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.

Scientific rationale of Indian AYUSH Ministry advisory for COVID-19 prevention, prophylaxis, and immunomodulation

The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

Maxillary osteomyelitis secondary to mucormycosis, a sequel of COVID-19: a clinical case report

Introduction: One of the consequences of COVID-19 is the incidence of mucormycosis in the jaws and subsequent osteomyelitis in patients with undiagnosed or uncontrolled comorbidities, such as diabetes mellitus and associated immunosuppression. Case Report: A 52-year-old male patient with a history of COVID-19 two months ago presented a painful ulcerative lesion of insidious onset in the palatal raphe measuring approximately 2 mm. He referred to numbness of the palatal region of one month of evolution. During the physical examination, purulent content, multiple pustules in the anterior maxillary buccal mucosa, and mobility of upper anterior teeth were observed. The CT revealed isodense bilateral images in maxillary and ethmoidal sinuses, bone sequestrations, and partial loss of anterior vestibular cortical bone. Laboratory tests revealed no abnormality, except for HbH1c: 10.2gr/dl. The patient was hospitalized for control of newly diagnosed diabetes mellitus. Maxillary incisional biopsy was performed, and microscopic analysis showed a mixed inflammatory infiltrate, fibrin deposits with eosinophilic and birefringent ribbon-like hyphae, branched at right angles, compatible with maxillary osteomyelitis secondary to mucormycosis. The treatment started with antifungal and intravenous antibiotics, followed by surgical cleaning under general anesthesia. The patient progressed favorably. Conclusion(s): Immunosuppression resulting from COVID-19 and/or uncontrolled systemic diseases can condition the appearance of rare opportunistic microorganisms causing infections such as mucormycosis. Early diagnosis and treatment make a difference in the morbidity and mortality of patients.

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.

Eosinophil Recovery in Hospitalized COVID-19 Patients is Associated with Lower Rates of ICU Admission and In-Hospital Mortality: An Observational Cohort Analysis

Background Admission eosinopenia (<100 cells/μL) is associated with poor clinical outcomes in hospitalized COVID-19 patients. However, the effects of eosinophil recovery (defined as reaching ≥50 eosinophils/μL) during hospitalization on COVID-19 outcomes have been inconsistent. Methods The study included 1,831 patients admitted to UCLA hospitals between February 2020 and February 2021 with PCR-confirmed COVID-19. Using competing risk regression and modeling eosinophil recovery as a time-dependent covariate, we evaluated the longitudinal relationship between eosinophil recovery and in-hospital outcomes including ICU admission, need for mechanical ventilation, and in-hospital mortality. All analyses were adjusted for covariates including age, BMI, tobacco smoke exposure, comorbidities known to be risk factors for COVID-19 mortality, and treatments including dexamethasone and remdesivir. Results Eosinophil recovery was evaluated in patients with <50 eosinophils/μL on admission (n=1282). These patients cumulatively amassed 11,633 hospital patient-days;3,985 of those days qualified as eosinophil recovery events, which were represented by 781 patients achieving at least one instance of eosinophil recovery during hospitalization. Despite no significant difference in the rate of mechanical ventilation, eosinophil recoverers had significantly lower rates of in-hospital mortality (aHR: 0.44 [0.29, 0.65], P=0.001) and ICU admission (aHR: 0.25 [0.11, 0.61], P=0.002). Conclusion Trending eosinophil counts during hospitalization is simple and can be performed in resource-limited healthcare settings to track the inflammatory status of a patient. Lack of eosinophil recovery events can identify those at risk for future progression to severe COVID.

