The Association of COVID-19 Severity with Laboratory Parameters, Radiologic Findings, Maternal and Neonatal Outcomes in Pregnant Women: A Multicenter Study in Indonesia

Objectives: Severe acute respiratory syndrome-coronavirus 2/COVID-19 infection is still a global concern, with pregnant women are considered as vulnerable population. Until now, the characteristics of pregnant women in Indonesia who are infected with COVID-19, as well as pregnancy and neonatal outcomes, are still unknown. This study aims to obtain national data, which are expected to be useful for the prevention and management of COVID-19 in pregnant women in Indonesia. Method(s): There were 1,427 patients recruited in this retrospective multicenter study. This study involved 11 hospitals in 10 provinces in Indonesia and was carried out using secondary patient data from April 2020 to July 2021. COVID-19 severity was differentiated into asymptomatic-to-mild symptoms and moderate-to-severe symptoms. The collected data include maternal characteristics, laboratory examinations, imaging, pregnancy outcomes, and neonatal outcomes. Result(s): Leukocyte, platelets, basophil, neutrophils segment, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), urea, and creatinine were found to be significantly associated with severity differences (p < 0.05). Moderate-severe symptoms of COVID-19 also shown to have suggestive pneumonia findings on chest X-ray findings. Patients with asymptomatic-to-mild symptoms had significantly (p < 0.001) higher recovery rate, shorter hospital stay, less intensive care unit (ICU) admission, and had more vaginal delivery. Neonates from mother with mild symptoms also had significantly (p < 0.001) higher survival rate, higher birth weight, and higher APGAR score. Conclusion(s): Several laboratory and radiology components, as well as maternal and neonatal outcomes are related to the severity of COVID-19 in pregnant women in Indonesia.Copyright © The Author(s). 2023.

The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

Asthma in the elderly and COVID-19: results of the 90-day post-hospital follow-up.

Background. After the first wave of the new SARS-CoV-2 coronavirus infection, the researchers focused on identifying potential short-and long-term complications of COVID-19, especially in high-risk patients, after prolonged hospitalization and intensive care. Objective. To study the outcomes, adverse effects of severe COVID-19 and their predictors 90 days after hospital discharge in elderly patients with asthma. Material and methods. The study included elderly patients (101 subjects, 42 males and 59 females;median age 74 (67;79) years) with asthma, discharged from the hospital after treatment of severe COVID-19. They were followed up for 90 days after discharge. In the hospital, COVID-19 was confirmed by laboratory tests (polymerase chain reaction method) and/or clinically and radiologically. All patients had a documented history of asthma according to GINA 2020 criteria. Results and discussion. During the 90-day post-hospital follow-up, 86 (85%) patients survived, and 15 (15%) died after discharge. Deaths were reported within 1 to 4 weeks after discharge: 6 subjects died during re-hospitalization, 6 at home, and 3 in a rehabilitation center. The multivariate regression analysis model, adjusted for all statistically significant indicators, and the ROC analysis showed the most significant predictors of 90-day post-hospital mortality and their threshold values. They include the Charlson comorbidity index >=4 points, lung damage according to computed tomography >=30%, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The analysis showed that 90-day post-hospital mortality depends on combinations of identified risk factors;a combination of two, three, and especially four risk factors statistically significantly is associated with patients' lower average survival time. Conclusion. The key risk factors for 90-day post-hospital mortality in elderly patients with asthma after severe COVID-19 include the Charlson comorbidity index, lung damage >=30% according to computed tomography, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The 90-day post-hospital survival rate is correlated with the number of risk factors identified in patients. The effect of asthma severity on 90-day post-hospital mortality in elderly patients was not observed.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

evaluation of hematological abnormalities in subjects vaccinated with bnt162b2 in a longitudinal cohort of the coRe study

