Scribd Logo
Upload

Welcome to Scribd!

  • Q. Li - Eosinopenia and Elevated C-Reactive Protein Facilitate Triage of COVID-19 Patients in Fever Clinic - A Retrospective Case-Control Study

    Uploaded by

    Susanyi Ervin
    16 views7 pages

    Original Title

    Q. Li - Eosinopenia and Elevated C-reactive Protein Facilitate Triage of COVID-19 Patients in Fever Clinic_ a Retrospective Case-control Study

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    16 views7 pages

    Q. Li - Eosinopenia and Elevated C-Reactive Protein Facilitate Triage of COVID-19 Patients in Fever Clinic - A Retrospective Case-Control Study

    Uploaded by

    Susanyi Ervin

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 7
    Yee Ty Dec {mG.May 25, 20201521] -cinjateene 000 (2020) 100575 Contents lists available at ScienceDirect EClinicalMedicine Journal homepage: htips:/www journals.elsevier.com/ectinicalmedicine Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: A retrospective case-control study Qilin Li*', Xiuli Ding™', Geqing Xia®', Heng-Gui Chen“, Fenghua Chen*, Zhi Geng*, Luming Xu’, Shijun Lei*, An Pan“, Lin Wang*", Zheng Wang" * parent of il Lara, Resa Center or Tse gineering and Regenerative Med, Union Hes, Tog Medal oles, Hach er sty Sc alec Waa 3002. * apart of ses and Gycaey, Ui lp Tong Medel Cols acho Univer of cece nd Techno, Wh 20022 Chit “Daparnent of Gastritis, earch ene for Tse Eger and egeerte Mein, Union Visi Tog Medal Call zhang Univer of Scene and Teel, Waban 3022, China permet of Edel and ase, Shl of Pac Heal Ter Medial Clege,Hugshong University ofc and Teco, Wao 40030 ARTICLE INFO Agsteact see: Aackrond: Coan dese (COMID9) cased by svete acute repay nome coma 2 fered apt n20 (Sat co) screnys panei affsting over 200 coun. Many Eis Rae bist esate Reve 00 fee clin tage tpectedCOMD-18 pate on ter pens wisn symptoms Howes en sce 2 fo 220 then vali ofthe mc ac ess wel slong malig re fr bth he and raga ‘eraminaton, the quarantine or therapeutic decisions fora large number of mixed patients were offen not ‘made in time. We aimed to identify simple and quicily availabe laboratory biomarkers to facilitate effective fore tage atthe ver cl fr soi sspected COVID 19 patents om thse vith COMI. 19 he symptoms. eon Meteds We oleed cna ctskpeal nd abort dls of 09 pas who sted th Fever Cnc at cosy ‘Wah Uns Hspal Winon Chia fom Jan 31 to fob 21 Based on poleroe cin eacon PER te Ido aa esting flr SARS-COV? ecto, they weve divide nto tee oupe SAIS-COV-2 postive patents as cases and SARS-CoV-2-negatve patients as controls. We compared the clinical features and labo ‘tory finding of the two groups, and analyzed the diagnostic performance of several laboratory parameters In predicting SARS-CoV-2 infection and made relevant comparisons othe Chin diagnosis guideline of hav- ‘nga normal or decreased number of leukocytes (<9 5107/0 mphopenia 11 10"/L. ‘ndings: Normal or decreased number of leukocytes (9-5 1). lymphopenia (<1-1 10), cosinpenia (062 107), and elevated hs-CRP (24 mel.) were presented in 95.0%, 52 2k 74.7% and 86°7% of COVID-1S patients, much higher than 87-22, 2-8% 313% and 45.2% ofthe controls, respectively. The cosinopeia pro- tice a sensivity of 747% and speciicty of G8 7 for separating the two groupe with the aea under the ‘curve (AUC) of 0.717. The combination of eosinopenia and elevated he-CRP yielded a sensitivity of 67 St and specify of 782% (AUC-0'730). The ation ofeosinopena alone or the combination of esinopenia and evated is-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predic- tive capacity with higher than zero ofboth net reclassification improvement (NR) and integrated sein tion improvement 1D). Interpretation: The combination of cosinopeia and elevated hs-CRP can effectively triage suspected COVID- 19 patients fom ether patients attending te fever elinic with COVID-10-thke inal symptoms. This fining would be particulary useful for designing triage strategies in an epidemic region having a large number of patents with COVID-19 and other respiratory diseases while limited medical resources for nucle aod tests and radiographic examination. "© 2020 The Authors Published by BsevierLtd-This is an open access article under the CCBY-NCND license (htp:/ereativecommonscogyicenses)oy-ne-nd/40)) uding This work was supprted by the Nationa Natural Science Foundation of Chin (NSF) andthe Major Scenic and Technol Innovation Projets of Hubei Previce sm) * Conesponding authors ‘Erma dienes ponanst tac (A Pe) "These authors corte exalt ke segs eden Wang) shengwang@hist ten (2 Wan) ‘wap o.og/101046)ctnm 2020100375. 