Abstract
Background:
In this study, we aimed to assess the prevalence of comorbidities in the confirmed COVID-19 patients. This might help showing which comorbidity might pose the patients at risk of more severe symptoms.
Methods:
We searched all relevant databases on April 7th, 2020 using the keywords (“novel coronavirus” OR COVID-19 OR SARS-CoV-2 OR Coronavirus) AND (comorbidities OR clinical characteristics OR epidemiologic*). We reviewed 33 papers’ full text out of 1053 papers. There were 32 papers from China and 1 from Taiwan. There was no language or study level limit. Prevalence of comorbidities including hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic kidney disease, malignancies, cerebrovascular diseases, chronic liver disease and smoking were extracted to measure the pooled estimates. We used OpenMeta and used random-effect model to do a single arm meta-analysis.
Results:
The mean age of the diagnosed patients was 51 years. The male to female ratio was 55 to 45. The most prevalent finding in the confirmed COVID-19 patients was hypertension, which was found in 1/5 of the patients (21%). Other most prevalent finding was diabetes mellitus (DM) in 11%, cerebrovascular disease in 2.4%, cardiovascular disease in 5.8%, chronic kidney disease in 3.6%, chronic liver disease in 2.9%, chronic pulmonary disease in 2.0%, malignancy in 2.7%, and smoking in 8.7% of the patients.
Conclusion:
COVID-19 infection seems to be affecting every race, sex, age, irrespective of health status. The risk of symptomatic and severe disease might be higher due to the higher age which is usually accompanied with comorbidities. However, comorbidities do not seem to be the prerequisite for symptomatic and severe COVID-19 infection, except hypertension.
Key Words: Comorbidities, Coronavirus, COVID-19, Systematic review
Introduction
We are still unaware of many facts about the new coronavirus that is called COVID-19. In the beginning of its spread in Wuhan, China, the transmission and infectivity rate was reported very low, leading everyone to believe that the mortality rate was even lower than a seasonal flu, and taking it even less seriously. The first reports were noting that it only affects older people with comorbidities and only they die because of inefficient immune system following multiple comorbidities. The threat was not considered seriously and later after it spread to other countries, doctors were seeing even younger patients that were dying despite having no past medical history, and the patient’s status was aggravating so fast in hours that no one could help save the lives. Further studies showed cytokine storm as a reason which is an exaggerated immune response to the infection regardless of having comorbidities. Thus, simply having chronic conditions does not determine the prognosis.
In this study, we aimed to assess the prevalence of comorbidities in the confirmed COVID-19 patients. This might help showing which comorbidity might pose the patients at risk of more severe symptoms.
Materials and Methods
Search strategy
In order to identify all relevant studies, databases including EMBASE, PubMed, and google scholar were searched and papers published in the past year were screened carefully until April 7th, 2020 using title and abstract. Records were imported to EndNote X9 citation manager and duplicates were excluded. The following search terms were employed to ensure inclusion of all relevant studies: (“novel coronavirus” OR COVID-19 OR SARS-CoV-2 OR Coronavirus) AND (comorbidities OR clinical characteristics OR epidemiologic*)
Inclusion and Exclusion Criteria
All articles with any design and study level (levels 1-4) that reported the prevalence of comorbidities among the confirmed COVID-19 patients were included. There was no language limit. We used the translated abstract of non-English articles. We excluded papers concerning children and papers without epidemiological information.
Data extraction and statistical analysis
All stages of the meta-analysis were done by the two authors (AK and AB) independently. Prevalence of comorbidities including hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic kidney disease, malignancies, cerebrovascular diseases, chronic liver disease and smoking were extracted to measure the pooled estimates [Table 1]. The latest version of the statistical software OpenMeta [Analyst] (1) was used to do a single arm Meta-analysis. This analysis took study effects into account, and the results were calculated by a binary random-effect method (Dersimonian-Laird). A confidence interval of 95% was selected and the I2 statistic and Cochran’s Q test were measured to assess statistical heterogeneity. Forest plots were used to illustrate the prevalence with 95% confidence interval.
