Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in Istanbul, Turkey
MD Uluhan Sili, Pinar Ay, Ahmet Topuzoglu, Elif Huseyin Bilgin, Elif Tukenmez Tigen, Buket Erturk Sengel, Dilek Yagci Caglayik, Baran Balcan, Sehnaz Derya Kocakaya, Sehnaz Olgun Yildizeli, Fethi Gul, Beliz Bilgili, Rabia Can Sarinoglu, Aysegul Karahasan Yagci, Lutfiye Mulazimoglu Durmusoglu, Emel Eryuksel, Zekaver Odabasi, Haner Direskeneli, Sait Karakurt, Ismail Cinel, Volkan Korten
doi:10.1101/2020.10.09.20209775
Background Coronavirus disease 2019 quickly spread worldwide to become a pandemic. This study aimed to define the predictors of critical illness development within 28 days postadmission.
Methods We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. The development of critical illness, e.g., invasive mechanical ventilation and/or death, was followed for a period of 28 days postadmission. Demographic characteristics, number of comorbidities, illness severity at admission defined by the WHO scale, vital signs, laboratory findings and period of admission to the hospital were independent variables. Cox proportional hazards analysis was performed, and the C-index was calculated.
Results The median (IQR) age of the cohort was 55.0 (44.0-67.0) years, and 50.1% were male. The most common presenting symptoms were cough, dyspnea and fatigue. Overall, 65.2% of the patients had at least one comorbidity. Hydroxychloroquine was given to 99.2% of the patients. Critical illness developed in 45 (9.4%; 95% CI: 7.0%-12.4%) patients. In the multivariable analysis, age (HR: 1.05, p<0.001), number of comorbidities (HR: 1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR: 2.12, p=0.03) and LDH ≥350 U/L (HR: 2.04, p=0.03) were .
References
Allenbach, Saadoun, Maalouf, Multivariable prediction model of intensive care unit transfer and death: a French prospective cohort study of COVID-19 patients, medRxiv,
doi:10.1101/2020.05.04.20090118Anesi, Halpern, Delgado, Covid-19 related hospital admissions in the United States: needs and outcomes, BMJ,
doi:10.1136/bmj.m2082Barnes, Burnett, Allen, Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum, J Thromb Thrombolysis,
doi:10.1007/s11239-020-02138-zCen, Chen, Shen, Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019-a multi-centre observational study, Clin Microbiol Infect,
doi:10.1016/j.cmi.2020.05.041Galloway, Norton, Barker, A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: An observational cohort study, J Infect,
doi:10.1016/j.jinf.2020.05.064Gong, Ou, Qiu, A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China, Clin Infect Dis,
doi:10.1093/cid/ciaa443Korber, Fischer, Gnanakaran, Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2, bioRxiv,
doi:10.1101/2020.04.29.069054Lechien, Chiesa-Estomba, Place, Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019, J Intern Med,
doi:10.1111/joim.13089Liang, Liang, Ou, Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.2033Petrilli, Jones, Yang, Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study, BMJ,
doi:10.1136/bmj.m1966Potere, Valeriani, Candeloro, Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and metaanalysis, Crit Care,
doi:10.1186/s13054-020-03022-1Rivera-Izquierdo, Del, Valero-Ubierna, Rd, Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: A retrospective observational study, PLoS One,
doi:10.1371/journal.pone.0235107Rodriguez-Morales, Cardona-Ospina, Gutierrez-Ocampo, Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101623Singer, Deutschman, Seymour, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA,
doi:10.1001/jama.2016.0287Weissman, Crane-Droesch, Chivers, Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic, Ann Intern Med,
doi:10.7326/M20-1260Wiersinga, Rhodes, Cheng, Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review, JAMA,
doi:10.1001/jama.2020.12839Wu, Mcgoogan, Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention, JAMA,
doi:10.1001/jama.2020.2648Wynants, Van Calster, Collins, Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal, BMJ,
doi:10.1136/bmj.m1328Xu, Tian, Luo, Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study, Theranostics,
doi:10.7150/thno.46833Zheng, Peng, Xu, Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis, J Infect,
doi:10.1016/j.jinf.2020.04.021DOI record:
{
"DOI": "10.1101/2020.10.09.20209775",
"URL": "http://dx.doi.org/10.1101/2020.10.09.20209775",
"abstract": "<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. This study aimed to define the predictors of critical illness development within 28 days postadmission.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. The development of critical illness, e.g., invasive mechanical ventilation and/or death, was followed for a period of 28 days postadmission. Demographic characteristics, number of comorbidities, illness severity at admission defined by the WHO scale, vital signs, laboratory findings and period of admission to the hospital were independent variables. Cox proportional hazards analysis was performed, and the C-index was calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The median (IQR) age of the cohort was 55.0 (44.0-67.0) years, and 50.1% were male. The most common presenting symptoms were cough, dyspnea and fatigue. Overall, 65.2% of the patients had at least one comorbidity. Hydroxychloroquine was given to 99.2% of the patients. Critical illness developed in 45 (9.4%; 95% CI: 7.0%-12.4%) patients. In the multivariable analysis, age (HR: 1.05, p<0.001), number of comorbidities (HR: 1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR: 2.12, p=0.03) and LDH ≥350 U/L (HR: 2.04, p=0.03) were independently associated with critical illness development. The WHO scale on admission was the strongest predictor of critical illness (HR: 4.15, p<0.001). Prognosis improved within the study period (p<0.05). The C-index of the model was 0.92.