Correlation between laboratory findings and clinical severity among the COVID-19 patients in the tertiary care centre

Background: Coronavirus is a highly infectious novel virus we are in urge to know more about their clinical characteristics and laboratory findings for the characterization and selection of treatment protocol. Methods: Prospective, single centre study. Two months data was collected, clinical characteristics data from patient case sheet and the laboratoryvalues from the Hospital Information System (HIS) for the month of July and August 2020. Results: Of 462 patients, 55 (11.9%) are falls under asymptomatic category, 194 (42%) are in mild category, 167 (36.1%) are in moderate category and 46 (10%) in severe category. Fever 230 (49.8%) and cough 211 (45.7%) was most common clinical symptom with p value < 0.01. Non-severe vs severe, 340 (73.6%) and 201 (43.5%) showed decreased in eosinophil count and absolute eosinophil count, 125 (27.1%) and 80 (17.3%) patient showed decrease in lymphocyte count and absolute lymphocyte count, 200 (43.3%) showed increase in neutrophil count with a significance of p value >0.05.186 (40.3%) patients had one or more co-morbidities. Laboratory findings between Asymptomatic VS symptomatic, showed significance changes in neutrophil, lymphocyte, Aspartate aminotransferase, Alkaline phosphatase, globulin values (p value <0.05). Conclusion: Clinical severity categorization at the time of admission was very helpful for the treating doctors in proper understanding of disease progression and appropriate treatment of the patient. Presence of co-morbidity, abnormal laboratory values, old age group patients, higher Computed Tomography score, higher mortality rate are seen more in patients who were in clinical severity grade severe category than in non-severe category patients.

IgM Multiple Myeloma Presenting With Diarrhea

Introduction: IgM Multiple Myeloma (MM) is a rare subtype of MM consisting of <1% cases of MM. It is distinguished from Waldenstrom Macroglobinemia, which also produces IgM, by the absence of somatic mutation MYD88. We present a patient with a chief complaint of diarrhea which unknowingly led to his hematological diagnosis Case Description/Methods: A 64 year old male with RA-SLE overlap syndrome on steroids, and recent COVID19 pneumonia, had presented with 5 episodes of watery diarrhea every day and 40 Ib weight loss within 2 months. CT revealed small bowel enteritis and stool studies, including C. diff, cultures, ova and parasites were negative. Diarrhea persisted despite antibiotics, therefore an EGD and Colonoscopy were performed which showed duodenal lymphangiectasia and a normal colon. Duodenal biopsy revealed eosinophilic deposits in the villous lamina propria which stained for IgM and stained negative under congo red ruling out amyloidosis. SPEP and a bone marrow biopsy revealed monoclonal IgMspikes and plasma cells in the bone marrow suggesting MMalong with a co-existing population of CLL. Next-generation sequencing was negative forMYD88, supporting IgM MM instead of Waldenstrom. He developed a protein-losing enteropathy with dramatic hypoalbuminemia (albumin 0.9) and lower extremity edema and DVTs. He was started on chemotherapy and frequent albumin infusions. His diarrhea completely resolved, however not in time, as his other medical comorbidities lagged behind and he developed anasarca and continued to deteriorate. Discussion(s): Plasma cell dyscrasias such as IgM MM or more commonly Waldenstrom have rarely been reported to cause GI symptoms. GI involvement can include direct GI infiltration of plasma cells, IgM deposition, or the finding of a plasmacytoma. It has been speculated that IgM deposits can lead to interstitial viscosity and obstructive lymphangiectasia leading to diarrhea and a protein-losing enteropathy as in our patient. Protein loss has led him to have hypoalbuminemia and possibly loss of antithrombotic proteins that have caused DVTs. Few case reports have suggested that treating the underlying cause with chemotherapy stops diarrhea entirely. Although our patient's diarrhea ceased, we believe that it was not in time for him to entirely recover from the later complications of the disease. We hope that this case can help clinicians to attempt prompt treatment of patients when they find GI specimens showing IgM deposits and they suspect a plasma cell dyscrasia.

Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection.

OBJECTIVE: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. METHODS: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients' clinical demographic characteristics, laboratory findings, and clinical outcomes. RESULTS: COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. CONCLUSIONS: COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.