Table 1.
Data extracted using 33 papers
| First Author | Publication Date | Country | Number of patients | Sex (M/F) | Age (mean or median) | Age (SD or range) | HTN | DM | Malignancy | Chronic Lung Disease | Cardio vascular Disease | Chronic Liver Disease | Cerebro Vascular Disease | Chronic Kidney Disease | Smoking | 
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Yingzhen Du, et al. | 4/4/2020 | China | 85 | 62/23 | 66 | 14 | 32 | 19 | 6 | 2 | 10 | 5 | 3 | ||
| Lang Wang, et al. | 4/3/2020 | China | 339 | 166/173 | 69 | 65-76 | 138 | 54 | 15 | 21 | 53 | 2 | 21 | 13 | |
| ChaominWu, et al. | 3/14/2020 | China | 201 | 128/73 | 51 | 43-60 | 32 | 22 | 1 | 5 | 8 | 7 | 2 | ||
| Xiao Tang, et al. | 4/1/2020 | China | 148 | 105/43 | 62 | 47-69 | 70 | 35 | 31 | 9 | 43 | ||||
| Qingxian Cai, et al. | 4/3/2020 | China | 298 | 149/149 | 47 | 33-61 | 38 | 19 | 4 | 11 | 8 | ||||
| Wei Liu, et al. | 3/3/2020 | China | 78 | 39/39 | 38 | 33-57 | 8 | 5 | 4 | 2 | 5 | ||||
| Xiao-Wei Xu, et al. | 2/23/2020 | China | 62 | 35/27 | 41 | 32-52 | 5 | 1 | 1 | 7 | 1 | 1 | |||
| Tao Chen, et al. | 3/29/2020 | China | 274 | 171/103 | 62 | 44-70 | 93 | 47 | 7 | 18 | 23 | 11 | 4 | 4 | 12 | 
| Jiangshan Lian, et al. | 3/27/2020 | China | 652 | 349/303 | 41 | 11.38 | 73 | 33 | 3 | 0 | 5 | 25 | 5 | 46 | |
| Jianlei Cao, et al. | 4/3/2020 | China | 102 | 53/49 | 54 | 37-67 | 28 | 11 | 4 | 10 | 5 | 2 | 6 | 4 | |
| Zhongliang Wang, et al. | 3/17/2020 | China | 69 | 32/37 | 42 | 35-62 | 9 | 7 | 4 | 4 | 8 | 1 | |||
| Hansheng Xie, et al. | 4/3/2020 | China | 79 | 44/35 | 60 | 48-66 | 14 | 8 | 7 | ||||||
| Yan Deng, et al. | 3/27/2020 | China | 109 death | 73/36 | 69 | 62-74 | 40 | 17 | 6 | 22 | 13 | ||||
| 116 recovered | 51/65 | 40 | 33-57 | 18 | 9 | 2 | 3 | 4 | |||||||
| Weina Guo, et al. | 4/2/2020 | China | 174 | 76/98 | 59 | 49-67 | 43 | 37 | 17 | 14 | 32 | 8 | |||
| Wei-jie Guan, et al. | 3/29/2020 | China | 1590 | 904/674 | 49 | 16 | 269 | 130 | 130 | 24 | 59 | 24 | 30 | 269 | |
| Xi Jin, et al. | 3/28/2020 | China | 74 GI symptoms | 37/37 | 46 | 14 | 12 | 7 | 0 | 0 | 1 | 8 | 0 | ||
| 577 no GI symptoms | 294/283 | 45 | 14 | 88 | 41 | 6 | 1 | 4 | 17 | 6 | |||||
| Wen-Hsin Hsih, et al. | 3/30/2020 | Taiwan | 43 | 17/26 | 34 | 3-68 | 2 | 4 | 2 | 4 | 1 | 1 | |||
| Nanshan Chen, et al. | 2/3/2020 | China | 99 | 67/32 | 56 | 13 | 1 | 3 | |||||||
| Rui Wang, et al. | 4/3/2020 | China | 5 | 3 to 2 | 58 | 47-67 | 4 | 1 | 5 | ||||||
| L. Zhang, et al. | 4/1/2020 | China | 28 | 17/11 | 65 | 56-70 | 4 | 1 | 2 | ||||||
