Journal Pre-proof

Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19)

infection: a systematic review and meta-analysis

Jing Yang, Ya Zheng, Xi Gou, Ke Pu, Zhaofeng Chen, Qinghong

Guo, Rui Ji, Haojia Wang, Yuping Wang, Yongning Zhou

PII: S1201-9712(20)30136-3
DOI: https://doi.org/10.1016/j.ijid.2020.03.017
Reference: IJID 4023

To appear in: International Journal of Infectious Diseases

Received Date: 28 February 2020

Revised Date: 4 March 2020
Accepted Date: 5 March 2020

Please cite this article as: Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Ji R, Wang H,
Wang Y, Zhou Y, Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19)
infection: a systematic review and meta-analysis, International Journal of Infectious Diseases
(2020), doi: https://doi.org/10.1016/j.ijid.2020.03.017

This is a PDF file of an article that has undergone enhancements after acceptance, such as
the addition of a cover page and metadata, and formatting for readability, but it is not yet the
definitive version of record. This version will undergo additional copyediting, typesetting and
review before it is published in its final form, but we are providing this version to give early
visibility of the article. Please note that, during the production process, errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal
pertain.

© 2019 Published by Elsevier.

Prevalence of comorbidities in the Novel Wuhan Coronavirus (COVID-19)
infection: a systematic review and meta-analysis.

Jing Yang1,2,#, Ya Zheng1,3,#, Xi Gou1,4,#, Ke Pu1,3, Zhaofeng Chen1,4, Qinghong

Guo1,3,4, Rui Ji1,3,4, Haojia Wang1, Yuping Wang1,3,*, Yongning Zhou1,3,4,*

1 Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou,

China
2 The First Clinical Medical School of Lanzhou University, Lanzhou, China

of
3 Key Laboratory for Gastrointestinal Diseases, Gansu Province, the First Hospital of
Lanzhou University, Lanzhou, China

ro
4 Gastrointestinal Endoscopy Center, Department of Gastroenterology, the First
Hospital of Lanzhou University, Lanzhou, China
-p
# These authors contributed equally to the work.
re
* Corresponding author:
lP

Yongning Zhou, Department of Gastroenterology, Gastrointestinal Endoscopy Center,

Key Laboratory for Gastrointestinal Diseases, Gansu Province, the First Hospital of
na

Lanzhou University, Lanzhou, Gansu Province, 730000, China. Tel:

+86-931-8356224. E-mail: [email protected];
Yuping Wang, Department of Gastroenterology, Key Laboratory for Gastrointestinal
ur

Diseases, Gansu Province, the First Hospital of Lanzhou University, Lanzhou, Gansu
Province, 730000, China. Tel: +86-931-8356323. E-mail: [email protected].
Jo

Highlights
 COVID -19 cases now confirmed in multiple countries.

 assessed the prevalence of comorbidities in infected patients.

 comorbidities are risk factors for severe patients compare with Non-severe.

1
 help the health sector guide vulnerable populations and assess the risk of

deterioration.

Background: An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the

epidemic is more widespread than initially estimated, with cases now confirmed in
multiple countries.
Aims: The aim of the meta-analysis was to assess the prevalence of comorbidities in
the COVID-19 infection patients and the risk of underlying diseases in severe patients
compared to non-severe patients.

of
Methods: A literature search was conducted using the databases PubMed, EMBASE,
and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence

ro
intervals (CIs) were pooled using random-effects models.

-p
Results: Eight studies were included in the meta- analysis, including 46248 infected
patients. The result showed the most prevalent clinical symptom was fever ( 91±3, 95%
re
CI 86-97% ), followed by cough (67±7, 95% CI 59-76%), fatigue ( 51±0, 95% CI
34-68% ) and dyspnea ( 30±4, 95% CI 21-40%). The most prevalent comorbidity
lP

were hypertension (17±7, 95% CI 14-22%) and diabetes ( 8±6, 95% CI 6-11% ),
followed by cardiovascular diseases ( 5±4, 95% CI 4-7% ) and respiratory system
disease( 2±0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds
na

ratio of hypertension, respiratory system disease, cardiovascular disease in severe

patients were (OR 2.36, 95% CI: 1.46-3.83) ,(OR 2.46, 95% CI: 1.76-3.44) and (OR
ur

3.42, 95% CI: 1.88-6.22)respectively.

