key: cord-0797983-s3uja2pq
authors: Yan, Bingdi; Yang, Junling; Xie, Yan; Tang, Xiaolei
title: Relationship between Blood Eosinophil Levels and COVID-19 Mortality
date: 2021-02-11
journal: World Allergy Organ J
DOI: 10.1016/j.waojou.2021.100521
sha: 3e1d244cd34ca45d7146b7a9e4fcff344c3cef2b
doc_id: 797983
cord_uid: s3uja2pq

Objectives A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2, is causing the worldwide coronavirus disease 2019 (COVID-19) outbreak with high mortality. A unique finding among COVID-19 patients was a decline of eosinophil levels (eosinopenia). However, results from previous studies on the relationship between eosinopenia and disease severity were inconsistent. The objective of this study is to determine the relationship between eosinopenia and COVID-19 mortality as well as the clinical conditions that could potentially lead to mortality. Methods One hundred ninety patients diagnosed as moderate, severe, or critical COVID-19 at hospital admission were enrolled. Data collected from patients’ medical records on the second day after hospital admission included medical histories, clinical symptoms, chest images of computed tomography (CT), laboratory examinations, and outcomes. Results Eosinophil levels were significantly lower in patients with critical disease, when compared to those with moderate and severe diseases. After controlled for confounding factors, i.e., age, gender, hypertension, coronary heart disease, diabetes, and chronic lung disease, a progressive decline of eosinophil levels was independently associated with mortality. Moreover, eosinophil levels significantly and positively correlated with platelet and D-dimer levels but significantly and inversely correlated with serum levels of urea, creatinine, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. Conclusions Eosinopenia, if progressively worsening, indicates that COVID-19 patients may progress to critical disease and have a significantly higher chance of mortality. Additionally, eosinopenia correlates with biomarkers of coagulation disorder and those of tissue damage in kidney, liver, and other tissues.

According to the Guidelines for the Diagnosis and Treatment of COVID-19 (5 th 88 version), disease severities were classified as mild, moderate, severe, and critical. In this 89 study, we enrolled patients with moderate, severe, and critical cases, which were judged at All statistical analyses were performed using R-3.6.3 and RStudio Version 1.2.5042.

Continuous variables were assessed for normality of distribution using the Shapiro-Wilk test, 125 with p-value lower than 0.05 as the criterion that a variable deviates from normality.

Independent nominal variables and continuous variables were compared among the three 128 severity levels (moderate, severe, critical) and between the two mortality outcomes (survivors

Eosinophil levels were significantly lower in COVID-19 patients with critical 146 disease, when compared to those with moderate and severe diseases.

We first asked whether eosinopenia was associated with disease severity. We did not Firstly, we found that eosinophil counts and ratios significantly and inversely correlated 199 with infection markers (Fig S1) , i.e., C-reactive protein (CRP), procalcitonin (PRO), and With respect to coagulation disorders, our data showed no significant difference 204 between patients with severe disease and those with moderate disease in the levels of 205 coagulation biomarkers, i.e. prothrombin time (Fig 3A) , fibrinogen degradation products ( Fig   206   3B ), D-dimer (Fig 3C) , fibrinogen (Fig 3D) , and platelet count (Fig 3E) . However, we found 207 that patients with critical disease, when compared to those with severe diseases, showed 208 significantly increased levels of prothrombin time (Fig 3A) , fibrinogen degradation products 209 (Fig 3B) , and D-dimer (Fig 3C) . In contrast, patients with critical disease, when compared to 210 those with severe disease displayed significantly decreased levels of fibrinogen ( Fig 3D) and 211 platelet count (Fig 3E) .

The above observations prompted us to investigate the potential correlation of 214 eosinophil counts and ratios with the above coagulation biomarkers. Our data showed that 215 eosinophil counts and ratios significantly and positively correlated with platelet counts (Fig  3F) , which was consistent with previous reports that eosinophils and platelets interacted with significantly increased serum levels of aspartate aminotransferase (Fig 5A) and alanine 239 aminotransferase (Fig 5B) , indicating liver injury. In addition, patients with critical disease 240 displayed further significantly increased serum levels of aspartate aminotransferase (Fig 5A) 241 but not those of alanine aminotransferase (Fig 5B) , suggesting worsening of liver injury in 242 patients with critical disease. Correlation analyses demonstrated that eosinophil counts and 243 ratios significantly and inversely correlated with serum levels of aspartate aminotransferase 244 (Fig 5C) . Finally, we investigated the effects of eosinopenia on other biomarkers of tissue damage.

Our analyses showed that patients with severe disease, when compared to those with 251 moderate disease, had significantly increased serum levels of lactate dehydrogenase (Fig 6A) 252 but not creatine kinase (Fig 6B) , suggesting tissue damage. In addition, patients with critical 253 disease, when compared to those with moderate and severe diseases, displayed significantly 254 further increase in serum levels of both lactate dehydrogenase (Fig 6A) and creatine kinase 255 (Fig 6B) , suggesting worsening of tissue damage. We did not see significant differences in 256 the serum levels of total amylase among the three disease severities (Fig 6C) . Moreover, our studies demonstrated that a progressive decline of eosinophil levels was 297 associated with mortality among COVID-19 patients (Fig 2) . This finding was also 298 corroborated by other findings in this current study. Firstly, consistent with other reports[15], 299 we found that COVID-19 patients with critical disease had coagulation disorders (Fig 3) . In 300 addition, our analysis revealed a significantly positive correlation of eosinophil counts and 301 ratios with platelet counts (Fig 3) . This finding can be potentially important because previous studies have shown that eosinophils and platelets interact with each other [17] and that 303 eosinophil counts inversely correlated with stroke severity [23] . Secondly, we found that 304 COVID-19 patients with critical disease showed biomarkers of tissue injury (Fig 4, 5, 6) . 305 Importantly, eosinophil counts and ratios significantly and inversely correlated with some of 306 these biomarkers, suggesting that eosinopenia was associated with the organ failure and 307 tissue damage. Hence, our data support the emerging concept that eosinophils promote tissue J o u r n a l P r e -p r o o f

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