Background: Vaccination is considered the most effective preventive strategy to fight COVID-19. The aim of this study was to evaluate two critical concerns about: 1) the kinetic response of IgG and IgM, and: 2) the hematological abnormalities in a longitudinal cohort of health-care workers (HCW) who had received 2 doses of BNT162b2 mRNA-based vaccine. Method(s): Blood and nasopharyngeal swabs were collected from 46 volunteers' participants, previous written consensus, with presumable no symptoms of COVID-19. Anti-SARS-CoV-2 serum immunoglobulin G (IgG) and M (IgM) and hematological parameters were examined. Multivariable mixed-effects models for repeated measure analysis were adopted to evaluate time changes in IgG, IgM and hematological parameters, and to investigate associations with vaccination response. Result(s): Forty-six subjects (N.=46;31.8% men;68.2% women;mean age near 36 years-old) were enrolled among healthcare workers of IRCCS MultiMedica (Milan, Italy). Overall, increase in serological IgG concentration appeared mainly between 21-28 days after the 1st dose, whereas IgM did not reach positivity in all cases. Mean blood cells counts were in normal range but we observed a significant reduction of total white blood cells and absolute lymphocyte counts after the 1st dose, persisting until the day 28. The increase of monocytes and neutrophils the day after the 1st dose subsequently decayed significantly. Eosinophils concentration showed a tendency to increase over time. Peripheral blood smear showed a growing frequency of atypical lymphocytes (lympho-variants), and of plasmacytoid forms, whereas no difference was found in large granular lymphocytes (LGL), although a decay after the boost was evident. The stratification of subjects, relative to the timing of IgG increase, showed the occurrence of 3 different patterns after vaccination, namely early-responders (R+), late-responders (R-) and pauci-responders (PR) with a peculiar kinetics of hematological parameters. Lymphocytes were significantly associated with total IgG: lower in R+ and PR compared to R- (P=0.0193 and P=00054, respectively). Conclusion(s): In healthy subjects, anti SARS-CoV-2 vaccination induced a variety of non-pathologic abnormalities. The response to vaccination was not equal in the groups examined. In PR group a major difference occurred with respect to R- and R+. This work adds novel insight into the puzzle of changes induced by SARS-CoV-2 virus.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Clinical outcomes in asthmatic patients following COVID 19 infection

Background: COVID-19 disease caused by SARS-CoV-2, has changed life as we know it, causing millions of deaths worldwide. Reported risk factors for mortality include advanced age, obesity, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease. Although asthma is a chronic obstructive disease, most evidence reveals a protective effect between asthma, eosinophilia and COVID-19. La Paz University Hospital, in Madrid, has developed one of the largest cohorts in Europe, with more than 3500 patients with COVID-19. Our aim was to evaluate post-COVID-19 evolution at 6 and 12 months in asthmatic patients. Method(s): We selected the asthmatic patients in this cohort. We obtained information from their clinical history, including sex, age and comorbidities. We classified patients by T2 or non-T2 asthma and collected pre-COVID19 information: treatment, control (measured by asthma control test (ACT) and number of exacerbations), pulmonary lung function, eosinophils in blood and immunoglobulin E levels. Post-COVID-19 data after 6 and 12 months were recorded: symptoms (chest pain, cough, expectoration and dyspnea), ACT, number of exacerbations, the need to intensify the asthma treatment, and the pulmonary lung function. Result(s): Significant association was found between COVID-19 pneumonia in asthmatic patients and the risk of having chest pain after 6 months (p = 0.009). Fewer eosinophilic count was associated with dyspnea 6 months post-covid (p = 0.043). Asthmatic smokers had an increased risk of thromboembolism 12 months after COVID-19 (p = 0.025). Although significant association standards were not met nor demonstrated, thoracic pain was more frequent 6 months post-COVID-19 in non-T2 asthmatic patients (44.4%) than T2 patients (20.3%) (p = 0.064). Eosinophilic asthma (eosinophil counts higher than 250/ mcl), presented lower prevalence of chest pain 12 months post-COVID-19 (p = 0.081). Conclusion(s): This is the first study that demonstrates the association between risk of chest pain and dyspnea after 6 months in asthmatic patients with COVID-19 pneumonia. It was also found that if these patients smoked, there was an increased risk of thromboembolism at 12 months. Further studies, with a higher number of patients are needed to explore deeply the impact of COVID-19 in asthma outcomes.

