Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Eosinopenia <100/µL as a marker of active COVID-19: An observational prospective study.

OBJECTIVES: To analyse the diagnostic performance of eosinopenia, alone or combined with polymorphonuclear neutrophils (PMN) and/or lymphocytes, as a marker of active COVID-19 in patients hospitalized for suspicion of SARS-CoV-2 infection. METHODS: A prospective observational study including patients hospitalized for suspicion of COVID-19 in a COVID unit was performed from 20th March to 5th April 2020, in Perpignan, France. Patients for which there was a doubt upon diagnosis, who were recently under oral corticosteroids, had myeloid malignancy or human immunodeficient virus infection were excluded. SARS-CoV-2 detection was performed using an RT-PCR assay, from nasopharyngeal swab specimens. Complete blood count were performed for all patients. RESULTS: One-hundred and twenty-one patient were included: 57 patients were diagnosed with COVID-19, 64 patients were not. Eosinophil count was lower in the COVID-19 group (median: 0/µL versus 70/µL, p < 0.0001). To diagnose COVID-19, eosinopenia had a sensitivity of 89.5% and a specificity of 78.1% while lymphopenia's were 73.7% and 62.5% respectively. Using area under curve (AUC) of receiving operating characteristics (ROC) curves, eosinophil's optimal cut-off level was 10/µL, sensitivity and specificity were 86%, and 79.7% respectively. Regarding the eosinophil/PMN ratio, the optimal cut-off level was 3.344, sensitivity and specificity were 87.7% and 73.4% respectively. The AUC of lymphocyte/PMN ratio was significantly lower than eosinophil/PMN ratio's (0.621 versus 0.846, p = 0.0003). CONCLUSION: Eosinopenia - <10/µL - and eosinophil/PMN ratio are useful, low-cost, reproducible tools to help diagnose COVID-19, during an epidemic period, in a population of hospitalized patients admitted for suspicion of COVID-19.

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids.

Eosinophils are important effector cells involved in allergic inflammation. When stimulated, eosinophils release a variety of mediators initiating, propagating, and maintaining local inflammation. Both, the activity and concentration of secreted and cytosolic phospholipases (PLAs) are increased in allergic inflammation, promoting the cleavage of phospholipids and thus the production of reactive lipid mediators. Eosinophils express high levels of secreted phospholipase A2 compared to other leukocytes, indicating their direct involvement in the production of lipid mediators during allergic inflammation. On the other side, eosinophils have also been recognized as crucial mediators with regulatory and homeostatic roles in local immunity and repair. Thus, targeting the complex network of lipid mediators offer a unique opportunity to target the over-activation and 'pro-inflammatory' phenotype of eosinophils without compromising the survival and functions of tissue-resident and homeostatic eosinophils. Here we provide a comprehensive overview of the critical role of phospholipase-derived lipid mediators in modulating eosinophil activity in health and disease. We focus on lysophospholipids, polyunsaturated fatty acids, and eicosanoids with exciting new perspectives for future drug development.

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.

Clinical features of patients with coronavirus disease 2019 from a designated hospital in Beijing, China.

Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19.

Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype.

BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.

SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns.

"Severe acute respiratory syndrome" (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.

Laboratory findings of COVID-19: a systematic review and meta-analysis.

The Coronavirus Disease (COVID-19) pandemic first broke out in December 2019 in Wuhan, China, and has now spread worldwide. Laboratory findings have been only partially described in some observational studies. To date, more comprehensive systematic reviews of laboratory findings on COVID-19 are missing. We performed a systematic review with a meta-analysis to assess laboratory findings in patients with COVID-19. Observational studies from three databases were selected. We calculated pooled proportions and 95% confidence interval (95% CI) using the random-effects model meta-analysis. A total of 1106 articles were identified from PubMed, Web of Science, CNKI (China), and other sources. After screening, 28 and 7 studies were selected for a systematic review and a meta-analysis, respectively. Of the 4,663 patients included, the most prevalent laboratory finding was increased C-reactive protein (CRP; 73.6%, 95% CI 65.0-81.3%), followed by decreased albumin (62.9%, 95% CI 28.3-91.2%), increased erythrocyte sedimentation rate (61.2%, 95% CI 41.3-81.0%), decreased eosinophils (58.4%, 95% CI 46.5-69.8%), increased interleukin-6 (53.1%, 95% CI 36.0-70.0%), lymphopenia (47.9%, 95% CI 41.6-54.9%), and increased lactate dehydrogenase (LDH; 46.2%, 95% CI 37.9-54.7%). A meta-analysis of seven studies with 1905 patients showed that increased CRP (OR 3.0, 95% CI: 2.1-4.4), lymphopenia (OR 4.5, 95% CI: 3.3-6.0), and increased LDH (OR 6.7, 95% CI: 2.4-18.9) were significantly associated with severity. These results demonstrated that more attention is warranted when interpreting laboratory findings in patients with COVID-19. Patients with elevated CRP levels, lymphopenia, or elevated LDH require proper management and, if necessary, transfer to the intensive care unit.