Eosinopenia is a reliable marker of severe disease and unfavourable outcome in patients with COVID‐19 pneumonia

Cazzaniga, M.; Fumagalli, Luca; D'Angelo, L.; Cerino, Mario; Giulia, Bonfanti; Fumagalli, Riccardo M.; Schiavo, Gianpaolo; Lorini, Cristina; Lainu, Elisa; Terragni, Sabina; Chiarelli, Marco; Scarazzati, Claudio; Bonato, Claudio; Zago, Mauro

doi:10.1111/ijcp.14047

Cited by 37 publications

(41 citation statements)

References 11 publications

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“…Another potential explanation for an association between diphenhydramine and an increased likelihood of testing negative for SARS-CoV-2 is that allergies themselves, rather than the medication used to treat them, might be protective against SARS-CoV-2 infection. [30,31] However, in our study, allergies as documented in the EHR were not significantly associated with an increased likelihood of testing negative. Future studies of populations where testing is routine, systematic, and obligatory, such as certain geographically-isolated college campuses with universal, frequent testing, [32] might reduce the impact of the selection biases highlighted in this study and provide a better opportunity to measure possible protective effects of medications on the development of SARS-CoV-2 infection.…”

Section: Discussioncontrasting

confidence: 75%

The influence of selection bias on identifying an association between allergy medication use and SARS-CoV-2 infection

Thompson¹,

Gurka²,

Filipp³

et al. 2021

eClinicalMedicine

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Background: Medications to prevent and treat SARS-CoV-2 infection are needed to complement emerging vaccinations. Recent in vitro and electronic health record (EHR) studies suggested that certain allergy medications could prevent SARS-CoV-2 infection. We sought to carefully examine the potential selection bias associated with utilizing EHRs in these settings. Methods: We analyzed associations of three allergy medications (cetirizine, diphenhydramine or hydroxyzine) with testing negative for SARS-CoV-2, measuring the potential effect of selection bias on these associations. We used a retrospective cohort of EHR data from 230,376 patients (18 years+) who visited outpatient clinicians in a single, large academic center at least once but were never hospitalized (10/1/2019À6/1/2020). Main exposures included EHR documentation of three allergy medications and allergy, with an intermediate outcome of receipt of a SARS-CoV-2 test, and the primary outcome as testing negative. Findings: SARS-CoV-2 testing rates varied by sex, age, race/ethnicity and insurance. Increasing age and public insurance were associated with a higher adjusted odds of test negativity, while being Black or Hispanic was significantly associated with test positivity. Allergy diagnosis and use of any of three allergy medications were each associated with a higher likelihood of receiving a test (e.g. diphenhydramine -Odds Ratio (OR) 2.99, 95% Confidence Interval (CI) 2.73, 3.28; cetirizine 1.75 (95% CI 1.60, 1.92)). Among those tested, only use of diphenhydramine was associated with a negative SARS-CoV-2 test (adjusted OR = 2.23, 95% CI 1.10, 4.55). However, analyses revealed that selection bias may be responsible for the apparent protective effect of diphenhydramine. Interpretation: Diphenhydramine use was associated with more SARS-CoV-2 testing and subsequent higher odds for negative tests. While EHR-based observational studies can inform a need for interventional trials, this study revealed limitations of EHR data. The finding that diphenhydramine documentation conferred a higher odds of testing negative for SARS-CoV-2 must be interpreted with caution due to probable selection bias.

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Section: Discussioncontrasting

confidence: 75%

The influence of selection bias on identifying an association between allergy medication use and SARS-CoV-2 infection

Thompson¹,

Gurka²,

Filipp³

et al. 2021

eClinicalMedicine

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show abstract

“…Eotaxin has the potential to act as a marker to predict disease severity and outcome. Although it is seen to progressively elevate in patients with mild symptoms, eosinopenia has been detected in patients with severe disease with a subsequent increase being associated with a good outcome [ 93 , 94 , 95 ]. AGP is an acute‐phase protein, and plasma levels of AGP have previously been found to be correlated with influenza disease progression and could be a potential novel biomarker for SARS‐CoV‐2 disease progression [ 96 ].…”

Section: Resultsmentioning

confidence: 99%

Genome‐scale metabolic modelling of SARS‐CoV‐2 in cancer cells reveals an increased shift to glycolytic energy production

et al. 2021

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Cancer is considered a high‐risk condition for severe illness resulting from COVID‐19. The interaction between severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and human metabolism is key to elucidating the risk posed by COVID‐19 for cancer patients and identifying effective treatments, yet it is largely uncharacterised on a mechanistic level. We present a genome‐scale map of short‐term metabolic alterations triggered by SARS‐CoV‐2 infection of cancer cells. Through transcriptomic‐ and proteomic‐informed genome‐scale metabolic modelling, we characterise the role of RNA and fatty acid biosynthesis in conjunction with a rewiring in energy production pathways and enhanced cytokine secretion. These findings link together complementary aspects of viral invasion of cancer cells, while providing mechanistic insights that can inform the development of treatment strategies.

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“…Eosinophils additionally show hepatoprotective activity [14] and cardiac protective function after myocardial infarction [15]. Of particular interest, a robust inverse correlation between eosinophil numbers and severity of novel coronavirus disease of 2019 (COVID- 19) infection was observed [16][17][18][19][20]. Furthermore pre-existing eosinophilia in asthmatics was proven to be protective against COVID-19-associated hospital admission, while development of eosinophilia during hospitalization was associated with decreased mortality [21].…”

Section: Introductionmentioning

confidence: 99%

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

Knuplez

Sturm

Marsche

2021

IJMS

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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.

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Eosinopenia is a reliable marker of severe disease and unfavourable outcome in patients with COVID‐19 pneumonia

Cited by 37 publications

References 11 publications

The influence of selection bias on identifying an association between allergy medication use and SARS-CoV-2 infection

The influence of selection bias on identifying an association between allergy medication use and SARS-CoV-2 infection

Genome‐scale metabolic modelling of SARS‐CoV‐2 in cancer cells reveals an increased shift to glycolytic energy production

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

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