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Age, comorbidity number, WHO scale, LDH and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seems to be decreasing as the pandemic advances.</jats:p></jats:sec><jats:sec><jats:title>summary</jats:title><jats:p>We analyzed 477 confirmed COVID-19 patients for the development of critical illness, e.g., invasive mechanical ventilation and/or death within 28 days postadmission. Age, comorbidity number, WHO scale, LDH and procalcitonin were independently associated with critical illness development.</jats:p></jats:sec>",
"accepted": {
"date-parts": [
[
2020,
10,
11
]
]
},
"author": [
{
"ORCID": "http://orcid.org/0000-0002-9939-9298",
"affiliation": [],
"authenticated-orcid": false,
"family": "Sili",
"given": "Uluhan",
"sequence": "first"
},
{
"ORCID": "http://orcid.org/0000-0002-3303-1343",
"affiliation": [],
"authenticated-orcid": false,
"family": "Ay",
"given": "Pinar",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-7497-548X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Topuzoglu",
"given": "Ahmet",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-5048-9970",
"affiliation": [],
"authenticated-orcid": false,
"family": "Bilgin",
"given": "Huseyin",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2027-4116",
"affiliation": [],
"authenticated-orcid": false,
"family": "Tigen",
"given": "Elif Tukenmez",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2182-4693",
"affiliation": [],
"authenticated-orcid": false,
"family": "Sengel",
"given": "Buket Erturk",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-3473-8073",
"affiliation": [],
"authenticated-orcid": false,
"family": "Caglayik",
"given": "Dilek Yagci",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-1804-1970",
"affiliation": [],
"authenticated-orcid": false,
"family": "Balcan",
"given": "Baran",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2910-6813",
"affiliation": [],
"authenticated-orcid": false,
"family": "Kocakaya",
"given": "Derya",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-3236-3995",
"affiliation": [],
"authenticated-orcid": false,
"family": "Yildizeli",
"given": "Sehnaz Olgun",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-6426-6436",
"affiliation": [],
"authenticated-orcid": false,
"family": "Gul",
"given": "Fethi",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-3466-0771",
"affiliation": [],
"authenticated-orcid": false,
"family": "Bilgili",
"given": "Beliz",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-9222-8659",
"affiliation": [],
"authenticated-orcid": false,
"family": "Sarinoglu",
"given": "Rabia Can",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1560-2624",
"affiliation": [],
"authenticated-orcid": false,
"family": "Yagci",
"given": "Aysegul Karahasan",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-6973-473X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Durmusoglu",
"given": "Lutfiye Mulazimoglu",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-2194-8066",
"affiliation": [],
"authenticated-orcid": false,
"family": "Eryuksel",
"given": "Emel",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-8091-6999",
"affiliation": [],
"authenticated-orcid": false,
"family": "Odabasi",
"given": "Zekaver",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-2598-5806",
"affiliation": [],
"authenticated-orcid": false,
"family": "Direskeneli",
"given": "Haner",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-6699-5798",
"affiliation": [],
"authenticated-orcid": false,
"family": "Karakurt",
"given": "Sait",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-7595-1295",
"affiliation": [],
"authenticated-orcid": false,
"family": "Cinel",
"given": "Ismail",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-9991-814X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Korten",
"given": "Volkan",
"sequence": "additional"
}
],
"container-title": [],
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2020,
10,
11
]
],
"date-time": "2020-10-11T18:20:11Z",
"timestamp": 1602440411000
},
"deposited": {
"date-parts": [
[
2024,
4,
23
]
],
"date-time": "2024-04-23T16:29:54Z",
"timestamp": 1713889794000
},
"group-title": "Infectious Diseases (except HIV/AIDS)",
"indexed": {
"date-parts": [
[
2024,
4,
23
]
],
"date-time": "2024-04-23T17:10:38Z",
"timestamp": 1713892238461
},
"institution": [
{
"name": "medRxiv"
}
],
"is-referenced-by-count": 3,
"issued": {
"date-parts": [
[
2020,
10,
11
]
]
},
"link": [
{
"URL": "https://syndication.highwire.org/content/doi/10.1101/2020.10.09.20209775",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "246",
"original-title": [],
"posted": {
"date-parts": [
[
2020,
10,
11
]
]
},
"prefix": "10.1101",
"published": {
"date-parts": [
[
2020,
10,
11
]
]
},
"publisher": "Cold Spring Harbor Laboratory",
"reference": [
{
"key": "2020102016450708000_2020.10.09.20209775v1.1",
"unstructured": "Republic of Turkey Ministry of Health. COVID-19 Weekly Situation Report 13/07/2020 – 19/07/2020, https://dosyamerkez.saglik.gov.tr/Eklenti/38021,covid-19-weekly-situation-report---29-weekpdf.pdf?0&_tag1=44DBE7E25D380A645A4780C04D8C19C0EF692249 (accessed 17 August 2020)."
