mast cell responses to virus infection remains unclear. The effects of IL-5 or IL-5 inhibition on mast cell antiviral responses may be important in virus-associated exacerbation of asthma. Methods: Human cord-blood-derived mast cells from anonymized donors (n = 14;12 donors) were isolated and pre-treated in culture medium with or without 10 ng/mL IL-5 for 48 hours. Cells were infected with OC43 coronavirus at 1.0 MOI, treated with poly(I:C), or left in culture medium (mock) for 24 hours. qPCR and Luminex analysis were performed to assess mRNA and protein levels for type I and III IFNs. Statistical analysis was performed using mixed-effects analysis with Sidak's multiple comparisons test. Results: Coronavirus infection or poly(I:C) treatment of mast cells resulted in significantly higher levels of IFNA2, IFNB1, and IFNL1 mRNA compared to respective mock treatments (p < 0.01-0.0001). Luminex analysis revealed that IFNα2 production was increased in IL-5-pretreated and non-pre-treated cells following poly(I:C) stimulation and following coronavirus infection of IL-5-pre-treated cells compared to controls (p < 0.001-0.0001). Interestingly, the enhancement of mRNA and protein expression following coronavirus infection or poly(I:C) treatment was significantly greater in IL-5-pre-treated compared to non-pre-treated mast cells for all targets (p < 0.05-0.001). Conclusions: IL-5-pre-treatment enhances the expression of type I and III IFN mRNAs by mast cells in response to coronavirus or poly(I:C), suggesting IL-5 may have an important role in mast cell antiviral responses. The mechanism by which IL-5 enhances mast cell IFN expression will be investigated further.

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