Machine learning uncovers blood test patterns subphenotypes at hospital admission discerning increased 30-day ICU mortality rates in COVID-19 elderly patients

Introduction: Since March 2020, a number of SARS-CoV-2 patients have frequently required intensive care unit (ICU) admission, associated with moderate survival outcomes and an increasing economic burden. Elderly patients are among the most numerous, due to previous comorbidities and complications they develop during hospitalization [1]. For this reason, a reliable early risk stratification tool could help estimate an early prognosis and allow for an appropriate resources allocation in favour of the most vulnerable and critically ill patients. Method(s): This retrospective study includes data from two Spanish hospitals, HU12O (Madrid) and HCUV (Valencia), from 193 patients aged > 64 with COVID-19 between February and November 2020 who were admitted to the ICU. Variables include demographics, full-blood-count (FBC) tests and clinical outcomes. Machine learning applied a non-linear dimensionality reduction by t-distributed stochastic neighbor embedding (t-SNE) [2];then hierarchical clustering on the t-SNE output was performed. The number of clinically relevant subphenotypes was chosen by combining silhouette and elbow coefficients, and validated through exploratory analysis. Result(s): We identified five subphenotypes with heterogeneous interclustering age and FBC patterns (Fig. 1). Cluster 1 was the 'healthiest' phenotype, with 2% 30-day mortality and characterized by moderate leukocytes and eosinophils. Cluster 5, the severe phenotype, showed 44% 30-day mortality and was characterized by the highest leukocyte, neutrophil and platelet count and minimal monocytes and lymphocyte count. Clusters 2-4 displayed intermediate mortality rates (20-28%). Conclusion(s): The findings of this preliminary report of Eld-ICUCOV19 patients suggest the patient's FBC and age can display discriminative patterns associated with disparate 30-day ICU mortality rates.

The effect of functional exercise along with online nutritional education on inflammatory biomarkers in children with autism spectrum disorder during COVID-19 pandemic: a randomized clinical trial

Background and Objectives: Autism spectrum disorder (ASD) is a neuro-developmental disorder which is mostly caused by deficits in social interactions. Lack of physical activity and poor nutritional habits are common problems in these patients which may be exaggerated by the Covid-19 pandemic. The study aims to assess the effect of functional training along with online nutrition education on inflammatory biomarkers in children with ASD. Subjects and Methods: In this randomized controlled clinical trial, 80 children with ASD (age=9.73+or-1.29 years, weight=49.94+or-2.08 kg, height=146.08+or-40 cm, body mass index=24.71 +or-1.48 kg/m2) were randomly divided into four groups of training, education, training+ education, and control. The interventions lasted for 8 weeks. The inflammatory biomarkers including white blood cell (WBC) count, C-reactive protein (CRP) level, neutrophil count, eosinophil count, and basophil count were assessed (using blood samples collected from antecubital vein) before and after the interventions. Results: There was no significant difference between the groups before the interventions (P>0.05). After the intervention, the results showed a significant decrease in WBC (P<0.001), CRP (P=0.001), neutrophils (sig.=0.009), and eosinophil (P=0.003) in all groups. Basophil count decreased in all groups (P=0.01) except in the education group. Conclusion: Functional training and online nutrition education are beneficial interventions for management of inflammatory biomarkers in children with ASD which can be used during the Covid-19 pandemic.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

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.

Dupilumab as a steroid-sparing treatment option in pediatric severe asthma and chronic rhinosinusitis with nasal polyps

Case report Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe asthma in adults. Both diseases share key pathophysiological mechanisms that can involve type-2 inflammatory pathways. However, this is an uncommon presentation in pediatric patients. Dupilumab, a fully human monoclonal antibody against IL-4Ralpha, inhibits IL-4/ IL-13 signaling, which are key drivers of type-2 inflammation and interfere with both eosinophilic and allergic pathways. It is approved for patients >= 12-year- old with moderate to severe uncontrolled asthma, but its approval in CRSwNP is limited to adults. We report a case of a 12-year- old boy with severe uncontrolled asthma and highly symptomatic CRSwNP referred to our center in May 2021. He was sensitized to house dust mite and pollens, and a specific immunotherapy had been tried previously. He was treated with high dose inhaled corticosteroid, long-acting beta agonist, long-acting muscarinic antagonist, montelukast and daily intra-nasal corticosteroids. Furthermore, a bilateral endoscopic sinus surgery with polypectomy was performed in April 2021. Despite adherence to medication and surgical treatment, both diseases were uncontrolled with frequent exacerbations requiring unscheduled visits and multiple systemic corticosteroid courses. This led to failure to thrive and several missed school days. Oral corticosteroid (OCS) tapering was unachieved due to symptoms rebound and so maintenance therapy with prednisolone 10mg daily was attempted, with only a slight improvement. High levels of eosinophils (1010 cells/muL), FeNO (122 ppb) and IgE (2255 kU/L) were present. Treatment with subcutaneous dupilumab was started in July 2021. A clinical and analytical improvement was evident at the 3-month evaluation (Table 1). He was able to stop prednisolone, and no clinically relevant exacerbations occurred. He also was fully vaccinated and had an asymptomatic COVID-19 infection in December 2021. Patients with CRSwNP and comorbid asthma have a higher disease burden than patients with each disease alone. In this adolescent, dupilumab was effective as an add-on treatment, for both severe asthma and CRSwNP. It led to disease control, OCS withdrawal, reduced eosinophilic inflammation, improved lung function, smell recovery and absence of exacerbations during follow-up. Dupilumab, targeting the type 2 inflammatory process, may allow a better management of pediatric patients >=12 years old with severe CRSwNP and comorbid asthma. (Table Presented).