Dupilumab efficacy and safety up to 52 weeks in adult and adolescent patients with eosinophilic esophagitis: Results from parts B and C of the randomized, placebo-controlled, three-part, phase 3 LIBERTY EoE TREET Study

Introduction (contexte de la recherche): In Parts A and B of the 3-part phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab 300 mg weekly (DPL qw) vs. placebo (PBO) demonstrated significant efficacy and acceptable safety up to 24 weeks (wks) in adults and adolescents with eosinophilic esophagitis (EoE). For patients (pts) who completed Parts A or B, Part C was an extended active treatment period for 28 wks. Objectif: To assess the safety and efficacy of DPL in pts who completed Part B and continued to Part C, up to 52 wks. Methodes: Of 80 DPL qw pts in Part B, 74 continued DPL qw in Part C (DPL/DPL). Of 79 PBO pts in Part B, 37 pts received DPL qw in Part C (PBO/DPL). Part B co-primary endpoints were proportion of pts achieving peak esophageal intraepithelial eosinophil (eos) count <= 6 eos/high power field (hpf) and absolute change from Part B baseline (BL) in Dysphagia Symptom Score (DSQ) score at Wk 24. Secondary endpoints included peak eos count, EREFS, and HSS grade and stage scores. In Part C, all co-primary and secondary endpoints were assessed at Wk 52 as secondary endpoints. Safety was also assessed. Resultats: Part B BL characteristics were similar across groups. At Wk 52 of Part C, 84.6% of DPL/DPL and 67.6% of PBO/DPL groups achieved peak eos count of <= 6 eos/hpf and mean (SD) absolute change from Part B BL in DSQ score was -30.26 (15.39) for DPL/DPL and -27.25 (11.46) for PBO/DPL pts. At Wk 52, peak eos count, EREFS, HSS grade and stage scores were reduced, compared with Part B BL, and EDP and T2 NESs were suppressed in DPL/DPL and PBO/DPL groups. Dupilumab demonstrated an acceptable safety profile in Part C;the most common (occurring >= 10%) treatment-emergent adverse events in DPL/DPL and PBO/DPL groups were injection-site reactions (13.5% and 10.8%), COVID-19 (9.5% and 10.8%) and nasopharyngitis (4.1% and 10.8%). Conclusion(s): As observed in Part A/C, dupilumab qw demonstrated persistent improvements in clinical, symptomatic, histologic, endoscopic and molecular features of EoE up to 52 wks and had an acceptable safety profile. PBO pts from Part B who received dupilumab in Part C showed similar efficacy to dupilumab qw pts of Part B.Copyright © 2023

New onset chronic spontaneous urticaria post COVID-19 vaccination in South Africa

Background: Chronic spontaneous urticaria (CSU) is a common chronic inflammatory disease. There have been small case series of new onset CSU post COVID-19 infection as well as reports of new onset CSU or worsening of existing CSU post COVID-19 vaccination. Dermatological side effects post COVID-19 vaccine are typically delayed, self-limiting urticaria. We have described the characteristics of patients who have developed new onset CSU post COVID-19 vaccination. Method(s): All patients referred to the UCT Lung Institute Allergy clinic from the initiation of the COVID-19 vaccine roll out (February 2021) were reviewed to identify patients that developed new onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, response to therapy, and available laboratory investigations were reviewed by clinic physicians. Result(s): We identified seven patients that developed CSU post COVID-19 vaccine. The median age of the cohort is 39 (IQR 32-45) and the majority are female (n = 5). The most common vaccine was the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (n = 6, 85.7%), and one patient received the Jansen Ad26.COV2.S vaccine. No patients had COVID-19 infection prior to vaccination and only one patient contracted COVID-19 post vaccination. The median time to the development of symptoms post vaccination was 14 days (IQR 2;44) and the median time to diagnosis was 90 days (IQR 45;120). Most patients (n = 4) reported angioedema and urticaria, one patient reported isolated angioedema, and two isolated urticaria. The median initial UAS7 score was 37.5 (IQR 24.5;46) and the initial CU-Q2oL score was 72 (IQR 56;76) indicating severe disease activity. All but one patient had a history of atopy with the most common diagnoses being allergic rhinitis (n = 5) and atopic dermatitis (n = 3). All patients had normal eosinophil counts and over half of the patients (n = 4) had an elevated total IgE level (median 26.4 [IQR 9.8;194]). All patients were HIV negative and one patient had positive Helicobacter pylori serology. All had normal serum protein electrophoresis, thyroid function (with negative thyroid autoantibodies), and negative antinuclear antibodies. All patients started on high dose antihistamine therapy with 71.1% having partial or no response to therapy. Conclusion(s): New onset CSU is a rare side effect of COVID-19 vaccination with poor response to high dose antihistamine therapy. It is important that allergists and physicians are aware of the possibility of new onset CSU post COVID-19 vaccine and further research is needed to identify risk factors.