2540-53701 200 The Authors. Pubs by Evie id, Thisis an open access rie under the CC NC-ND ese (i aeatiecomsonsonicnssy nc d/40)) TS SnD ECLINM 2 tera ected 0 (2020) 10375 Research in context ‘A key t0 slow the spread towards outbreak containment is rapid Evidence before tis study diagnosis and isolation of cases [7]. This relies on effective triage pro- ‘As of April 3, 2020, the outbreak of 2019 novel coronavirus (COVID-19) has led to 972,303 confirmed cases with $0,322 deaths globally. In Wuhan, a large mumber of mixed patients of| ‘rue or suspected COVID-19 cases and those with other pneu- 'monia or respiratory infections swarmed into designated fever clinics. This brought tremendous pressure on patient triage at fever clinics. However, most of published COVID-19 papers facused on clinical characteristics of hospitalized patients but ‘not COVID-19 outpatients. We searched PubMed for studies related to the biomarkers for effective triage of COVID-I9 clinics up to April 3, 2020. The search terms included “triage” “prediction”, "biomarker", and “COVID-19", and yield no rele- vant papers. ‘Added value ofthis study “To the best of our knowledge, this isthe Mrs retrospective anal- ysis focused on how to improve triage process during COVID-19 outbreak at fever clinics. We compared laboratory findings between laboratory-confirmed SARS-CoV-2-positive patients and SARS-CoV-2-negative patients, both of which presented similar fever and respiratory symproms. Differentiating these {wo types of patients was a core question to be solved during triage at fever clinics. Our study revealed that eosinopenia and elevated high-sensitivity C-reactive protein (hs-CRP) level were ‘observed in the majority of SARS-CoV-2-positive patients, and the combination of eosinopenia and elevated hs-CRP was capa- ble of predicting true COVID-19 patients (72.8% positive predic- tion) more efficiently than the combination of “normal or decreased numberof leukocytes" andjor “lymphopenia” (48.4% positive prediction, two diagnostic parameters recommended by the Guideline of the China National Health Committee for COVID-19 diagnosis (6th edition). Implications of al the available evidence osinopenia along with increased hs-CRP can be used to rapidly and effectively triage suspected cases from mixed patients with Similar COVID-19-telated symptoms at fever clinics. These patients should be priartized for computerized tomography (Ct) diagnostic examination and COVID-19 nucleic acid poly ‘merase chain reaction (PCR) testing when resources are limited. (ur finding may provide useful information for designing ‘proper triage strategies in regions, which have begun to strug gle with COVID-19 outbreak or might have similarly intense COviD-19 local outbreak inthe fucue. 1. Introduction AAs of April 3, 2020, laboratory-confirmed severe acute respiratory ‘syndrome coronavirus 2 (SARS-CoV-2) infection across China has reached over 80,000 cases |]. The WHO named this coronavirus dis- cease as COVID-19 and declared it as a public health emergency of international concern (2). COVID-19 has now affected over 200 cou- ties and terttories [3-5], and a surge in cases (972.303 confirmed ‘cases with 50,322 deaths globally) has been noted in multiple coun- tries outside of China, including the United States, tay, Spain, Ger- ‘many, France, iran, the United Kingdom, japan, and South Korea 5]. Such an urgent situation underscores the importance of effec- tively identifying infeeted patients for timely treatment in relevant ‘epidemic regions. tocos identifying suspected patients for isolation or further diagnos- tic examination towards timely treatment [8,9]. By referring to previous experience of combatting SARS-CoV in 2003 in China, desig- hated fever clinics were quickly established across epidemic regions to triage suspected