'Breaking' news: A pediatric case of leukocytoclastic vasculitis after SARS-CoV-2 vaccination

Case report In May 2021, the European Medicines Agency (EMA) approved the administration of the mRNA BNT162b2 vaccine (Pfizer/BioNTech) in adolescents aged 12-15 years, in the form of a two-doses-primary course three weeks apart, with a booster dose after five months. Few adverse events have been observed in vaccinated children -mainly fever, myalgia, or local edema at the injection site. Conversely, delayed cutaneous reactions are little reported in adults and even rarer in pediatric age. A 12-year-old boy, with no previous cutaneous or autoimmune diseases nor allergic reactions to previous vaccines or drugs, came to our attention because of a cutaneous rash, which started on his right arm two days after his first dose of Pfizer/BioNTech vaccine. The rash was flat, erythematous, and purpuric, with subsequent bruise appearance and spontaneous resolution. Lesions took over on the front side of his arms and shoulders until a month after the vaccine. Urine and blood tests -including blood cell count, flow cytometry, plasma biochemistry, inflammatory index, autoantibodies, coagulation, and platelets aggregation test -did not show significant alterations. Grass pollen monosensitization was detected. Biopsy of the lesions showed 'modest perivascular lymphohistiocytic infiltrate and focal infiltration of vascular walls with swollen endothelium' with 'occasional eosinophils, scattered neutrophil granulocytes, and erythrocytes in interstitial areas,' compatible with leukocytoclastic vasculitis. Epidermidis was undamaged, and the direct immunofluorescence showed fibrinogen deposits in superficial-to-middle dermis vessels. Further tests highlighted a high immune response to the vaccine without previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. No therapies were needed, and the boy experienced no other side effects undergoing his second dose. Few leukocytoclastic vasculitis cases after SARS-CoV-2-vaccination have been reported in adults, primarily flares of previously known vasculitis. A role for induced spike glycoprotein as a pseudovirion docking to specific vascular receptors has been suggested, too. To our knowledge, no similar cases were described currently, neither in such young patients nor with such atypical, focal lesions. Further studies are needed to identify the pathogenesis and possibly prevent the onset of this adverse reaction.