What relationship between eosinophilia and covid19 prognosis?

Introduction: Since the discovery of SARS COV2 in 2019, several biological markers were reported as poor prognostic factors. Aim(s): Evaluate the value of eosinophil count (EC) on admission as a predictive marker of unfavorable outcomes. Patient and method: A retrospective study was conducted from January to July 2021, including 400 patients in the Covid department of Gabes university hospital. We compared the clinical data, lab findings, including inflammatory markers, radiological findings, course and severity (mortality, ICU admission, and need for mechanical ventilation) in 2 groups: patients with eosinophilia (G1 (n=57 cases)) to those without eosinophilia (G2 (n=343 cases)). Result(s): The median age was 67,7 years in G1 and 63,7 years in G2. The female sex was predominant in the G1 (52,6% of cases), while in the G2 the dominant sex was male (52,2%). The most common comorbidities in both groups were: diabetes (52,6% in G1 vs 29,7% in G2), hypertension (17,5% in G1 vs 40,2% in G2) and heart diseases (28% in G1 vs 13% in G2). Patients with eosinophilia had a higher CRP than G 2 (138 mg/dl vs 122 mg/dl). Severe and critical CT damage was important in G1 than G2 (49,1% vs 38,2% patients ;p=0,16). They also had a higher ICU admission and mortality (38,6% in G1 vs 27,4% in G2 ;p=0,08, 66,7% vs 37,3% ;p=3.10-6 respectively). The duration of ICU admission in G1 was shorter than G2 (the average hospitalization duration was 3,8 days in G1 vs 4,23 days in G2). G1 had higher mechanical ventilation (45,6%) than G1 (23,3%) (p=4.10-5). Conclusion(s): The eosinophil's count must be evaluated at the admission of the patients to know the prognosis and to improve the management.

SARS-CoV-2 severity prediction in young adults using artificial intelligence.

Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

SARS-CoV-2 severity prediction in young adults using artificial intelligence.

Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Bronchoalveolar lavage fluid characteristics in patients with persistent symptoms following COVID-19 infection

A significant number of patients suffer from persistent symptoms following COVID-19 infection. However, data regarding the immunopathological mechanisms and potential biomarkers are limited. We investigated the differential cell count in the bronchoalveolar lavage fluid (BALF) in a post-COVID cohort. Patients presenting at the Vienna General Hospital within six months of a COVID-19 infection were enrolled. All patients underwent pulmonary function tests (PFT) and low-dose HRCT at baseline and at 6 and 12 months after a COVID-19 infection. Patients with pathological findings on HRCT or impairment in PFT were offered a bronchoscopy with BALF differential cell count via FACS analysis. Out of the 305 patients enrolled, 29 underwent bronchoscopy with bronchoalveolar lavage. After a median of 84 days following initial diagnosis of COVID-19, 25 showed persistent symptoms including dyspnoea (62.1%), fatigue (10.3%) and chest pain (10.3%). 24 patients showed pathological findings on HRCT consistent with COVID-19. While 11 patients developed a restrictive lung disease defined as TLC < LLN, 18 patients showed a reduced diffusion capacity defined as DLCO < 80%. Differential cell counts revealed that some patients showed lymphocytosis (7/29), increased eosinophil counts (5/29) and elevated neutrophils counts (2/29) in the BALF. Our preliminary data show that 34.5% of patients with persistent changes on HRCT have an elevated immune cell count with lymphocytosis being the predominant pattern. The degree of alveolar lymphocytosis might correlate with the severity of restrictive lung disease and might facilitate treatment decisions in patients with persistent symptoms following COVID-19.

