{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T13:35:28Z","timestamp":1680528928327},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation &amp;lt;92%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46\u00b12.64 vs 22.62\u00b13.37, p=0.0001; AL, RC vs not: 531.49\u00b1289.09 vs 764.69\u00b1481.79, p=0.0001; NLR, RC vs not: 3.42\u00b10.75 vs 2.59\u00b10.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct &amp;lt;19.9, AL &amp;lt;630.8\u00d7103\/\u03bcL and NLR &amp;gt;3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/trstmh\/trab182","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:12:32Z","timestamp":1637093552000},"page":"628-635","source":"Crossref","is-referenced-by-count":2,"title":["Combination of cycle threshold time, absolute lymphocyte count and neutrophil:lymphocyte ratio is predictive of hypoxia in patients with SARS-CoV-2 infection"],"prefix":"10.1093","volume":"116","author":[{"given":"Visula","family":"Abeysuriya","sequence":"first","affiliation":[{"name":"Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suranjith L","family":"Seneviratne","sequence":"additional","affiliation":[{"name":"Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals PLC , Colombo, Sri Lanka"},{"name":"Institute of Immunity and Transplantation, Royal Free Hospital and University College London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjuna P","family":"de Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of Kelaniya , Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riaz","family":"Mowjood","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shazli","family":"Mowjood","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thushara","family":"de Silva","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Primesh","family":"de Mel","sequence":"additional","affiliation":[{"name":"Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandima","family":"de Mel","sequence":"additional","affiliation":[{"name":"Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lal","family":"Chandrasena","sequence":"additional","affiliation":[{"name":"Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals PLC , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R S","family":"Wijesinha","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital, Princess Alexandra Hospital NHS Trust , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amitha","family":"Fernando","sequence":"additional","affiliation":[{"name":"National Hospital , Colombo, Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"de Mel","sequence":"additional","affiliation":[{"name":"Department of Haematology-Oncology, National University Cancer Institute, National University Health System Singapore , Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"2022070621365120000_bib1","volume-title":"Rolling updates on coronavirus (COVID-19). WHO characterizes COVID-19 as a pandemic, 2019\u201320","author":"World Health Organization"},{"issue":"3","key":"2022070621365120000_bib2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4236\/aid.2020.103014","article-title":"Atypical presentations of COVID-19","volume":"10","author":"Jayasekara","year":"2020","journal-title":"Adv Infect Dis"},{"key":"2022070621365120000_bib3","doi-asserted-by":"crossref","first-page":"205031212095792","DOI":"10.1177\/2050312120957925","article-title":"Neurological manifestations in COVID-19: a narrative review","volume":"8","author":"Rahman","year":"2020","journal-title":"SAGE Open Med"},{"key":"2022070621365120000_bib4","doi-asserted-by":"crossref","DOI":"10.1093\/trstmh\/trab042","article-title":"Gastrointestinal manifestations in COVID-19","author":"Kariyawasam","year":"2021","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2022070621365120000_bib5","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13054-020-02911-9","article-title":"Acute respiratory failure in COVID-19: is it \u201ctypical\u201d ARDS?","volume":"24","author":"Li","year":"2020","journal-title":"Crit Care"},{"issue":"4","key":"2022070621365120000_bib6","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s11033-021-06358-1","article-title":"Silent hypoxia in COVID-19: pathomechanism and possible management strategy","volume":"48","author":"Rahman","year":"2021","journal-title":"Mol Biol Rep"},{"key":"2022070621365120000_bib7","first-page":"507","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume-title":"Lancet","author":"Chen","year":"2020"},{"issue":"11","key":"2022070621365120000_bib8","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"issue":"18","key":"2022070621365120000_bib9","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N Engl J Med"},{"key":"2022070621365120000_bib10","doi-asserted-by":"crossref","first-page":"m606","DOI":"10.1136\/bmj.m606","article-title":"Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series","volume":"368","author":"Xu","year":"2020","journal-title":"BMJ"},{"key":"2022070621365120000_bib11","volume-title":"Provisional clinical practice guidelines on COVID-19 suspected and confirmed cases","author":"Ministry of Health Sri Lanka","year":"2020"},{"key":"2022070621365120000_bib12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cytogfr.2020.06.001","article-title":"SARS-CoV-2 