Prognostic models in COVID-19 infection that predict severity: a systematic review

Chepkoech Buttia^#^{1

2

3}, Erand Llanaj^{4

5

6

7}, Hamidreza Raeisi-Dehkordi^#^{8

9}, Lum Kastrati^#^{8

10

11}, Mojgan Amiri¹², Renald Meçani^{13

14}, Petek Eylul Taneri^{8

15}, Sergio Alejandro Gómez Ochoa⁸, Peter Francis Raguindin^{8

16

17}, Faina Wehrli⁸, Farnaz Khatami^{8

10

18}, Octavio Pano Espínola^{8

19

20}, Lyda Z Rojas²¹, Aurélie Pahud de Mortanges²², Eric Francis Macharia-Nimietz²³, Fadi Alijla^{8

10}, Beatrice Minder²⁴, Alexander B Leichtle²⁵, Nora Lüthi²⁶, Simone Ehrhard²⁶, Yok-Ai Que²⁷, Laurenz Kopp Fernandes^{28

29}, Wolf Hautz^#²⁶, Taulant Muka^#^{8

6}

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Jackiebuttia07@yahoo.com.
² Emergency Department, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 16C, 3010, Bern, Switzerland. Jackiebuttia07@yahoo.com.
³ Epistudia, Bern, Switzerland. Jackiebuttia07@yahoo.com.
⁴ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
⁵ ELKH-DE Public Health Research Group of the Hungarian Academy of Sciences, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁶ Epistudia, Bern, Switzerland.
⁷ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
⁸ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
¹⁰ Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
¹¹ Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
¹³ Department of Pediatrics, "Mother Teresa" University Hospital Center, Tirana, University of Medicine, Tirana, Albania.
¹⁴ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
¹⁵ HRB-Trials Methodology Research Network College of Medicine, Nursing and Health Sciences University of Galway, Galway, Ireland.
¹⁶ Swiss Paraplegic Research, Nottwil, Switzerland.
¹⁷ Faculty of Health Sciences, University of Lucerne, Lucerne, Switzerland.
¹⁸ Department of Community Medicine, Tehran University of Medical Sciences, Tehran, Iran.
¹⁹ Department of Preventive Medicine and Public Health, University of Navarre, Pamplona, Spain.
²⁰ Navarra Institute for Health Research, IdiSNA, Pamplona, Spain.
²¹ Research Group and Development of Nursing Knowledge (GIDCEN-FCV), Research Center, Cardiovascular Foundation of Colombia, Floridablanca, Santander, Colombia.
²² Faculty of Medicine, University of Bern, Bern, Switzerland.
²³ Thoracic Surgery Department, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁴ Public Health and Primary Care Library, University Library of Bern, University of Bern, Bern, Switzerland.
²⁵ University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, and Center for Artificial Intelligence in Medicine (CAIM), University of Bern, Bern, Switzerland.
²⁶ Emergency Department, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 16C, 3010, Bern, Switzerland.
²⁷ Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁸ Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
²⁹ Charité Universitätsmedizin Berlin, Berlin, Germany.

^# Contributed equally.

PMID: 36840867
PMCID: PMC9958330
DOI: 10.1007/s10654-023-00973-x

Prognostic models in COVID-19 infection that predict severity: a systematic review

Chepkoech Buttia et al. Eur J Epidemiol. 2023 Apr.

. 2023 Apr;38(4):355-372.

doi: 10.1007/s10654-023-00973-x. Epub 2023 Feb 25.