Are Lymphocytes and Eosinophils Associated with the COVID-19 Severity: A Large, Retrospective Study

OBJECTIVE: Coronavirus disease 2019 is an ongoing disease with high morbidity and mortality. We aimed to investigate the relationship between demographics, lymphocytes, eosinophils, and the coronavirus disease 2019 severity at hospital admission. MATERIAL AND METHODS: A retrospective, observational cross-sectional study was carried out with 5828 coronavirus disease 2019 patients between March 11, 2020, and November 30, 2020. Patients were divided into 3 groups according to where they were followed up as an indicator of disease severity, namely outpatients, inpatients, and critically ill patients. The patients' demographics and hemogram values on admission were recorded. The predictive accuracies of lymphocyte count, lymphocyte percentage, eosinophil count, and eosinophil percentage for predicting severity were determined using receiver operating characteristic curves. Logistic regression analysis was used to predict intensive care unit demand according to lymphocyte and eosinophil values. RESULT(S): Of the 5828 coronavirus disease 2019 patients, 4050 were followed up as outpatients, 1581 were hospitalized in a ward, and 197 were hospitalized in the intensive care unit. Lymphocyte count and lymphocyte percentage were significantly different between the groups, but the difference for eosinophil count and eosinophil percentage was not significant as it was for lymphocytes. Cutoff values for lymphocyte count (1.0 x 109/L), lymphocyte percentage (22%), eosinophil count (0.052 x 109/L), and eosinophil percentage (0.08%) were found to indicate a high risk for intensive care unit admission. Coronavirus disease 2019 patients >55 years of age, with a lymphocyte count <1.0 x 109/L, a lymphocyte percentage <22%, and an eosinophil percentage <0.08% had a 2-fold higher risk of requiring intensive care unit management. CONCLUSION(S): Lymphocyte counts and percentages are quick and reliable biomarkers for predicting coronavirus disease 2019 severity and may guide physicians for proper management earlier.Copyright © Author(s).

New-Onset Chronic Spontaneous Urticaria Post Covid-19 Vaccination in South Africa

INTRODUCTION Chronic spontaneous urticaria (CSU) is a common chronic inflammatory disease. There have been small case series of new onset CSU post-COVID-19 infection and reports of new onset or worsening of existing CSU post COVID-19 vaccination. A dermatological side-effect post COVID-19 vaccine is typically delayed, self-limiting urticaria. We have described the characteristics of patients who have developed new-onset CSU post COVID-19 vaccination. METHOD All patients referred to the Allergy Clinic since the initiation of the COVID-19 vaccine roll-out in South Africa were reviewed to identify patients who had developed new-onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, response to therapy and available laboratory investigations were reviewed by clinic physicians. RESULTS We identified seven patients who developed CSU post COVID-19 vaccination. The median age of the cohort is 39 (IQR 32-45) and the majority are female (n = 5). The most common vaccine was the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (n = 6;85). The median time to the development of symptoms post-vaccination was 14 days (IQR 2;44) and the median time to diagnosis was 90 days (IQR 45;120). The median initial UAS7 score was 37.5 (IQR 24.5;46) and the initial CU-Q2oL score was 72 (IQR 56;76), which indicated severe disease activity. All but one patient had a history of atopy, with the most common diagnoses being allergic rhinitis (AR) (n = 5) and atopic dermatitis (AD) (n = 3). All the patients had normal eosinophil counts and more than half of the patients (n = 4) had an elevated total IgE level (median 26.4 [IQR 9.8;194]). All of the patients were HIV-negative. All of them had normal serum protein electrophoresis, thyroid function (with negative thyroid autoantibodies) and negative antinuclear antibodies. All of them started on high-dose antihistamine therapy, with 71.1% having partial or no response to the therapy. CONCLUSION New-onset CSU is a rare side-effect of COVID-19 vaccination, with poor response to high-dose antihistamine therapy. It is important that allergists and physicians are aware of the possibility of new-onset CSU post COVID-19 vaccination and further research is needed to identify any risk factors.

