Comorbid Chronic Diseases are Strongly Correlated with Disease Severity among COVID-19 Patients: A Systematic Review and Meta-Analysis
Hong Liu1, Shiyan Chen2, Min Liu1, Hao Nie3, Hongyun Lu4,*
1Department of Nutrition, the Third Xiangya Hospital of Central South University, Changsha, China. 2Department of Endocrinology & Metabolism, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. 3Department of Geriatrics, the First Affiliated Hospital of Hunan Normal University, Changsha, China. 4Department of Endocrinology & Metabolism, Zhuhai Hospital Affiliated with Jinan University, Zhuhai People’s Hospital, Zhuhai, China.
Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. In order to explore the effects of comorbid chronic diseases on clinical outcomes of COVID-19, a search was conducted in PubMed, Ovid MEDLINE, EMBASE, CDC, and NIH databases to April 25, 2020. A total of 24 peer-reviewed articles, including 10948 COVID-19 cases were selected. We found diabetes was present in 10.0%, coronary artery disease/cardiovascular disease (CAD/CVD) was in 8.0%, and hypertension was in 20.0%, which were much higher than that of chronic pulmonary disease (3.0%). Specifically, preexisting chronic conditions are strongly correlated with disease severity [Odds ratio (OR) 3.50, 95% CI 1.78 to 6.90], and being admitted to intensive care unit (ICU) (OR 3.36, 95% CI 1.67 to 6.76); in addition, compared to COVID-19 patients with no preexisting chronic diseases, COVID-19 patients who present with either diabetes, hypertension, CAD/CVD, or chronic pulmonary disease have a higher risk of developing severe disease, with an OR of 2.61 (95% CI 1.93 to 3.52), 2.84 (95% CI 2.22 to 3.63), 4.18 (95% CI 2.87 to 6.09) and 3.83 (95% CI 2.15 to 6.80), respectively. Surprisingly, we found no correlation between chronic conditions and increased risk of mortality (OR 2.09, 95% CI 0.26 to16.67). Taken together, cardio-metabolic diseases, such as diabetes, hypertension and CAD/CVD were more common than chronic pulmonary disease in COVID-19 patients, however, each comorbid disease was correlated with increased disease severity. After active treatment, increased risk of mortality in patients with preexisting chronic diseases may reduce.
Liu Hong,Chen Shiyan,Liu Min, et al. Comorbid Chronic Diseases are Strongly Correlated with Disease Severity among COVID-19 Patients: A Systematic Review and Meta-Analysis[J]. Aging and disease,
2020, 11(3): 668-678.
Table 1 Characteristics of the included studies and meta-analysis of the clinical symptoms and comorbid chronic diseases in patients with COVID-19.
Figure 1. Systematic literature review process. The flow diagram describes the systematic review of the literature for the proportion of comorbid chronic diseases in patients with COVID-19.
Study[ref]a
n
Symptoms(%)
Comorbidities(%)
non-severe
severe
fever
cough
fatigue or myalgia
shortness of breath or dyspnea
diarrhea
diabetes
hypertension
CAD/CVD
chronic pulmonary disease
All
M
F
age
All
M
F
age
mild
severe
mild
severe
mild
severe
mild
severe
mild
severe
mild
severe
mild
severe
mild
severe
mild
severe
Guan et al.,2020 [3]
926
540
386
45.0
173
100
73
52.0
88.1
91.9
67.3
70.5
37.8
39.9
15.1
37.6
3.5
5.8
5.7
16.2
13.5
23.7
1.8
5.8
0.6
3.5
Huang et al.,2020[18]
28
19
9
49.0
13
11
2
49.0
96.0
100.0
71.0
85.0
39.0