patients, COVID-19-Lke initial symptoms include fever and respiratory symptoms (such as dry cough and shortness of breath) (10). These symptoms are however not specific, and realy ‘confused with other non-bacterial community-acquited pneumonia ‘or common upper respiratory infection, Thus, a critical task of triage at the fever clinic was how to accurately and effectively sort sus- pected COVID-19 patients from chose of other pneumonia or respira- tory infection who presented with COVID-19-lke symptoms. ‘This triage was particularly challenging because immediately after ‘the COVID-19 outbreak, an overwhelmingly large number of mixed patients with fever or respiratory symptoms flooded in, resulting in long waiting time for computerized tomography (CI) examination and ctiolozical polymerase chain reaction (PCR) tests. This signifi- ‘cantly delayed diagnosis and subsequent quarantine or therapeutic ‘decisions. Due to these reasons, many true COVID-19 patients were left un-diagnosed at fever clinies causing cross infection, or were sel isolated at home, which was however often ineffective and could lead to family cluster infections and poor prognosis because of delayed treatment. Therefore, it is highly desired to develop more ‘effective ways of optimizing the triage process at fever clinics to sort suspected COVID-19 patients out of patients with similar symptoms ‘Those suspected COVID-19 patients would be prioritized for diagnos- tie CT examination and etiological PCR tests. Thus, we set co identify simple and quickly available laboratory parameters as biomarkers for precise and effective triage. 2. Methods 2.1, Patents Data of this retrospective case-control study were consecutively ‘collected from 3323 patients who made first medical vist at the Fever linc of Wuhan Union Hospital from Jan 31 to Feb 21, 2020, prior to any antiviral and anti-bacterial treatments that they might receive later on. The majority ofthe patients presented fever andjorrespira- tory symptoms at the fever clinic. We excluded patients without blood routine examinations (n = 1749) mainly because these patients (1) had already received blood routine examination in community clinics and ther blood testing results were not obrainable, (2) were transferred 10 designated hospitals for isolation and treatment, or (3) made their ‘own decisions to refuse Further routine blood tests or goto ather hos Pitals for further testing and treatment. We also exciuded patients ‘who already had CT examination and were considered as suspected COVID-19 cases (n = 151), those with unknown status of SARS-CoV-2 infection n= 329), and those with irrelevant symptoms oF conditions (n= 105), Finally, a total of 989 patients were included forthe analyses (Fig. 1). All patients’ throat swab specimens were subject to nucleic acid testing for SARS-CoV-2, Among, them, 458 patients were tested Positive and considered as COVID-19 cases and 531 were tested nega- tive and considered. as controls. Two researchers independently ‘extracted and reviewed the data. This study was approved by the ‘Wuhan Union Hospital Ethics Committee. 22, Procedures Etiological examination, blood routine analysis, and high-sensiiv- ity C-reactive protein (hs-CRP) quantification were performed in clin- ical laboratory of Wuhan Union Hospital. Blood biomarker tests were Yee Ty Dec oT (eta eamkatodane 0 2020) 100375 {mG.May 25, 20201521] avid tom an oF 21.2020 3323 oupatnts aleve Ce iestedTor SARS ¥ 1574 nckceain lowing area Be exceed 1329 ambiguous PCR outomes 151 incomplete corse of cincal formation 105 rewvart ‘98 reguiarmescal examinations FS anaitaire 1 eacoeythemia ‘heey 1 diabetes eyelceyet ¥ ‘See nencesin he wy 1458 beratory-contmes COVD-19 35 but less than 38 for two times) was defined as postive. 