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.Copyright © The Author(s) 2022.

Spotting the Needle Amongst the Haystack - When Asthma Isn't Asthma

Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.

Eosinophilic Oesophagitis in Children: A Single Uk Tertiary Centre Experience

The incidence of Eosinophilic Oesophagitis (EoE) is increasing worldwide in the paediatric population. Management of these children is complex, and includes elimination diet (2/4/6 food), steroids etc. It is recommended to perform endoscopies between each reintroduction to assess disease activity. In our centre dietary exclusion is the standard practice. Since 2019 we follow a step-up approach with regards to elimination diet starting with 2 food exclusion diet (FED) and building up as required. Food is reintroduced gradually with significant dietetic support and proactive monitoring including endoscopy. Objectives We looked at the outcomes of children with EoE referred to Maidstone and Tunbridge Wells NHS Trust from Kent and East Sussex. Methods Retrospective review of case notes of paediatric patients diagnosed with EoE between January 2015 and December 2020. Data collected included symptoms, endoscopy findings and histology at diagnosis and compared the same after dietary intervention. Results 21 patients were diagnosed with EoE between January 2015 and December 2020 between 5-16 yrs Median age at diagnosis 11years. Frequently seen in boys (65%). Dysphagia was the predominant symptom (76%) followed by vomiting (60%), abdominal pain (50%), and choking (20%). Features of EoE were seen during endoscopy in 71% and oesophagus looked endoscopically normal in 29% of patients. Diagnosis was made on eosinophil count as per ESPGHAN guidance. The frequency and timing of repeat endoscopies following dietary intervention varied due to a multitude of factors including COVID-19 restrictions (between 4-9 months median 4 months). Histological remission (Eosinophils <15 pHPF) was achieved in 15/21 (70%) of patients. 7/10 children on 2FED, 3/3 patients on 4FED and 5/5 children on 6FED achieved histological resolution. The 6FED group took significantly longer to identify the causative food, establish long term dietary management and required more endoscopies. Food was reintroduced gradually on an individual basis with the aim of introducing back all food groups. 13/15 continue to be on milk free diet, 5/15 remain on milk and wheat free diet, 1/15 on soya and egg free diet and the other patient remains on 4FED (parental choice). 2 patients have started steroids due to on-going symptoms findings on surveillance endoscopy and histological following re-introduction. Summary and Conclusion Dysphagia was the predominant symptom in our cohort of patients. Furrowing and oedema was the major finding during endoscopy. With dietary exclusion endoscopic resolution was seen in 62% and histological resolution seen in 70% of patients at first surveillance endoscopy. Re-introduction continues to remains a major challenge and we have not been able to introduce all the food groups in any of our patients due to either symptoms or recurrence on endoscopy/histology.

Idiopathic Hypereosinophilic Syndrome Diagnosed in an Infant: A Case Report

Introduction: Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by persistent eosinophilia (>1.5 x 109/L) for >=6 months, tissue infiltration with end-organ damage, and exclusion of known causes for hypereosinophilia. It is mainly observed in adults, and rarely in children. We report, to our knowledge, the first case report of IHES in an infant. Case Description: A 5-month-old male presented with severe failure to thrive and malnutrition. His hospitalization was complicated by acute kidney injury, pulmonary edema requiring intubation, pseudomonas bacteremia with concomitant tibial osteomyelitis, COVID-19 infection, and bradycardic arrest requiring CPR. Notably, patient had persistent eosinophilia (maximum 11.4 x 109/L) (Table 1). Parasite testing was negative. Immune work-up was normal (Table 1). Primary immunodeficiency panel testing of 407 geneswas negative. Endoscopy revealed eosinophilia in the sigmoid colon and rectum. Bone marrow biopsy revealed a low normocellular bone marrow (70%) with maturing trilineage hematopoiesis and increased eosinophils and eosinophil precursors (approximately 50% of nucleated cells). A FISH panel was negative for PDGRFRA/4q12, PDGRFRB/5q33, FGFR1/8p12, and ETV6/12p13 gene regions. The patient was diagnosed with IHES and started on steroids at 0.5 mg/kg/day. Hydroxyurea was added due to up-trending eosinophil count despite steroid therapy. Three months post-diagnosis, he is doing well off medications, with most recent eosinophil count being 2.1 x 109/L. Discussion(s): Hypereosinophilia in children is most commonly due to secondary causes such as atopic dermatitis, parasitic infections, neoplasms, graft-versus-host disease, sickle cell disease, and immunodeficiency. Once the above diagnoses have been excluded, IHES should be considered, especially in patients with evidence of end-organ damage. Copyright © 2022