A Rare Case Of Eosinophilic Myocarditis Due To Subacute Sars-cov-2 Illness

Background: Eosinophilic myocarditis is a rare inflammatory cardiomyopathy with a poor prognosis. SARS-CoV-2 (COVID-19) illness has been associated with myocarditis, particularly of lymphocytic etiology. Although there have been cases of eosinophilic myocarditis associated with COVID-19 vaccination, there have been few reported cases secondary to COVID-19 illness, with the majority being diagnosed via post-mortem autopsy. Case: A 44-year-old woman with no significant medical history other than recent COVID-19 illness 6 weeks prior presented with progressive dyspnea. Patient developed acute dyspnea and diffuse pruritic rash after taking hydroxyzine. Labs were significant for mild eosinophilia. Echocardiography showed biventricular systolic dysfunction with left ventricular ejection fraction of 40%, and a moderate pericardial effusion that was drained percutaneously. She underwent left heart and right heart catheterization showing elevated biventricular filling pressures, Fick cardiac index of 1.6 L/min/m2, and no coronary disease. She was started on intravenous diuretics and transferred to our facility for further management. Her course was complicated by cardiogenic shock requiring intra-aortic balloon pump (IABP) support. Mixed venous saturations continued to decline and the patient was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The patient underwent endomyocardial biopsy (EMB) showing marked interstitial infiltration of eosinophils and macrophages with myocyte injury (see image). She was intubated with mechanical ventilation as well due to worsening pulmonary edema and hypoxemia. She was started on intravenous steroids with improvement of hemodynamics and myocardial function and eventually VA- ECMO was decannulated to low-dose inotropic support which in turn was ultimately weaned after 3 days of mechanical support. Conclusion(s): Eosinophilic myocarditis is a rare and under-recognized sequela of acute COVID-19 infection associated with high mortality rates. It requires prompt diagnosis and aggressive supportive care, including temporary mechanical circulatory support. There are few literature-reported cases of COVID-19 myocarditis requiring use of both IABP and VA-ECMO, none of which were used in biopsy-proven eosinophilic myocarditis, with most of these cases resulting in either fatal or unreported outcomes. Most cases of covid myocarditis required IV glucocorticoids therapy in conjunction with IVIG or interferon therapy. Here, we present a rare case of cardiogenic shock secondary to biopsy-proven eosinophilic myocarditis associated with recent COVID-19 illness with a survival outcome after temporary use of IABP and VA-ECMO support, as well as aggressive immunosuppressive therapy.Copyright © 2022

Outcomes of chronic spontaneous urticaria in a patient with non-Hodgkin's lymphoma and SARS-Cov- 2 infection: Efficacy of treatment with omalizumab

Case report Background: Association of chronic spontaneous urticaria (CSU) with malignancies and worsening of urticaria during COVID-19 have been reported. The efficacy of treatment of CSU with omalizumab in the context of malignancies or COVID-19 is not well established. Method(s): Case report of a patient followed for 9 years with CSU. Data collected from Medical Records and interviews during consultations. Result(s): Female, 29 years-old, came to clinic in 2013 for investigation, diagnosed with CSU. She also presented mild asthma, allergic rhinitis and history of urticaria after taking amoxicillin. She had a positive autologous serum skin test, and positive skin tests to dust mite, cat, cockroach, peanut and milk. Her total IgE was 227IU/ mL. Anti-nuclear and anti-thyroid antibodies were negative;ERS 13mm, blood eosinophils 300/mm3, and stool exam negative for parasites. She showed no response to second generation antihistamines up to fourfold doses, with UCT < 6 and CU-QoL = 89. After 6 months, omalizumab was added at 300 mg subcutaneously, every 4 weeks. The patient showed immediate reactions after the two applications of omalizumab: first, diffuse pruritus and throat tightness;second, worsening of urticaria and pruritus, requiring iv medications. Treatment with omalizumab was stopped, she was kept on fourfold dose of bilastine with partial control of symptoms. In 2016, she presented worsening of urticaria (UCT = 1), weight loss of 6kg/2 months, daily fever and enlarged cervical lymph nodes, and was diagnosed with diffuse large B-cell non-Hodgkin's lymphoma. Following chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab, she presented complete resolution of urticaria. Two years after remission of the lymphoma, in 2019, she presented recurrence of urticaria, and treatment with fourfold dose of bilastine was reinitiated with control of symptoms (UCT = 16). Investigation ruled out recurrence of lymphoma. In May 2021, she was diagnosed with SARS-CoV- 2 infection. Symptoms of COVID-19 were runny nose and low grade fever, however urticaria got worse and no longer responsive to bilastine. Treatment with omalizumab was attempted, with no reactions and good efficacy after the first dose, with an UCT = 15, and urticaria remains controlled on treatment with omalizumab to present. Conclusion(s): In this report, we highlight the efficacy and safety of using omalizumab in a patient with refractory CSU associated with neoplasia and SARS-CoV- 2 infection.