| Xiaoli Zhang, et al. | 3/25/2020 | China | 72 normal imaging | 33/39 | 35 | 14 | 4 | 4 | 0 | 0 | 0 | 2 | 0 | ||
| 573 abnormal imaging | 295/278 | 47 | 14 | 96 | 44 | 6 | 1 | 5 | 23 | 6 | |||||
| Jin-Jin Zhang, et al. | 2/23/2020 | China | 140 | 71/69 | 57 | 25-87 | 42 | 17 | 2 | 7 | 3 | 2 | 9 | ||
| W. Guan, et al. | 2/29/2020 | China | 1099 | 640/459 | 47 | 35-58 | 165 | 81 | 10 | 12 | 27 | 15 | 8 | 137 | |
| Chaolin Huang, et al. | 1/28/2020 | China | 41 | 30/11 | 49 | 41-58 | 6 | 8 | 1 | 1 | 6 | 1 | 3 | ||
| Yingxia Liu, et al. | 2/13/2020 | China | 12 | 8 to 4 | 54 | 10-72 | 3 | 2 | 0 | 1 | 4 | 0 | 2 | ||
| DaweiWang, et al. | 2/8/2020 | China | 138 | 75/63 | 56 | 42-68 | 43 | 14 | 10 | 4 | 20 | 4 | 7 | 4 | |
| Jie Li, et al. | 1/1/2020 | China | 17 | 9 to 8 | 45 | 13 | 1 | 1 | 3 | ||||||
| Jian Wu, et al. | 2/29/2020 | China | 80 | 39/41 | 46 | 15.42 | 1 | 0 | 1 | ||||||
| Kui Liu, et al. | 2/12/2020 | China | 137 | 61/76 | 57 | 20-83 | 13 | 14 | 2 | 2 | 10 | ||||
| Wenhua Liang, et al. | 2/19/2020 | China | 1590 | 18 | 111 | ||||||||||
| Yichun Cheng, et al. | 4/6/2020 | China | 701 | 367/334 | 63 | 50-71 | 233 | 100 | 32 | 13 | 14 | ||||
| Xiaobing Wang, et al. | 4/7/2020 | China | 1012 | 524/488 | 50 | 39-58 | 46 | 27 | 20 | 15 | |||||
| Ya-nan Han, et al. | 4/7/2020 | China | 25 | 12 to 13 | 44 | 22-70 | 7 | 9 | |||||||
Results
Study characteristics
We included 33 studies for data extraction out of 1053 papers found on COVID-19 on April 7th, 2020 [Figure 1]. There were 32 papers from China and 1 paper from Taiwan (2). All 33 papers were in English language. In total, these studies included 9,249 patients comprising of 5,036 men and 4,191 women with confirmed COVID-19 since December 2019. (2-34)
Figure 1.
PRISMA flow diagram. (From Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group [2009]. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 6[7]:e1000097. https://doi.org/10.1371/journal.pmed.1000097.)
Test of heterogeneity
We performed statistical testing for heterogeneity to determine if the prevalence of comorbidities was the same in all studies. Cochran Q result rejected the null hypothesis that there is no heterogeneity between studies if P value was <0.05. Moreover, I2 revealed that how much percent of the variation across the studies was because of heterogeneity rather than sampling error and chance. Following rule of thumb, we considered I2 greater than 40% as substantial heterogeneity. Considering the presence of heterogeneity in all fields, we used random-effects model to conduct the meta-analysis.
