Ethnic, racial and migrant inequalities in respiratory health

Disparities in the incidence, prevalence, and morbidity and mortality rates of many respiratory diseases are evident among ethnic groups. Biological, cultural and environmental factors related to ethnicity can all contribute to the differences in respiratory health observed among ethnic minority groups, but the inequalities observed are most commonly due to lower socioeconomic position. People who migrate within a country or across an international border may experience an improvement in respiratory health associated with improvements in socioeconomic position. However, migrants may also experience worse health outcomes in destination countries, as they are faced by barriers in language and culture, discrimination, exclusion and limited access to health services. While some high-quality studies investigating ethnicity and respiratory health are available, further research into ethnic differences is needed. Improving the recording of ethnicity in health records, addressing barriers to accessing respiratory healthcare and improving cultural literacy more generally are some of the ways that inequalities can be tackled.Copyright © ERS 2023.

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Mild COVID-19 outcomes in adults with inborn errors of immunity: a single-center experience

Currently, 640 million cases of coronavirus disease 2019 (COVID-19) and 6.6 million deaths have been reported world-wide. Risk factors for severe COVID-19 are known, including those with compromised immunity. Among patients with inborn errors of immunity (IEI), early reports of severe outcomes lead to strict masking and social distancing measures. While this resulted in relatively low infection rates among those with IEI, real-world data describing the clinical course of COVID-19 in this patient population have remained limited. We performed a retrospective study of adult IEI patients followed by our center in which a positive test (rapid antigen or PCR) for COVID-19 was determined between November 2021-November 2022. Medical charts were reviewed, and patient interviews conducted. All patients provided informed consent. Twenty-nine patients were enrolled (22 females, 7 males), aged between 18-69 years (median: 20-29 years). The cohort included those with antibody deficiencies (41.37%), combined immunodeficiencies (34.48%;HIES, CARD11, STAT1-GOF), immune dysregulation disorders (20.69%;LRBA deficiency, AIRE deficiency) and phagocyte defect (3.45%;CGD). The duration of symptoms ranged between 3 days-4 weeks (median: < 1 week). Upper respiratory symptoms (including sore throat, congestion) were reported in 97% while fever was present in 41% of patients. Prior to infection, 14 (48%) patients had underlying asthma or bronchiectasis - 2 subsequently experienced shortness of breath and were treated with inhalers or Sotrovimab, respectively. No treatment was required in 65.5% of cases. The remaining received Paxlovid (10.3%), Sotrovimab (13.79%), or antibiotics (10.3%). Of the 2 patients with STAT1-GOF, one tested positive during a repeat episode of febrile neutropenia which required hospitalization. No other patients were hospitalized or needed ICU admission. No deaths were recorded. In light of these favourable outcomes, patients with IEI can gradually and safely return to normal activities.Copyright © 2023 Elsevier Inc.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Lung Aspergillus niger infection after SARS-CoV2

A 64-year-old never-smoker man, with professional exposure, presented to Marius Nasta Pneumophtisiology Institute for fatigability to effort, in the context of severe SARS-COV2 infection one month previously. His medical history includes pulmonary tuberculosis (55 years ago) and newly diagnosed type II diabetes (261 mg/dL glycemia). The thoracic tomography computer in the immediate post-COVID period (Fig. 1A) revealed the presence of glass ground lesions and a 3 cm nodule with cystic degeneration in the upper left lobe. A gross examination of the specimen identified a condensation area of 2.5 cm diameter, brown-grey colored, with necrosis and central ulceration. Microscopic examination showed the presence of bronchiectasis with squamous metaplasia of the epithelium, which appears ulcerated;numerous calcium oxalate crystals with adjacent foreign body granulomatous reaction;endobronchial are present fibrinous and inflammatory debris, brown-black pigment, and septate, dichotomous branching hyphae, suggestive of Aspergillus spp. A periodic acid-Schiff stain was performed, identifying the fungal hyphae. The histopathological diagnosis was bronchiectasis supra-infected and colonized with fungal filaments (Aspergillus niger).

Mistakes and complications in the diagnosis and treatment of children with organic foreign body aspiration