Association of macrophage inflammatory protein-1beta with the recovery process in COVID-19

Background: Recovery from coronavirus disease 19 (COVID-19) is a gradual process that depends on the disease severity. Immunologic changes that precede and relate clinical symptoms may predict the course of COVID-19 and final outcome. Our goal was to determine prognostic markers of COVID-19 improvement. Method(s): The study included hospitalized patients from the ages 31-72 with moderate to severe COVID-19. All biomarkers were assessed at three checkpoints starting from the first day of hospitalization (day 0), continuing on day 8, and between 40-50 day. Luminex xMAP technology and the Bio-Plex Pro Human Cytokine 17-plex assay was used for quantitative evaluation cytokines and chemokines in peripheral blood of COVID-19 patients. The comparative study was done in combination with clinical data. Univariate and multivariate analyses of data were delivered. Finally, a fuzzy logic model for decision support was proposed and validated for explored data. Result(s): Macrophage inflammatory protein-1beta (MIP1b) was inversely related to COVID-19 evolution. MIP1b significantly higher on day 8 compared to day 0 (p < 0.0001) correlated with clinical improvement and predicted a successful course of the disease. It was also associated with the significant increase in TNF-alpha (p = 0.03), and decrease in IL-10 (p < 0.0001), and IL-6 (p = 0.01). The increase in MIP1b on day 8 correlated positively with eosinophil and lymphocytes counts and negatively with inflammatory mediators (ferritin, procalcitonin, fibrinogen, CRP). Moderately positive correlation between MIP-1b and TNF-alpha was noted, in parallel. Tested the statistical and machine learning predictors exhibited sensitivity to MIP1b input, improving the ROC curve compared to the classification models trained without MIP1b. Conclusion(s): This finding next to already known indicators such as IL-6, eosinophil and lymphocytes counts, highlight a role of MIP1b as a marker of good prognosis in COVID-19 and provide a novel insight into this as a potential diagnostic and therapeutic target.

Persistent allergic respiratory symptoms induced by food allergy: Report of two cases

Case report Dust is a known mixture and carrier of multiple allergens and an epidemiologic study demonstrated the presence of peanut proteins in school cafeterias and classrooms, suggesting that schools may play an important role in exposure to environmental food allergens. While inhalation of food allergens is a known trigger of IgE-mediate acute respiratory reaction as rhinitis and wheezing, little is known about persistent allergic asthma and/or rhinitis induced by chronic inhalation of food allergens. Here we report two cases of teenagers with nuts allergy presenting with persistent respiratory symptoms when exposed to closed and dusty environments. The first case concerns a 12-year-old boy allergic to walnut and hazelnut (specific IgE > 100 and 81.70 kU/l, respectively). For some years he has had a persistent mild asthma, frequent nasal occlusion and rhinorrhea, without any allergic sensitization to aeroallergens. Symptoms occurred exclusively during school period when he required maintenance therapy with inhaled and nasal steroids. He was asymptomatic and did not need any treatment during summer. During the lockdown period due to Covid-19 pandemic, he did not attend school for several months and he was able to discontinue inhaled corticosteroid therapy without recurrence of asthma and rhinitis symptoms. Asthma recurred after he returned to school, but with only mild intermittent symptoms, probably thanks to the use of masks and the frequent airing of the classrooms. On a single occasion he experienced nasal occlusion and rhinorrhea after that a parent had eaten hazelnut cream in the same room where he was. The second case deals with a 17-year-old boy with a history of several food allergies (milk, egg, wheat, banana, nuts, hazelnuts) and mild persistent asthma in absence of sensitization to aeroallergens. He successfully underwent oral desensitization for milk, egg and wheat in previous years. Asthma symptoms improved over the years together with progressive development of oral tolerance to food allergens for which oral immunotherapy had been done. On the other hand, he referred persistence of allergic rhinitis especially during the school year and his symptoms got worse in classroom. Exhaled nitric oxide was quite increased with evidence of eosinophils in nasal smears. In-vitro and in-vivo tests only detected food allergens sensitizations, in particolar to walnuts and hazelnuts (specific IgE were 61.00 and 55.50 kU/l respectively). These two clinical cases suggest that food allergens might be causative agents of allergic persistent asthma and/or rhinitis as aeroallergens do.