54.0
37.0
92.0
4.0
0.0
25.0
8.0
14.0
15.0
11.0
23.0
0.0
8.0
Yang et al.,2020 [6]
20
14
6
51.9
32
21
11
64.6
100.0
97.0
75.0
78.0
10.0
12.5
60.0
66.0
b
b
10.0
22.0
b
b
10.0
9.0
10.0
6.0
Xu et.al.,2020 [19]
29
16
13
39
33
19
14
45
83
73
79
82
45
58
b
b
0
9
0.0
3.0
3.0
12.0
b
b
0
3.0
Zhang et al.,2020[15]
82
38
44
51.5
58
33
25
64.0
72.0
87.9
54.9
77.6
62.2
67.2
24.4
41.4
11.0
15.5
11.0
13.8
24.4
37.9
3.7
6.9
0.0
3.4
Wang et al.,2020 [5]
102
53
51
51.0
36
22
14
66.0
98.0
100.0
59.8
58.3
35.3
33.3
19.6
63.9
7.8
16.7
5.9
22.2
21.6
58.3
10.8
25.0
1.0
8.3
Li et al.,2020[12]
58
29
29
41.9
25
15
10
53.7
86.2
88.0
70.7
96.0
17.2
20.0
3.4
28.0
8.6
8.0
0.0
28.0
5.2
8.0
0.0
4.0
1.7
16.0
Shi et al.,2020 [23]
334
161
173
60
82
44
38
74
81.1
76.8
34.7
34.1
12
18.3
27.2
31.7
4.5
1.2
12
24.4
23.4
59.8
6
29.3
1.8
8.5
Bhatraju etal.,2020[24]
b
b
b
b
24
15
9
64.0
b
50.0
b
88.0
b
b
b
88.0
b
b
b
58.0
b
b
b
b
b
16.7
Feng et al.,2020 [25]
b
b
b
b
476
271
205
b
0
85.9
0
59.4
0
12.6
0
24.4
0
11.0
0
10.3
0
23.7
0
8.0
0
4.6
Du et al.,2020 [26]
158
87
71
56
21
10
11
70.2
98.7
100
83.5
66.7
36.7
61.9
44.9
85.7
19.6
38.1
17.1
28.6
28.5
61.9
10.8
57.1
5.1
0
Liu et al.,2020 [27]
67
32
35
37
11
7
4
66
b
b
44.8
46.4
b
b
b
b
b
b
4.5
18.2
9
18.2
b
b
1.5
9.1
Grasselli et al.,2020[28]
b
b
b
b
1591
1304
287
63
b
b
b
b
b
b
b
b
b
b
b
11.3
b
32
b
14
b
2.6
Simonnet et al.,2020[30]
b
b
b
b
124
90
34
60
b
b
b
b
b
b
b
b
b
b
b
22.6
b
48.4
b
b
b
b
Total/Overall
1840
989
817
43.8c (37.0-60.0)d
2699
1962
737
60.9c (45.0-74.0) d
Prevalencee
90.0
99.0
64.0
71.0
32.0
37.0
27.0
55.0
8.0
8.0
95% CI
86.0-95.0
98.0-100.0
52.0-75.0
60.0-81.0
21.0-44.0
24.0-50.0
17.0-36.0
39.0-71.0
4.0-11.0
4.0-13.0
Qf
I2 (%)
95.5
94.0
95.4
91.7
95.6
94.2
94.4
95.9
81.2
92.5
Table 2 Characteristics of the included studies grouped by severe and non-severe cases and meta-analysis of the clinical symptoms and comorbid chronic diseases in patients with COVID-19.
Figure 2. The proportions of comorbid chronic diseases in patients with COVID-19. Forest plot showing the proportion of comorbid diabetes (A), coronary artery disease/cardiovascular disease (CAD/CVD) (B), hypertension (C), and chronic pulmonary disease (D) in SARS-CoV-2-infected patients. Weights were calculated from random-effects model analyses. The size of the squares reflects the relative weight of each study in the meta-analysis. Inserts within each panel show the total number of subjects analyzed (n) and prevalence (%) of the comorbid diseases (%), together with heterogeneity analysis carried out using the Q test and the among-studies variation (I2 index).
Figure 3. Correlation between comorbid chronic diseases and severe COVID-19 in SARS-CoV-2 infected patients. Forest plot showing the effects of comorbid diabetes (A), hypertension (B), CAD/CVD (C), and chronic pulmonary disease (D) on the risk of severe COVID-19 in SARS-CoV-2-infected patients. In this figures, the horizontal lines indicate the lower and upper limits of the 95% CI, and the size of the squares reflects the relative weight of each study in the meta-analysis. Weights were calculated from fixed-effects model analyses. Heterogeneity analysis was carried out using Q test and among-studies variation (I2 index).
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2020,
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