The reason for the publication of this article was the increase in the number of children with long-standing organic foreign bodies in the respiratory tract, the late diagnosis of which causes severe complications. The article presents the three most significant cases from the general series, when the diagnosis and treatment tactics at the stages of treatment were associated with errors both at the prehospital stage and in the hospital. In the first clinical case, as it turned out, the child had aspired multiple foreign bodies. The first bronchoscopy revealed one solid foreign body. Due to severe fibrinous-purulent endobronchitis and contact bleeding, the bronchoscopy procedure was aborted. However, after 10 days, the child independently coughed up the second seed, which was a surprise to us. Control bronchoscopy after 3 weeks revealed no foreign bodies. In the second clinical observation, a child developed bronchiectasis due to a long stay of a foreign body in the respiratory tract. The third case demonstrates the diagnosis and treatment tactics in a child with a foreign body against the background of a coronavirus infection. In the first and third cases, the results of treatment were satisfactory. In the second case, a long stay of peanuts in the respiratory tract led to bronchiectasis in the lower lobe of the left lung, which required its removal. In the follow-up, there are no complaints, the child grows and develops according to age. The study analyzes the mistakes made at the stages of diagnosis and treatment of children with foreign bodies in the respiratory tract. Conclusion. Young children with long-term and atypically current respiratory diseases, dubious and even normal radiological picture with the absence of comprehensive information on the anamnesis of diseases should alert the doctor to the possibility of aspiration of a foreign body in the respiratory tract and serve as the basis for performing bronchoscopy.Copyright © 2023 National Academy of Pediatric Science and Innovation. All rights reserved.

Incidental findings arising from targeted lung health checks: a GP practice perspective

Introduction: Newcastle Gateshead is a phase one Targeted Lung Health Checks site. Walker Medical Group GP practice serves a deprived population and is a designated Deep End practice. We report on the experience of Targeted Lung Health Checks at this practice. Method(s): Invitations were sent to eligible participants registered at the practice. Lung health checks were carried out by telephone according to Standard Protocol in the context of the COVID 19 pandemic. Those meeting criteria for Low Dose CT were invited to a mobile scanner located in the community near to the practice. Scans were reported according to the Standard Protocol. Result(s): Of 1481 eligible patients, 736 (50.44%) attended a telephone lung health check. 458 (63.6%) met criteria for a CT scan, of whom 33 declined a scan and 2 were unable to lie flat. 11 lung cancers (2.6%) and one other cancer were diagnosed. 71 (16.8%) had nodules requiring follow-up. These cases were managed by the TLHC programme and lung cancer MDT. Incidental findings had the greatest impact on general practice. 72.3% of scans showed coronary artery calcification. Of these, over 1 in 4 was not currently prescribed a Statin. New diagnoses of bronchiectasis (8 patients = 2%) and interstitial lung disease (7 patients = 1.6%) required GP action. 5 new cases of undiagnosed thoracic aortic aneurysm were identified, requiring referral for further action (1%). Conclusion(s): Incidental findings of Targeted Lung Health Checks CT scans require substantial input from a GP team. Coronary artery calcification is numerically most significant. Participants and practices should be supported by information and resources. Thoracic aortic aneurysm cases are also found in significant numbers and TLHC projects are advised to work with cardiology and cardiac surgery units when setting up. We plan to explore the reasons for participant refusal of CT scanning. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.

Real Time Implementation of Robust Sound based Respiratory Disease Classification using Spectrogram and Deep Convolutional Neural Networks

Respiratory diseases become burden to affect health of the people and five lung related diseases namely COPD, Asthma, Tuberculosis, Lower respiratory tract infection and Lung cancer are leading causes of death worldwide. X-ray or CT scan images of lungs of patients are analysed for prediction of any lung related respiratory diseases clinically. Respiratory sounds also can be analysed to diagnose the respiratory illness prevailing among humans. Sound based respiratory disease classification against healthy subjects is done by extracting spectrogram from the respiratory sound signal and Convolutional neural network (CNN) templates are created by applying the extracted features on the layered CNN architecture. Test sound is classified to be associated with respiratory disease or healthy subjects by applying the testing procedure on the test feature frames of spectrogram. Evaluation of the respiratory disease binary classification is performed by considering 80% and 20% of the extracted spectrogram features for training and testing. An automated system is developed to classify the respiratory diseases namely upper respiratory tract infection (URTI), pneumonia, bronchitis, bronchiectasis, and coronary obstructive pulmonary disease (COPD) against healthy subjects from breathing & wheezing sounds. Decision level fusion of spectrogram, Melspectrogram and Gammatone gram features with CNN for modelling & classification is done and the system has deliberated the accuracy of 98%. Combination of Gammatone gram and CNN has provided very good results for binary classification of pulmonary diseases against healthy subjects. This system is realized in real time by using Raspberry Pi hardware and this system provides the validation error of 14%. This automated system would be useful for COVID testing using breathing sounds if respiratory sound database with breathing sound recordings from COVID patients would be available.Copyright © 2023 North Atlantic University Union NAUN. All rights reserved.

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Comparison between in-person and remote assessment of four field tests for people with chronic lung diseases

Introduction: COVID-19 pandemic has driven an abrupt shift from centre-based pulmonary rehabilitation to home-based or telerehabilitation models in order to safely deliver this important treatment. However, functional capacity assessment is still carried out with in-person supervision. Aim(s): To compare remote and in-person assessment of four field tests for patients with chronic lung diseases. Method(s): People with chronic respiratory diseases underwent timed up and go test (TUG), 5-repetitions sit-to-stand test (5-repStS), 1-minute STS (1-minStS), and modified incremental step test (MIST). Tests were carried out at participants' home with in-person or remote (Skype or WhatsApp) assessment, in random order. During the remote assessment, the physiotherapist was at the pulmonary rehabilitation centre. The order of the tests was also randomized and was the same for in-person and remote supervision. Each test was performed twice and the test with best performance was used for comparison between remote and in-person supervision. A kit containing a finger pulse oximeter, tape measure, and a step was provided. Pair t -test expressed as mean difference (95% CI), intraclass correlation coefficient (ICC 2:1), and Bland-Altman method were used for analysis. Result(s): Forty-four participants (23 COPD, 18 bronchiectasis, three cystic fibrosis, FEV 1 47 +/- 19%, 56 +/- 15 years old) were assessed. There was no difference between in-person and remote supervision for all tests (TUG 0.04(-0.2-0.2) s, 5-repStS: 0.3(-0.1-0.7) s, 1-minStS: -0.9 (-1.9-0.1) repetitions, and MIST: -3.1 (-9.9-3.7) steps). High reproducibility was observed by ICC (95% CI) (TUG: 0.94 (0.89-0.97), 5-repStS: 0.96 (0.92-0.98), 1-minStS: 0.87 (0.77-0.93), and MIST: 0.94 (0.88-0.96). Limits of agreement were narrow for TUG (-0.8-1.7), 5-repStS (-2.3-2.9), and 1-minStS (-7.4-5.5), but wide for MIST (-46-40). Conclusion(s): Remote assessment provides similar results to in-person assessment for four field tests commonly used in people with chronic lung diseases.

Telerehabilitation in the 'real-world': Implementation of remotely delivered pulmonary rehabilitation

Introduction: Pulmonary rehabilitation (PR) is an effective treatment for people with chronic respiratory disease but is delivered to <5% of eligible individuals. Home-based telerehabilitation achieves similar clinical outcomes to centre-based PR in clinical trials. We aimed to evaluate the clinical implementation of telerehabilitation. Method(s): Suitable individuals with respiratory disease referred for PR at Alfred Health have been offered the option of an 8-week home-based telerehabilitation program (one home visit followed by twice-weekly exercise training sessions, with real time supervision, for 8-weeks). Equipment was provided to patients, as necessary. Standard PR assessments were conducted pre and post program. Program completion was defined as undertaking >=70% of prescribed sessions. Real-world implementation was evaluated against the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Result(s): Reach: Across 2-years (Sept 2020-22), 269 people were referred with 55 (21%) undertaking telerehabilitation (25 female, mean (SD) age 61 (11) years, 6-min walk distance (6MWD) 430 (120) metres, Chronic Respiratory Questionnaire Dyspnoea (CRQD) domain 16 (6)). Participant diagnoses included COPD (n = 11), ILD (n = 15), bronchiectasis (n = 5), asthma (n = 2), post COVID-19 (n = 9), and pulmonary hypertension (n = 4). Forty participants (73%) completed >=70% of prescribed sessions. Effectiveness: Significant and clinically meaningful improvements were demonstrated (CRQD MD 4 (95% CI 1, 6);6MWD MD 24 m (95% CI 8, 41)). Adoption: Training to deliver telerehabilitation and perform home visits was completed by PR clinicians (n = 7 and n = 4 respectively). Implementation: All participants independently supplied Wi-Fi, and 40% used their own exercise equipment or internet-enabled device. Most participants had an in-person home visit (n = 45), and undertook cycle-based training (n = 46). Fifteen participants required additional support for iPad or videoconferencing navigation. There were no serious adverse advents. Maintenance will be evaluated following this pilot period. Conclusion(s): 'Real-world' telerehabilitation achieves clinically meaningful outcomes for patients and provided access to an effective model of PR particularly when centre-based programs were unavailable due to COVID-19 restrictions.

Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications.

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.

Mistakes and complications in the diagnosis and treatment of children with organic foreign body aspiration.