infection: the role of cytokines in COVID-19 disease","volume":"54","author":"Costela-Ruiz","year":"2020","journal-title":"Cytokine Growth Factor Rev"},{"issue":"3","key":"2022070621365120000_bib13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s11427-020-1643-8","article-title":"Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury","volume":"63","author":"Liu","year":"2020","journal-title":"Sci China Life Sci"},{"issue":"1","key":"2022070621365120000_bib14","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1080\/22221751.2020.1771219","article-title":"Viral loads in throat and anal swabs in children infected with SARS-CoV-2","volume":"9","author":"Yuan","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"2022070621365120000_bib15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13054-021-03555-z","article-title":"Implications of cardiac markers in risk-stratification and management for COVID-19 patients","volume":"25","author":"Li","year":"2021","journal-title":"Crit Care"},{"key":"2022070621365120000_bib16","first-page":"e00512","article-title":"Laboratory diagnosis of COVID-19: current issues and challenges","volume-title":"J Clin Microbiol","author":"Tang","year":"2020"},{"key":"2022070621365120000_bib17","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/CS20050086","article-title":"Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis","volume":"109","author":"Bustin","year":"2005","journal-title":"Clin Sci"},{"issue":"3","key":"2022070621365120000_bib18","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s40121-020-00324-3","article-title":"A narrative systematic review of the clinical utility of cycle threshold values in the context of COVID-19","volume":"9","author":"Rao","year":"2020","journal-title":"Infect Dis Ther"},{"issue":"9","key":"2022070621365120000_bib19","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1172\/JCI138554","article-title":"Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent","volume":"130","author":"Mazzoni","year":"2020","journal-title":"J Clin Invest"},{"issue":"1","key":"2022070621365120000_bib20","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"2022070621365120000_bib21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41392-021-00517-3","article-title":"Prognostic value of lymphocyte count in severe COVID-19 patients with corticosteroid treatment","volume":"6","author":"Lu","year":"2021","journal-title":"Signal Transduc Target Ther"},{"key":"2022070621365120000_bib22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40560-020-00453-4","article-title":"Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis","volume":"8","author":"Huang","year":"2020","journal-title":"J Intensive Care"},{"issue":"2","key":"2022070621365120000_bib23","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1016\/j.ijid.2012.06.006","article-title":"Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia","volume":"17","author":"Bordon","year":"2013","journal-title":"Int J Infect Dis"},{"key":"2022070621365120000_bib24","doi-asserted-by":"crossref","first-page":"8829674","DOI":"10.1155\/2020\/8829674","article-title":"COVID-19 and neutrophils: the relationship between hyperinflammation and neutrophil extracellular traps","volume":"2020","author":"Borges","year":"2020","journal-title":"Mediators Inflamm"},{"issue":"4","key":"2022070621365120000_bib25","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.4269\/ajtmh.20-1536","article-title":"Hematological abnormalities in COVID-19: a narrative review","volume":"104","author":"Rahman","year":"2021","journal-title":"Am J Trop Med Hyg"},{"key":"2022070621365120000_bib26","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijid.2021.03.066","article-title":"Circulating activated neutrophils in COVID-19: an independent predictor for mechanical ventilation and death","volume":"106","author":"Dennison","year":"2021","journal-title":"Int J Infect Dis"},{"issue":"4","key":"2022070621365120000_bib27","doi-asserted-by":"crossref","first-page":"e13698","DOI":"10.1111\/ijcp.13698","article-title":"Neutrophil\/lymphocyte ratio\u2014a marker of COVID-19 pneumonia severity","volume":"75","author":"Imran","year":"2021","journal-title":"Int J Clin Pract"},{"issue":"2","key":"2022070621365120000_bib28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/ijlh.13374","article-title":"Neutrophil-to-lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID-19","volume":"43","author":"Liu","year":"2021","journal-title":"Int J Lab Hematol"},{"key":"2022070621365120000_bib29"},{"key":"2022070621365120000_bib30"},{"key":"2022070621365120000_bib31","volume-title":"COVID-19 clinical management: living guidance","author":"World Health Organization","year":"2021"},{"issue":"4","key":"2022070621365120000_bib32","doi-asserted-by":"crossref","first-page":"100035","DOI":"10.1016\/j.cytox.2020.100035","article-title":"Tocilizumab for severe COVID-19 related illness \u2013 a community academic medical center experience","volume":"2","author":"Meleveedu","year":"2020","journal-title":"Cytokine X"},{"key":"2022070621365120000_bib33","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1186\/s12967-020-02571-x","article-title":"Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study","volume":"18","author":"Zhang","year":"2020","journal-title":"J