Conclusion: We assessed the prevalence of comorbidities in the COVID-19 infection
Jo

patients and found underlying disease, including hypertension, respiratory system

disease and cardiovascular, may be a risk factor for severe patients compared with
Non-severe patients.

Keywords: 2019-nCoV, COVID-19, comorbidities, clinical characteristics,

epidemiological, meta-analysis;

2
1. Introduction
On December 31, 2019, a cluster of cases of “pneumonia of unknown origin” in
people associated with the Huanan Seafood Wholesale Market has been reported in
Wuhan, China. Only a few days later, Chinese health authorities confirmed that this
cluster was associated with a Novel Coronavirus 1 and was named COVID-19 by
WHO. Confirmed by comparative homology analysis, COVID-19 is closely
associated with bat-derived severe acute respiratory syndrome (SARS)-like
coronavirus (bat-SL-covzc45 and bat-SL-covzxc21) (with 88% identity,) but is far

of
away from SARS-Cov (about 79%) and MERS-Cov (about 50%) 2. A total of 77 658
confirmed cases, including 9162 with severe illness, and 2663 death had been

ro
reported，as of February 25, 2020, by the National Health Commission of China.
Huang et al first reported the clinical features of 41 confirmed patients, indicated 13
-p
(32%) of them had underlying diseases 3, including cardiovascular disease, diabetes,
hypertension, and chronic obstructive pulmonary disease. Subsequently, Wang et al
re
reported findings from 138 cases of COVID-19 the results suggested that 64(46.4%)
of them had comorbidities. Importantly, the patients admitted to the intensive care unit
lP

(ICU) had a higher number of comorbidities(72.2%) than those not admitted to the
ICU（37.3%）. This suggests that complications may be a risk factor for adverse
outcomes 4. Assessing the prevalence of these chronic diseases is the basis for
na

mitigating complications in patients with COVID-19 infections. However, the effort

was hampered by the limited number of cases.
ur

To get a more convincing result, we will provide a systematic evaluation and detail
not only estimate the Prevalence of comorbidities in all patients, also assess the risk of
Jo

underlying diseases in severe patients compared to non-severe patients. The result

may aid the management while developing policies for prevention, and response to
COVID-19 and its critical outcomes.

2. Methods
2.1. Search strategy and selection criteria

3
A systematic search was conducted on studies published from January 1, 2019 to
February 25, 2020 in PubMed, EMBASE, and Web of Science databases. Records
were managed by EndNote X 9.0 software to exclude duplicates. According to the
indices of the various databases, we use the search term “2019 novel coronavirus and
COVID-19” AND “comorbidities, clinical characteristics, epidemiological” without
any language restriction. To identify missing studies, we had checked the reference
list for each selected paper. Eligible studies should describe the epidemiological,
clinical features of (COVID-19), and the prevalence of Chronic diseases in infected
patients. Studies that (a) duplicate publications, (b) reviews, editorials, case reports,

of
letters, and family-based studies, (c) only children cases, were excluded. The steps of
the literature search are shown in Figure 1.

ro
2.2. Data extraction and analysis
The two investigators (J Yang and YP Wang) who performed the literature search also
-p
independently extracted the data from included studies. Disagreements were resolved
with a third investigator (YN Zhou) or by consensus. We extracted the following
re
variables: author, date, age, gender, number of participates in severe and Non-severe,
the prevalence of clinical symptoms such as fever, cough, fatigue, and dyspnea,
lP

together with comorbidities including hypertension, diabetes, respiratory system

disease, and cardiovascular diseases. All calculations were performed by STATA MP
na

version 13.0. The odds ratio (OR, 95% confidence intervals (CI)) was used to describe
the ratio of the probability of the Coronavirus occurring in severe patients vs.
Non-severe. Owing to heterogeneity within and between studies, a random effect
ur

model was used to estimating the average effect and its precision, which would give a
more conservative estimate of the 95% CI. Using the I 2 statistic and Cochran's Q test
Jo

to assess statistical heterogeneity.