Authors

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Jackiebuttia07@yahoo.com.
² Emergency Department, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 16C, 3010, Bern, Switzerland. Jackiebuttia07@yahoo.com.
³ Epistudia, Bern, Switzerland. Jackiebuttia07@yahoo.com.
⁴ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
⁵ ELKH-DE Public Health Research Group of the Hungarian Academy of Sciences, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁶ Epistudia, Bern, Switzerland.
⁷ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
⁸ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
¹⁰ Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
¹¹ Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
¹³ Department of Pediatrics, "Mother Teresa" University Hospital Center, Tirana, University of Medicine, Tirana, Albania.
¹⁴ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
¹⁵ HRB-Trials Methodology Research Network College of Medicine, Nursing and Health Sciences University of Galway, Galway, Ireland.
¹⁶ Swiss Paraplegic Research, Nottwil, Switzerland.
¹⁷ Faculty of Health Sciences, University of Lucerne, Lucerne, Switzerland.
¹⁸ Department of Community Medicine, Tehran University of Medical Sciences, Tehran, Iran.
¹⁹ Department of Preventive Medicine and Public Health, University of Navarre, Pamplona, Spain.
²⁰ Navarra Institute for Health Research, IdiSNA, Pamplona, Spain.
²¹ Research Group and Development of Nursing Knowledge (GIDCEN-FCV), Research Center, Cardiovascular Foundation of Colombia, Floridablanca, Santander, Colombia.
²² Faculty of Medicine, University of Bern, Bern, Switzerland.
²³ Thoracic Surgery Department, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁴ Public Health and Primary Care Library, University Library of Bern, University of Bern, Bern, Switzerland.
²⁵ University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, and Center for Artificial Intelligence in Medicine (CAIM), University of Bern, Bern, Switzerland.
²⁶ Emergency Department, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 16C, 3010, Bern, Switzerland.
²⁷ Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁸ Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
²⁹ Charité Universitätsmedizin Berlin, Berlin, Germany.

^# Contributed equally.

PMID: 36840867
PMCID: PMC9958330
DOI: 10.1007/s10654-023-00973-x

Abstract

Current evidence on COVID-19 prognostic models is inconsistent and clinical applicability remains controversial. We performed a systematic review to summarize and critically appraise the available studies that have developed, assessed and/or validated prognostic models of COVID-19 predicting health outcomes. We searched six bibliographic databases to identify published articles that investigated univariable and multivariable prognostic models predicting adverse outcomes in adult COVID-19 patients, including intensive care unit (ICU) admission, intubation, high-flow nasal therapy (HFNT), extracorporeal membrane oxygenation (ECMO) and mortality. We identified and assessed 314 eligible articles from more than 40 countries, with 152 of these studies presenting mortality, 66 progression to severe or critical illness, 35 mortality and ICU admission combined, 17 ICU admission only, while the remaining 44 studies reported prediction models for mechanical ventilation (MV) or a combination of multiple outcomes. The sample size of included studies varied from 11 to 7,704,171 participants, with a mean age ranging from 18 to 93 years. There were 353 prognostic models investigated, with area under the curve (AUC) ranging from 0.44 to 0.99. A great proportion of studies (61.5%, 193 out of 314) performed internal or external validation or replication. In 312 (99.4%) studies, prognostic models were reported to be at high risk of bias due to uncertainties and challenges surrounding methodological rigor, sampling, handling of missing data, failure to deal with overfitting and heterogeneous definitions of COVID-19 and severity outcomes. While several clinical prognostic models for COVID-19 have been described in the literature, they are limited in generalizability and/or applicability due to deficiencies in addressing fundamental statistical and methodological concerns. Future large, multi-centric and well-designed prognostic prospective studies are needed to clarify remaining uncertainties.

Keywords: Biomarkers; COVID-19; ICU; Mortality; Prediction models; Systematic review.

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Conflict of interest statement

The authors have no disclosures to report.

Figures

**Fig. 1**
Flowchart of inclusions and exclusions adapted from PRISMA

**Fig. 2**
Visual summary of the findings on evaluated prognostic models

See this image and copyright information in PMC

References

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Prognostic models in COVID-19 infection that predict severity: a systematic review

Affiliations

Prognostic models in COVID-19 infection that predict severity: a systematic review

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical