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Cited by 209Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 Research

The DOI matches its Crossref record; 68 of the 71 references it cites were found in a registry or an index.

Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis

Open access
Notarte, Kin Israel, de Oliveira, Maria Helena Santos, Peligro, Princess Juneire, Velasco, Jacqueline Veronica, Macaranas, Imee, Ver, Abbygail Therese, Pangilinan, Flos Carmeli, Pastrana, Adriel, Goldrich, Nathaniel, Kavteladze, David, Gellaco, Ma. Margarita Leticia, Liu, Jin, Lippi, Giuseppe, Henry, Brandon Michael, Fernández-de-las-Peñas, César·2022·Journal of Clinical Medicine
DOI 10.3390/jcm11247314PMC PMC9787827
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Abstract

Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.

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Figure 1 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram.
Figure 1 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram.CC BY · PubMed Central
Figure 2 Pooled analysis of odds ratio (OR) for the association between age older than 60 years and the presence of long COVID-19 symptoms [32,42,44].
Figure 2 Pooled analysis of odds ratio (OR) for the association between age older than 60 years and the presence of long COVID-19 symptoms [32,42,44].CC BY · PubMed Central
Figure 3 Pooled weighted mean difference (WMD) for the association between age as continuous variable and the presence of long COVID-19 symptoms [43,45,46].
Figure 3 Pooled weighted mean difference (WMD) for the association between age as continuous variable and the presence of long COVID-19 symptoms [43,45,46].CC BY · PubMed Central
Figure 4 Pooled analysis of odds ratio (OR) for the association between sex and the presence of long COVID-19 [32,42,43,44,45,46,50].
Figure 4 Pooled analysis of odds ratio (OR) for the association between sex and the presence of long COVID-19 [32,42,43,44,45,46,50].CC BY · PubMed Central
Figure 5 Plot of the risk of bias of those studies investigating age as a risk factor of long COVID-19 [10,26,27,28,29,30,31,32,33,35,36,37,38,39,40,41,42,43].
Figure 5 Plot of the risk of bias of those studies investigating age as a risk factor of long COVID-19 [10,26,27,28,29,30,31,32,33,35,36,37,38,39,40,41,42,43].CC BY · PubMed Central
Figure 6 Plot of the risk of bias of those studies investigating sex as a risk factor of long COVID-19 [1,32,42,43,44,45,46,47,48,49,50,51,52,54,55,56].
Figure 6 Plot of the risk of bias of those studies investigating sex as a risk factor of long COVID-19 [1,32,42,43,44,45,46,47,48,49,50,51,52,54,55,56].CC BY · PubMed Central
Figure 7 Plot of the risk of bias of those studies investigating medical comorbidities as a risk factor of long COVID-19 [4,29,39,44,52,53,56,58,60,61,62,63].
Figure 7 Plot of the risk of bias of those studies investigating medical comorbidities as a risk factor of long COVID-19 [4,29,39,44,52,53,56,58,60,61,62,63].CC BY · PubMed Central

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Metadata

Authors
Notarte, K. I., de Oliveira, M. H. S., Peligro, P. J., Velasco, J. V., Macaranas, I., Ver, A. T., Pangilinan, F. C., Pastrana, A., Goldrich, N., Kavteladze, D., Gellaco, M. M. L., Liu, J., Lippi, G., Henry, B. M., & Fernández-de-las-Peñas, C.
Affiliations
  • Johns Hopkins University (US)
  • Universidade Estadual de Maringá (BR)
  • University of Santo Tomas (PH)
  • New York Medical College (US)
  • University of Verona (IT)
  • Cincinnati Children's Hospital Medical Center (US)
  • Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28933 Madrid, Spain
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2022-12-09
Volume
11
Issue
24
Pages
7314
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm11247314
PMC
PMC9787827
OpenAlex
W4311974713
Cited by
209
References
71
Citations by year
2026: 19 · 2025: 55 · 2024: 78 · 2023: 56 · 2022: 1
FWCI
6.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fondo Europeo De Desarrollo Regional—Recursos REACT-UE del Programa Operativo de Madrid 2014–2020
Topics
  • Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
long COVID, risk factors, age, sex differences, female sex as risk factor, comorbidities, obesity, diabetes mellitus, lung disease, organ transplantation, COVID-19 pandemic, prognostic factors, risk of bias

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