},
{
"key": "2020102016450708000_2020.10.09.20209775v1.2",
"unstructured": "Republic of Turkey Ministry of Health. COVID-19 Rehberi (Guideline), https://covid19bilgi.saglik.gov.tr/tr/covid-19-rehberi.html (accessed 17 August 2020)."
},
{
"DOI": "10.1001/jama.2020.12839",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.3"
},
{
"DOI": "10.1001/jama.2020.2648",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.4"
},
{
"DOI": "10.1186/s13054-020-03022-1",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.5"
},
{
"DOI": "10.1136/bmj.m1328",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.6"
},
{
"DOI": "10.1136/bmj.m2082",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.7"
},
{
"DOI": "10.7326/M20-1260",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.8"
},
{
"key": "2020102016450708000_2020.10.09.20209775v1.9",
"unstructured": "World Health Organization. WHO R&D Blueprint-novel Coronavirus-COVID-19 Therapeutic Trial Synopsis, https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf (accessed 17 August 2020)."
},
{
"DOI": "10.1001/jama.2016.0287",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.10"
},
{
"DOI": "10.7150/thno.46833",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.11"
},
{
"DOI": "10.1056/NEJMc2010419",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.12"
},
{
"DOI": "10.1016/j.ejim.2020.06.002",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.13"
},
{
"DOI": "10.1371/journal.pone.0235107",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.14"
},
{
"DOI": "10.1111/joim.13089",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.15"
},
{
"DOI": "10.1016/j.tmaid.2020.101623",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.16"
},
{
"DOI": "10.1136/bmj.m1966",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.17"
},
{
"DOI": "10.1093/cid/ciaa674",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.18"
},
{
"DOI": "10.1016/j.jinf.2020.04.021",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.19"
},
{
"key": "2020102016450708000_2020.10.09.20209775v1.20",
"unstructured": "Turkiye Istatistik Kurumu (Turkish Institute of Statistics). Turkiye Saglik Arastirmasi (Health Report of Turkey), http://www.tuik.gov.tr/PreTablo.do?alt_id=1095 (accessed 17 August 2020)."
},
{
"DOI": "10.1016/j.jinf.2020.05.064",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.21"
},
{
"DOI": "10.1001/jamainternmed.2020.2033",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.22"
},
{
"DOI": "10.1016/j.cmi.2020.05.041",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.23"
},
{
"DOI": "10.1093/cid/ciaa443",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.24"
},
{
"DOI": "10.1101/2020.05.04.20090118",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.25"
},
{
"DOI": "10.1007/s11239-020-02138-z",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.26"
},
{
"DOI": "10.1101/2020.04.29.069054",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.27"
},
{
"DOI": "10.1101/2020.04.14.20060160",
"doi-asserted-by": "publisher",
"key": "2020102016450708000_2020.10.09.20209775v1.28"
}
],
"reference-count": 28,
"references-count": 28,
"relation": {
"is-preprint-of": [
{
"asserted-by": "subject",
"id": "10.36519/idcm.2023.206",
"id-type": "doi"
}
]
},
"resource": {
"primary": {
"URL": "http://medrxiv.org/lookup/doi/10.1101/2020.10.09.20209775"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"subtype": "preprint",
"title": "Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in Istanbul, Turkey",
"type": "posted-content"
}