3. Result
Terms initially searched a total of 108 articles. After we removed duplicates, checked
the title and abstract, and reviewed full-text, eight studies 3-10 eventually met the
predetermined inclusion and exclusion criteria. As of February 25, 2020, a total of

4
46248 participants were included in our meta‐ analysis. As presented in Table 1, the
median age was 46.0 years and 23871 (51.6%) were men.
The result of this meta-analysis showed the most prevalent clinical symptom was
fever ( 91±3, 95% CI 86-97% ), followed by cough (67±7, 95% CI 59-76%), fatigue
( 51±0, 95% CI 34-68% ) and dyspnea ( 30±4, 95% CI 21-40% ). However, the I 2
varying from 84.9% to 96.4% in the evaluates of the clinical features showed
significant statistic heterogeneity (p=0.00). The prevalence of comorbidities including
hypertension, diabetes, respiratory system disease, and cardiovascular diseases. As
shown in Figure 2 (inserts A, B, C, D), the most prevalent comorbidity were

of
hypertension ( 17±7, 95% CI 14-22% ) and diabetes ( 8±6, 95% CI 6-11% ),followed
by cardiovascular diseases ( 5±4, 95% CI 4-7% ) and respiratory system disease( 2±0,

ro
95% CI 1-3% ). In analysis by the proportion of comorbidities, the significant
heterogeneity observed for estimates of hypertension, diabetes and cardiovascular
-p
diseases (p=0.000), but not respiratory system disease (p=0.126) with an I 2 index
ranging from 39.9 to 87.5%.
re
In Figure 3, we analyzed the relationship between complications and severe group and
Non-severe group. A higher risk of with hypertension, respiratory system disease, and
lP

cardiovascular diseases in the severe group compared to those in Non-severe, the

result were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR
na

3.42, 95% CI: 1.88-6.22)respectively. They showed low heterogeneity, with I 2 from 0
to 39.3 %. However, it was not a statistically significant difference in diabetes, (OR
2.07, 95% CI: 0.89‐ 4.82).
ur

4. Discussion
Jo

The meta-analysis was based on data from 8 studies with laboratory- confirmed
COVID -19. All the cases were from hospitals in China. The result we observed more
men than women, statistics about 23871:22377 in the COVID-19 infection. MERS-
CoV and SARS- CoV have also been found to infect more males than females 11,12. It
is customary to think women are less likely to affect many bacteria and viruses than
men, partly because of their more robust innate and adaptive immune responses 13.

5
However, it may be related to the occupational risk factors for men in Huanan wet
market exposure history in Huang’s report 3. Aged people and severe patients are
more susceptible to COVID-19, this may be associated with a higher frequency of
comorbidities 9.
A meta-analysis of the comorbidities suggests that hypertension prevalent in
approximately 17% of the patients, diabetes, cardiovascular diseases, and respiratory
system disease were present in 8%, 5%, and 2% of the cases, respectively.
Hypertension, diabetes mellitus consistent with the prevalence of hypertension and
diabetes in China were 23.2%14 and 10.9%15 in adults. A recent study about influenza

of
illness suggested that compared to patients with no comorbidities, the risk of death for
severe patients more often in those who had chronic obstructive pulmonary disease

ro
(OR 1.49, 95% CI: 1.10-2.01), and in those who had cardiovascular disease(OR 2.92,
95% CI: 1.76-4.86 ), hypertension(OR 1.49,95% CI: 1.10-2.10)16. The comorbidities
-p
effect had also been noted to have similar effects in other respiratory illnesses, such as
MERS-CoV 11. In our study, the association also showed in hypertension,
re
cardiovascular diseases, and respiratory system disease group. Overall, the severe
patients were older 4 and had a more significant number of comorbid conditions than
lP

those Non-severe. These results suggest that age and comorbidities may be risk
factors for critical patients.
na

The diseases such as hypertension, diabetes, respiratory system disease,

cardiovascular diseases, and their susceptibility conditions, may be linked to the
pathogenesis of COVID-19. Chronic diseases share several standard features with
ur

infectious disorders, such as the proinflammatory state, and the attenuation of the
innate immune response. For instance, diabetes occurs in part because the
Jo

accumulation of activated innate immune cells in metabolic tissues leads to the release
of inflammatory mediators, especially, IL-1β and TNFα, which promotes systemic
insulin resistance and β-cell damage 17. Besides, metabolic disorders may lead to low
immune function by impairing macrophage and lymphocyte function 18, which may
make individuals more susceptible to disease complications 11. Recently, Guo et al 19
retrospectively analyzed the clinical data of patients with viral pneumonia and found