The reason for the publication of this article was the increase in the number of children with long-standing organic foreign bodies in the respiratory tract, the late diagnosis of which causes severe complications. The article presents the three most significant cases from the general series, when the diagnosis and treatment tactics at the stages of treatment were associated with errors both at the prehospital stage and in the hospital. In the first clinical case, as it turned out, the child had aspired multiple foreign bodies. The first bronchoscopy revealed one solid foreign body. Due to severe fibrinous-purulent endobronchitis and contact bleeding, the bronchoscopy procedure was aborted. However, after 10 days, the child independently coughed up the second seed, which was a surprise to us. Control bronchoscopy after 3 weeks revealed no foreign bodies. In the second clinical observation, a child developed bronchiectasis due to a long stay of a foreign body in the respiratory tract. The third case demonstrates the diagnosis and treatment tactics in a child with a foreign body against the background of a coronavirus infection. In the first and third cases, the results of treatment were satisfactory. In the second case, a long stay of peanuts in the respiratory tract led to bronchiectasis in the lower lobe of the left lung, which required its removal. In the follow-up, there are no complaints, the child grows and develops according to age. The study analyzes the mistakes made at the stages of diagnosis and treatment of children with foreign bodies in the respiratory tract. Conclusion. Young children with long-term and atypically current respiratory diseases, dubious and even normal radiological picture with the absence of comprehensive information on the anamnesis of diseases should alert the doctor to the possibility of aspiration of a foreign body in the respiratory tract and serve as the basis for performing bronchoscopy.Copyright © 2023 National Academy of Pediatric Science and Innovation. All rights reserved.

Lung damage syndromes and extra-respiratory complications at evolutionary stages of SARS-CoV- 2 infection in children

Background: Aim: Study of lung damage syndromes and extra-respiratory complications in children with CoV-2 infection. Method(s): The study included 53children with CoV-2 infection and were evaluated clinically to identify the evolutionary consequences of these diseases. Laboratory tests, pulmonary CT, brain CT, EcoCG were performed. Diagnostic tests to confirm CoV-2: RT PCR-test and/or serological tests for IgM, IgG Ab to CoV-2. Result(s): COVID-19 infection was confirmed by RT PCR test in 79.2%(CI51.7%-78.5%) children, and in 20.8%(CI 10.8%-34.1%) cases by IgM and IgG Ab to SARS-CoV- 2 virus. The mean age of the patients -6.03+/- 5.68. Respiratory manifestations at the COVID-19 stage had of 81.5% children (bronchitis -14.8%, pneumonia -62.9%), and the evolutionary stages were detected pulmonary fibrosis (30.5%), atelectasis (30.5%), bronchiectasis (11.11%). COVID-19- associated neurological syndromes were found in 39.6% of children-migraine headache (9.4%), toxic encephalopathy (7.5%), psychotic disorders (3.8%), neurotic anorexia (1.9%), but also severe neurological complications -multifocal leukoencephalitis(5.7%), acute cerebellitis (3.8%), polyradiculoneuropathy (3.8%), epilepsy (1.9%). Signs of cardiovascular damage were reported in 21.2% of cases:bouts of tachycardia (7.7%), toxic heart disease (5.7%). Children with CHDs (7.7%) had severe heart failure in the post-Covid- 19 stages. Conclusion(s): Clinical manifestations in the evolutionary stages of Covid-19 in children are dominated by impaired respiratory system with signs of pulmonary fibrosis, atelectasis, which are often associated with neurological complications and sometimes with cardiovascular signs.

COVID-19 case series in patients with primary immunodeficiency

Background: There is little information in the literature on primary immunodeficiency (PID) or innate immune error (IEI) as a risk factor for severe COVID-19 disease. Our aim is to detail the course of COVID-19, especially in patients with PID who predominantly have antibody deficiencies. Method(s): In this cross-sectional retrospective study, we included 18 cases (12 males, 6 females) of our 120-patient IEI group, aged between 30 months and 32 years, predominantly with antibody deficiencies. Their mean age was 12.2 (3-32) years. This study retrospectively evaluated IEI patients between February 2020 and February 2022 to determine the prevalence of COVID-19. Assays used: Polymerase chain reaction (PCR) tests from nasopharyngeal swab were positive for SARS-CoV- 2. This study was approved by the Turkish Ministry of Health. Written consent was obtained from all patients or their parents. Sakarya University Ethics Committee was also applied to. Result(s): All of our patients had a benign course, suggesting a possible protective factor related to young age despite IEI. In our patients, there was no other comorbidity other than bronchiectasis in 1 patient. A total of 18/120 (15%) PID patients aged 30 months to 32 years tested positive for SARS-CoV- 2. All patients were on routine monthly IVIG or SCIG replacement therapy at the time of virus detection. In addition, 9/18 patients received intermediate-dose IVIG treatment. Also, 2/18 patients were completely asymptomatic, but 16 out of 18 patients were symptomatic. As a result, none of the patients showed any serious illness, and none even required supplemental oxygen and/or intensive care unit admission. Except for the intermediate dose IVIG treatment, 1 patient was treated with hydroxychloroquine, 1 patient with favipiravir, and 4 patients with ceftriaxone antibiotic treatment. Conclusion(s): If we look at the clinical course and outcome of COVID 19 disease in our patients, all of our patients showed a benign course as well as better results.