Persons Diagnosed with COVID in England in the Clinical Practice Research Datalink (CPRD): A Cohort Description (preprint)

Objective: To create case definitions for confirmed COVID diagnoses, COVID vaccination status, and three separate definitions of high risk of severe COVID, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID epidemiology in England. Design: Retrospective cohort study Setting: Electronic healthcare records from primary care (Clinical Practice Research Datalink, or CPRD) linked to secondary care data (Hospital Episode Statistics, or HES) data covering 24% of the population in England Participants: 2,271,072 persons aged 1 year and older diagnosed with COVID in CPRD Aurum between August 1, 2020 through January 31, 2022. Main Outcome Measures: Age, sex, and regional distribution of COVID cases and COVID vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalized for COVID (primary diagnosis code of ICD-10 U07.1 COVID-19). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the United Kingdom (NHS Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritization for vaccination). Results: Compared to national estimates, CPRD case estimates underrepresented older adults in both the primary care (age 65-84: 6% in CPRD vs 9% nationally) and hospitalized (31% vs 40%) cohorts, and overrepresented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East, vs 15% nationally). The majority of non-hospitalized cases and all hospitalized cases had not completed primary series vaccination. In primary care, persons meeting high risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score. Conclusions: CPRD primary care data is a robust real-world data source and can be used for some COVID research questions, however limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28,000 codes to define each of three definitions of high risk of severe disease.

Acute exacerbation of idiopathic hypereosinophilic syndrome following asymptomatic coronavirus disease 2019: a case report.

BACKGROUND: Previous research has suggested that some autoimmune diseases develop after the occurrence of coronavirus disease 2019. Hypereosinophilic syndrome is a rare disease presenting with idiopathic eosinophilia and multiple organ involvement, including the skin, lungs, gastrointestinal tract, heart, and nervous system. The diagnosis of idiopathic hypereosinophilic syndrome poses a dilemma because clinical manifestation and serum biomarkers are similar to those of eosinophilic granulomatosis with polyangiitis. Only a few cases have been reported where coronavirus disease 2019 may have caused the new onset or exacerbation of eosinophilic granulomatosis with polyangiitis or idiopathic hypereosinophilic syndrome. CASE PRESENTATION: We present the case of a 48-year-old Japanese woman with history of asthma who developed deteriorating symptoms of insidiously developed idiopathic hypereosinophilic syndrome following asymptomatic coronavirus disease 2019. She developed acute-onset back pain, tachycardia, abdominal discomfort, loss of appetite, weight loss, skin rash on the back, and numbness of the extremities 3 days after the quarantine period. Extreme hypereosinophilia with multiple abnormal findings including pulmonary ground-glass opacity lesions and mononeuritis multiplex was consistent with hypereosinophilic syndrome. Normal cellularity with eosinophilic proliferation in the bone marrow and negative FIP1L1-PDGFRA raised the diagnosis of idiopathic hypereosinophilic syndrome. Although the patient tested negative for anti-neutrophilic cytoplasmic antibodies and skin biopsy was negative for vasculitis, eosinophilic granulomatosis with polyangiitis could not be excluded. Since glucocorticoids are a standard therapy for both idiopathic hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis, we initiated glucocorticoids following a multidisciplinary discussion. CONCLUSION: Although the relationship between asymptomatic coronavirus disease 2019 and acute idiopathic hypereosinophilic syndrome exacerbation was uncertain, the chronological order of the symptomatic development suggested a possible link. More clinical cases and population-based studies are needed to determine the potential effect of coronavirus disease 2019 on autoimmune diseases.

Hyper-eosinophilic syndrome with myocarditis after inactivated SARS-CoV-2 vaccination: A case study (preprint)

A young man without any co-morbidities presented with persistent periorbital baggy swelling along with itchy swelling over fingers, resting tachycardia and exertional breathlessness following first dose of an inactivated SARS-CoV-2 vaccination (COVAXIN). On investigation, patient had elevated blood eosinophils and myocarditis. He was successfully treated with steroid and supportive treatment.

Transient left ventricular clot in COVID-19-related myocarditis is associated with hypereosinophilic syndrome: a case report.