6
that the absolute count levels of CD3+ T cell, CD3+ CD8+ T cell and CD3+ CD4+ T
cell in the death group were significantly lower than those in the survival group,
suggesting that the levels of various inflammatory factors in the death group were
higher than those in the survival group. A prospective case control study about
seasonal influenza was conducted by Hong et al 20, Their result showed that diabetes
and chronic cardiovascular disease were significantly related to development of
complications, and diabetes was an independent risk factor for severe seasonal
influenza (odds ration OR: 3.63, 95% CI(1.15-11.51)，P=0.02). Furthermore, a study
analyzed the risk factors for Middle East Respiratory Syndrome Coronavirus

of
(MERS-CoV) patients, finding diabetes, Smoking, and heart disease were also
significantly associated with MERS-CoV illness 21.

ro
Limitations of this meta-analysis should be addressed. First, the high statistic
heterogeneity could be found. This may relate to the study designs and large variation
-p
among studies in the sample size (9 to 46248 patients). Second, different lengths of
follow-up may miss the event leading to heterogeneity. Owing to some patients are
re
still in hospital in the included studies. Third, because only a few studies compared
the comorbidities of severe and Non-severe patients, we did not conduct sensitivity
lP

analysis and subgroup analysis.

If causality exists between chronic diseases and COVID-19, it will help the health
na

sector guide vulnerable populations and assess the risk of deterioration. Lau et al 22
followed up the vaccinations of 91,605 people with diabetes, the results showed that
the flu vaccine could make the incidence of influenza and pneumonia in people with
ur

diabetes aged (<65 years) decreased by 43%, and diabetes in the elderly (≥65 years)
people fell 55%. The symptoms of COVID-19 are similar with those of influenza (e. g,
Jo

fever, cough or fatigue), and outbreaks occur during the year of a high prevalence of
respiratory diseases caused by influenza, respiratory syncytial virus, and other
respiratory viruses. Vaccines can still be useful in helping prevent flu and will reduce
possible confusion with the COVID-19 infection 23.
Hypertension, diabetes, respiratory system disease, and cardiovascular disease period
were identified as potentially important risk factors that should be included in future

7
vaccination recommendations. Given the limited level of evidence, more adequately
and powered study should be conducted to prove the association. The prevalence of
chronic diseases is increasing year by year, targeted public health vaccination
interventions must be adopted to better protect people with chronic diseases from
COVID-19 and other respiratory infections.

Funding Source
This project is supported by the Gansu Provincial COVID-19 Science and Technology
Major Project, China; Talent Innovation and Entrepreneurship Project of Lanzhou,

of
China (2019-RC-33); Excellence Program of the First Clinical Medical College of
Lanzhou University, China.

ro
Ethics
-p
The study does not require ethical approval because the meta-analysis are based on
published research and the original data are anonymous.
re
Conflict of interest
lP

The authors declared that they have no conflicts of interest to this work.
na

Conflict of Interest Statement

We declare that there are no potential conflicts of interest.

ur

Declaration of interests
Jo

☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.

8
References
1. Hui DS, E IA, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV
epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus
outbreak in Wuhan, China. Int J Infect Dis 2020; 91: 264-6.
2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and
epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.
Lancet 2020; 395: 565-74.
3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506.
4. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138
Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
Jama 2020.

of
5. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of
Coronavirus Disease 2019 in China. N Engl J Med 2020.

ro
6. Kui L, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel
coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J 2020.
7. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical

China Life Sciences 2020; 63: 364-74.

-p
indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science

8. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The

re
epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases
(COVID-19)-China, 2020. China CDC Weekly 2020; 2: 113-22.
9. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of
lP

140 patients infected by SARS-CoV-2 in Wuhan, China. Allergy 2020; 00: 1-12.
10. Zhang MQ, Wang XH, Chen YL, Zhao KL, Cai YQ, An CL, et al. Clinical features of
2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing. Zhonghua
jie he he hu xi za zhi 2020; 43: E013.
na

11. Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory
syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int J Infect Dis
2016; 49: 129-33.
ur

12. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S.
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus
Infection. Journal of immunology 2017; 198: 4046-53.
Jo

13. Jaillon S, Berthenet K, Garlanda C. Sexual Dimorphism in Innate Immunity. Clinical

reviews in allergy immunology 2019; 56: 308-21.
14. Hu S, Gao R, Liu L, Zhu M, Wang W, Wang Y, et al. Summary of the 2018 report on
cardiovascular diseases in China. Chin Circ J 2019; 34: 209.
15. Liu M, Liu SW, Wang LJ, Bai YM, Zeng XY, Guo HB, et al. Burden of diabetes,
hyperglycaemia in China from to 2016: Findings from the 1990 to 2016, global burden of
disease study. Diabetes Metab 2019; 45: 286-93.
16. Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk
for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;