Transl Med"},{"issue":"2","key":"2022070621365120000_bib34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3390\/v13020281","article-title":"Diagnostic SARS-CoV-2 cycle threshold value predicts disease severity, survival, and six-month sequelae in COVID-19 symptomatic patients","volume":"13","author":"Trunfio","year":"2021","journal-title":"Viruses"},{"issue":"1","key":"2022070621365120000_bib35","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ijmmb.2020.10.021","article-title":"No correlation between Ct values and severity of disease or mortality in patients with COVID 19 disease","volume":"39","author":"Shah","year":"2021","journal-title":"Indian J Med Microbiol"},{"key":"2022070621365120000_bib36","article-title":"Viral cultures for COVID-19 infectious potential assessment \u2013 a systematic review","author":"Jefferson","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"3","key":"2022070621365120000_bib37","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.resinv.2020.12.011","article-title":"The real-time reverse transcription-polymerase chain reaction threshold cycle values for severe acute respiratory syndrome coronavirus 2 predict the prognosis of coronavirus disease 2019 pneumonia","volume":"59","author":"Fukushima","year":"2021","journal-title":"Respir Investig"},{"issue":"11","key":"2022070621365120000_bib38","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/infdis\/jiaa150","article-title":"Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia","volume":"221","author":"Wang","year":"2020","journal-title":"J Infect Dis"},{"issue":"7","key":"2022070621365120000_bib39","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1515\/cclm-2020-0369","article-title":"Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis","volume":"58","author":"Henry","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"2022070621365120000_bib40","doi-asserted-by":"crossref","first-page":"106504","DOI":"10.1016\/j.intimp.2020.106504","article-title":"The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients","volume":"84","author":"Yang","year":"2020","journal-title":"Int Immunopharmacol"},{"issue":"5","key":"2022070621365120000_bib41","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00259-020-04735-9","article-title":"Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2","volume":"47","author":"Xu","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"10","key":"2022070621365120000_bib42","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1001\/jamainternmed.2020.3539","article-title":"Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy","volume":"180","author":"Grasselli","year":"2020","journal-title":"JAMA Intern Med"},{"issue":"8","key":"2022070621365120000_bib43","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S2213-2600(20)30225-3","article-title":"Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy","volume":"8","author":"George","year":"2020","journal-title":"Lancet Respir Med"},{"issue":"3","key":"2022070621365120000_bib44","first-page":"333","article-title":"An increased neutrophil\/lymphocyte ratio is an early warning signal of severe COVID-19]","volume":"40","author":"Xia","year":"2020","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"issue":"1","key":"2022070621365120000_bib45","first-page":"21","article-title":"Lymphocyte-to-C-reactive protein ratio may serve as an effective biomarker to determine COVID-19 disease severity","volume":"46","author":"Bal","year":"2020","journal-title":"Turk J Biochem"},{"issue":"4","key":"2022070621365120000_bib46","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1089\/jwh.2020.8472","article-title":"Sex and gender disparities in the COVID-19 pandemic","volume":"29","author":"Gausman","year":"2020","journal-title":"J Womens Health"},{"key":"2022070621365120000_bib47","volume-title":"Covid vaccines reduce the likelihood of hospitalisation by 80% after one dose in over 70s, data shows","author":"Good Morning Britain"},{"issue":"2","key":"2022070621365120000_bib48","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4038\/jccp.v51i2.7906","article-title":"COVID-19 vaccine landscape","volume":"51","author":"Seneviratne","year":"2020","journal-title":"J Ceylon Coll Physicians"}],"container-title":["Transactions of The Royal Society of Tropical Medicine and Hygiene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/116\/7\/628\/44489663\/trab182.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/116\/7\/628\/44489663\/trab182.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T21:37:40Z","timestamp":1657143460000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/trstmh\/article\/116\/7\/628\/6459965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,11]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,12,11]]},"published-print":{"date-parts":[[2022,7,6]]}},"URL":"https:\/\/doi.org\/10.1093\/trstmh\/trab182","relation":{},"ISSN":["0035-9203","1878-3503"],"issn-type":[{"value":"0035-9203","type":"print"},{"value":"1878-3503","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7]]},"published":{"date-parts":[[2021,12,11]]}}}