Real-World Effectiveness of Dupilumab in Asthma: Findings from the Us Advantage Study

Introduction: Real-world evidence on patients with moderate-to-severe asthma treated with dupilumab is limited. Patients included in clinical trials may differ from the ones seen on a clinical office setting. The objective of our study was to characterize real-world effectiveness of dupilumab in US, as an add-on treatment in patients with moderate to severe asthma. Method(s): We retrospectively included patients (>=12 years of age) diagnosed with asthma, initiating dupilumab (index) between November 2018 to September 2020, with 12 months pre- and post-index information. The study employed a pre-post self-control design (TriNetX Dataworks, USA). Asthma exacerbation rates before vs. after dupilumab initiation were analyzed using Generalized Estimating Equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses on asthma exacerbations adjusted for COVID-19 confounding effects were performed using natural cubic splines to allow for time-varying effect estimates during pre- and post-pandemic time periods. Result(s): A total of 2400 patients initiating dupilumab met all study criteria and 75.3% were biologic naive. Dupilumab reduced risk of asthma exacerbations by 38% (IRR: 0.62 [95% confidence interval: 0.58-0.65], P=<.0001). Significant reductions in asthma exacerbations were observed in patients with at least 1 or 2, pre-index, asthma exacerbations, by eosinophil count categories, and when adjusted for impact of COVID-19 (Table-1) Conclusion(s): The US ADVANTAGE study demonstrated real-world effectiveness of dupilumab in reducing asthma exacerbation among patients 12 years and older in US clinical practice. These findings are generally consistent with data from previous pivotal clinical trials with dupilumab. Copyright © 2022

Clinical Characteristics of Strongyloidiasis during the Covid-19 Pandemic: Systematic Scoping Review

INTRODUCTION: Reactivation of Strongyloides stercoralis related to COVID-19 infection or treatment has been an emerging topic of interest, although characteristics of Strongyloides infection in COVID-19 patients are not yet well characterized. This study aims to summarize the existing evidence of Strongyloides infection in COVID-19 patients and figure out the future areas of research. METHOD(S): According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including"Strongyloides," "Strongyloidiasis," and "COVID-19," from the inception of these databases to June 5, 2022. RESULT(S): A total of 104 articles were found. After excluding duplication and thorough reviews, 11 articles, including two observational studies, one conference , and nine case reports or series, were included. Two observational studies focused on revealing the prevalence of Strongyloides screening in COVID-19 patients and clinical follow-up. One study from Spain, including 227 cases of COVID-19 and Strongyloides co-infection, noted that four patients developed critical hyperinfection leading to the expiration of one patient. Among the included cases, patients were mostly from low- or middle-income countries (LMICs) who suffered from severe or critical COVID-19. 90% received 6mg/day dexamethasone for 7-10 days or higher prednisone-equivalent doses of corticosteroids. 60% and 20% had Strongyloides hyperinfection and disseminated infection, respectively. Interestingly, patients had either eosinopenia or normal eosinophil counts while they were treated for COVID-19, and they were likely to develop eosinophilia later in the course leading to the diagnosis of Strongyloidiasis. CONCLUSION(S): This systematic review summarizes the clinical characteristics of Strongyloidiasis in COVID-19 infection. Likely due to COVID-19-related eosinopenia and the effect of corticosteroids, patients may not necessarily have overt eosinophilia despite the parasitic infection. Developing a Strongyloides screening strategy for COVID-19 patients based on patients' demographics and origins may help diagnose the condition. While further studies to identify risks and precipitants associated with the onset of Strongyloidiasis in crucial, increased awareness of the critical condition is warranted.