Frequent clinical presentations have been reported in patients with Coronavirus disease 2019 (COVID-19). It may be associated with multi-organ and cardiovascular involvements such as myocarditis and clot formation. Hypereosinophilic syndrome (HES) is a rare disease diagnosed with idiopathic eosinophilia and organ involvement. Here, we report a patient with COVID-19 who presented with clot formation and myocarditis. One month after discharge, regarding persistent peripheral/bone marrow hypereosinophilia and clot in echocardiography, fluorescent in situ hybridization (FISH) analysis was done that showed FIP1L1-CHIC2 fusion (PDGFRɑ rearrangement) in 18% of scored cells and PDGFRß rearrangement in 12% of scored cells, which confirmed HES diagnosis. Clot formation may be a late manifestation of COVID-19 or myocarditis due to COVID-19, or the first manifestation of HES that COVID-19 might provoke in this rare syndrome.

Peripheral Blood Examination Findings in SARS-CoV-2 Infection in Pediatric Patients (preprint)

Background: The findings of peripheral blood examination (PBE) in SARS-CoV2 infection in pediatrics patients have not been fully described, the reports have been done on the adult population so far. In this study we showed the characteristics in the PBE in SARS-CoV2 infection in the pediatric population. Methods Descriptive, observational, longitudinal, prospective study. Information from the medical records of pediatric patients < 17 years of age with a diagnosis of SARS-COV-2 (positive PCR test) was analyzed and peripheral blood smear examination was performed. Results 16 pediatric patients with a diagnosis of SARS-CoV-2 /COVID-19 were evaluated. 100% of the patients had PBE done, 62.50% (10/16) had no morphological alteration of the erythroid cell line, the erythroid changes were: anisocytosis and echinocytosis in 12.5% (2/16), in white cell line a predominance of plasmacyte lymphocytes was found in 37.5% (6/16), followed by hyposegmented neutrophils “Pelger-Huet anomaly” 31.25% (5/16), hypersegmented neutrophils 12.5% (2/16) , atypical lymphocytes 18.75% (3/16), granular lymphocytes in 6.25% (1/16), prolymphocytes in 6.25% (1/16), hyposegmented eosinophils in 12.5% (2/16). Conclusion Plasmacytoid lymphocytes and large granular lymphocyte are seen more frequently in pediatric patients with COVID-19. Abnormalities in the neutrophils with acquired Pelger-Huët anomaly (APHA) were important findings in pediatric patients with COVID-19.

Hypereosinophilic syndrome with multiorgan involvement: an interdisciplinary work-up.

A previously healthy 40-year-old man was referred to our emergency department with pruritic skin lesions and dyspnoea. Laboratory investigation revealed hypereosinophilia. Further diagnostic work-up confirmed the diagnosis of idiopathic hypereosinophilic syndrome (iHES), a rare myeloproliferative disease with a heterogeneous clinical presentation. We describe a unique case with cardiac, pulmonary, hepatic and cutaneous involvement at time of presentation. This case accentuates the importance of an extensive multidisciplinary diagnostic work-up, since iHES is a condition with potential rapid progressive multiorgan failure which requires prompt analysis and treatment. In addition, this case emphasises the importance of being aware of tunnel vision, especially during the COVID-19 pandemic, which might give rise to an increased risk of missing rare diagnoses. Our patient was treated with prednisolone, after which both his clinical condition and eosinophil concentrations markedly improved.

Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma (preprint)

Background: Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Two Immunocompromised Patients With Diffuse Alveolar Hemorrhage as a Complication of Severe Coronavirus Disease 2019.

Diffuse alveolar hemorrhage (DAH) is a severe and potentially life-threatening disease manifestation. In addition to autoimmune diseases such as antineutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane syndrome, pulmonary viral infections are known to be culprits of DAH. Health-care providers worldwide in the coronavirus disease 2019 pandemic have been confronted with an unprecedented number of viral lung infections, with great variance in symptoms and severity. Hemoptysis, the key symptom of DAH, is a rare complication. We present two cases of immunocompromised patients with rapidly developing hypoxemic respiratory failure and evidence of DAH in the context of severe acute respiratory syndrome coronavirus 2 infection.