9
347: f5061.
17. Odegaard JI, Chawla A. Connecting type 1 and type 2 diabetes through innate immunity.
Cold Spring Harbor perspectives in medicine 2012; 2: a007724.
18. Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two
epidemics. The Lancet Infectious diseases 2009; 9: 737-46.
19. Guo L, Wei D, Zhang X, Wu Y, Li Q, Zhou M, et al. Clinical Features Predicting
Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score. Front Microbiol
2019; 10: 2752.
20. Hong KW, Cheong HJ, Choi WS, Lee J, Wie SH, Baek JH, et al. Clinical courses and
outcomes of hospitalized adult patients with seasonal influenza in Korea, 2011-2012:
Hospital-based Influenza Morbidity & Mortality (HIMM) surveillance. Journal of infection
and chemotherapy 2014; 20: 9-14.
21. Alraddadi BM, Watson JT, Almarashi A, Abedi GR, Turkistani A, Sadran M, et al. Risk
Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi

of
Arabia, 2014. Emerging infectious diseases 2016; 22: 49-55.
22. Lau D, Eurich DT, Majumdar SR, Katz A, Johnson JA. Effectiveness of influenza

ro
vaccination in working-age adults with diabetes: a population-based cohort study. Thorax
2013; 68: 658-63.
23. Patel A, Jernigan DB. Initial public health response and interim clinical guidance for the
-p
2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020.
American journal of transplantation 2020; 20: 889-95.
re
lP
na
ur
Jo

10
Figure Legend

of
ro
-p
re
lP
na

Figure 1 Flow diagram of the number of studies screened and included in the
meta-analysis.
ur
Jo

11
 of
ro
Figure 2 Meta-analysis of the proportion of comorbidities in COVID-19 cases. A, B,
C, D represent proportions of hypertension, diabetes, Respiratory system disease, and
Cardiovascular disease. -p
re
lP
na
ur
Jo

Figure 3 The risk of comorbidities in severe patients compared to Non-severe patients.

(A) hypertension, (B) diabetes, (C) Respiratory system disease, (D) Cardiovascular
disease.

12
Table 1 Main Characteristics of included studies in the meta-analysis.

Study Date Patients Ag Symptom Coronavirus

(month （No.） e s (%) (%)
, day) (ye
ar)
All Ma Fe Cou fati Dys Hypert Diab Respirato Cardiova
le ver gh gue pnea ension etes ry system scular
disease diseases
Huang 12.16- 41 30 49. 98. 76. 44. 55.0 15.0 20.0 2.0 15.0
et al 01.02 0 0 0 0
Kui et 12.30- 137 61 57. 81. 48. 32. 19.0 9.5 10.2 1.5 7.3
al 01.24 0 8 2 1

of
01.10- 12 8 53. 83. 91. 25.0 16.7 8.3 33.3
Liu et al
01.21 7 3 7
Wang 01.01- 138 75 56. 98. 59. 69. 31.2 31.2 10.1 2.9 14.5

ro
et al 01.28 0 6 4 6
Zhang 01.06- 140 71 57. 91. 75. 75 36.7 30.0 12.1 1.4 5.0
et al 02.03 0 7 0 -p
Zhang 01.18- 9 5 35. 88. 55. 44. 0 11.1 0 0
et al 02.03 2 9 6 4
re
Guan - 109 64 47. 87. 67. 38. 18.6 14.9 7.4 1.4 2.5
et al 01.29 9 0 0 9 7 1
12.31- 446 22 45. 12.8 5.3 2.4 4.2
China
lP

02.11 72 98 9
CDC c
1
12.16- 462 23 46.
Total 02.03 48 87 0a
na

1
Prevale 91 67± 51± 30±4 17±7 8±6 2±0 5±4
nce ±3 7 0
±SE b
ur

86 59- 34- 21-4 14.0-22 6.0-1 1.0-3.0 4.0-7.0

95% CI -9 76 68 0 .0 1.0
Jo

7
92. 84. 96. 91.1 87.5 73.9 39.9 82.9
I 2 (%)
1 9 4
P for 0 0 0
0 0 0 0.126 0
heterog
eneity
a, average age; b, Meta-analysis for the prevalence was calculated from binary
random-effects model analysis; c, The Novel Coronavirus Pneumonia Emergency
Response Epidemiology Team

13