23, Definitions ‘The WHO interim guidance for COVID-19" defines suspected ‘cases that should meet two criteria: (1) clinical features: respiratory- infection symptoms that cannot be fully explained by other etiology: and (2) epidemiological features (affected geographic regions travel history or close contact with a confirmed or probable case. In the WHO interim guidance, the laboratory evidence was not required t0 define a suspected case. In addition to WHO guideline, different countries can have their own guidelines. In China, the Guidelines of the National Health Commission of China for COVID-19 (6th edition) [12] was followed during this study. According to it, suspected CCOVID-19 cases would have the following features: (1) recent travel history to Wuhan Gty oF Hubei Province or close contact with a con- firmed or probable case; (2) fever and) or respiratory symptoms; (3) laboratory findings of normal or decreased number of leukocytes and] or lymphopenia; (4) radiographic evidence showing pneumonia, ‘The suspected cases were defined if they met the following criteria: (1) plus any two of (243\, oF three of (2)3)(4) at the same time. For simplicity, the two parameters (normal or deereased number of Teukocytes andjor lymphopenia) described in “(3° were referred to as one term “Guideline” forthe following analyses. russes: PO, polymerase hain reaction 2A. Statistical analysis Biomarkers from blood routine examination were dichotomized according to normal reference range used in clinics. Characteristics of laboratory-confirmed SARS-CoV-2-positive and SARS-CaV2-nega- tive patients were compared using Mann-Whitney U tests or chi square tests where appropriate. Univariate logistic models were established to examine risk factors for COVID-19. Those showing sig- nificant associations were further included in the multivariable logis- tic analysis. ‘Significant biomarkers both in the aforementioned univariate and ‘multivariable logistic analyses were then used to construct the pre- diction models. The diagnostic performance of each prediction model ‘was evaluated using sensitivity, specificity, postive predictive value (PPV), negative predictive value (NPV), Youden index (YI) [13], And consistency rate (CR). The improvement in discrimination ‘was assessed by comparing the area under the curve (AUC) of receiver operating characteristic (ROC) between the “Guideline” and the model plus the biomarkers identified from the above analyses [14]. Net reclassification improvement (NRL. the improvement in classification probabilities) and integrated dis- crimination improvement (IDI, the improvement in discrimina- tion) statisties were also utlized as supplementary approaches to assess the incremental improvement in prediction over the exist- ing *Guideline™ [15.10]. In addition, Akaike information criteria (AIC) was used to assess the goodness of fit of all models, with lower AICs indicating better model fit. ‘Among 531 patients who were tested negative forthe SARS-CoV- 2 infection, 95 had two or more nucleic acid tests that were all neza- tive. Thus, we used these 95 patients as the controls in a sensitivity analysis given that they were most unlikely true COVID-19 patients Since we dic not have a validation cohort and ur selected model ‘ight be subject to overfitting, a 10-fold cross-validation method (9 training datasets and 1 validation dataset) was utilized to evaluate the goodness-oF fit of the model identified from the above analyses [17]. To evaluate the influence of missing values forthe hs-CRP, a sen- sitivity analysis of excluding those with missing data was performed. ‘A 2etaled p value <005 was considered as statistically significant. Leesa SnD ECLINM [msGiMay 2, 2020-132] 4 era ecntnetce 02020) 100375 (Eos and bs-CRP) and Leu ROC area: 0.723 ig. 2. ROC curves of single ar combined ol biomarkers on difeetating patients wth COMI-19(n = 458) ram the conto = 531). COVD- 18 eros disease: as csinopeni: CRP, ih-srsitty Creative protein nese Lu: noma deceased number of eukecytes: ROC eee operating characteristic ‘able Comparison ofthe dagstic perfomance btwoon the Guideline parameters andthe Guideline parameters pls Es (Eos and hs CRP) (n= 960) Trssion dee Sensiviy (9) Speceiy() PPVEH NEVIR) WIG ORR) AIC AUC Nal ey (<9 5) andoriym (11) ered ws we 02, wt Gta 80 50s 13109 oswlOs% 05H “Caieine) ailing oe( 002), ma no 5 74 M1 TO 11614 0731107030755) 0868 0175 Gaitine (6s 002 and CRP 40) s9 732 Bs _ 733 _%61_T3A_11330 074510718 0772) 0821 0202 ‘Tee units mE orkstRP. and 10 Lev. ym and Eos. [NIC Alaie information rea: AU re under the cave: CR, consistency ae xs: eosiopena h-

    You might also like