Age distribution
Based on the random effect model after inclusion of 33 studies, the mean age of the confirmed COVID-19 patients was 51 years (95% CI, 49-54 years old). Cochran Q statistics showed 95% heterogeneity among studies which was high and significant (Q=655, P<0.001, I2=95) [Figure 2].
Figure 2.
Forest plot of the age distribution using random effect model
Sex distribution
Based on the random effect model after inclusion of 32 studies, 55% (95% CI, 53%-57%) of the patients were men while 45% (95% CI, 43%-47%) were women. Cochran Q statistics showed 74% heterogeneity among studies which was high and significant (Q=120, P<0.001, I2=74) [Figures 3; 4].
Figure 3.
Forest plot of the Sex (male) ratio using random effect model
Figure 4.
Forest plot of the Sex (Female) ratio using random effect model
Prevalence of cerebrovascular disease
Based on the random effect model after inclusion of 8 studies, the prevalence of cerebrovascular disease among the confirmed COVID-19 patients was 2.4% (95% CI, 1.5%-3.4%). Cochran Q statistics showed 64% heterogeneity among studies which was high and significant (Q=19, P=0.007, I2=64) [Figure 5].
Figure 5.
Forest plot of the cerebrovascular disease prevalence among COVID-19 patients using random effect model
Prevalence of cardiovascular disease
Based on the random effect model after inclusion of 23 studies, the prevalence of cardiovascular disease among the confirmed COVID-19 patients was 5.8% (95% CI, 4.5%-7.1%). Cochran Q statistics showed 91% heterogeneity among studies which was high and significant (Q=250, P<0.001, I2=91) [Figure 6].
Figure 6.
Forest plot of the cardiovascular disease prevalence among COVID-19 patients using random effect model
Prevalence of chronic kidney disease
Based on the random effect model after inclusion of 17 studies, the prevalence of chronic kidney disease among the confirmed COVID-19 patients was 3.6% (95% CI, 2.0%-5.1%). Cochran Q statistics showed 96% heterogeneity among studies which was high and significant (Q=368, P<0.001, I2=96) [Figure 7].
Figure 7.
Forest plot of the chronic kidney disease prevalence among COVID-19 patients using random effect model
Prevalence of diabetes mellitus
Based on the random effect model after inclusion of 29 studies, the prevalence of diabetes mellitus among the confirmed COVID-19 patients was 11% (95% CI, 8.9%-12.7%). Cochran Q statistics showed 89% heterogeneity among studies which was high and significant (Q=252, P<0.001, I2=89) [Figure 8].
Figure 8.
Forest plot of the diabetes melittus prevalence among COVID-19 patients using random effect model
Prevalence of hypertension
Based on the random effect model after inclusion of 29 studies, the prevalence of hypertension among the confirmed COVID-19 patients was 21% (95% CI, 17%-24.6%). Cochran Q statistics showed 96% heterogeneity among studies which was high and significant (Q=687, P<0.001, I2=96) [Figure 9].
Figure 9.
Forest plot of the hypertension prevalence among COVID-19 patients using random effect model
Prevalence of liver disease
Based on the random effect model after inclusion of 20 studies, the prevalence of liver disease among the confirmed COVID-19 patients was 2.9% (95% CI, 2.0%-3.7%). Cochran Q statistics showed 62% heterogeneity among studies which was high and significant (Q=50, P<0.001, I2=62) [Figure 10].
Figure 10.
Forest plot of the chronic liver disease prevalence among COVID-19 patients using random effect model
Prevalence of pulmonary disease
Based on the random effect model after inclusion of 25 studies, the prevalence of chronic pulmonary disease among the confirmed COVID-19 patients was 2.0% (95% CI, 1.4%-2.5%). Cochran Q statistics showed 85% heterogeneity among studies which was high and significant (Q=162, P<0.001, I2=85) [Figure 11].
Figure 11.
Forest plot of the chronic pulmonary disease prevalence among COVID-19 patients using random effect model
Prevalence of malignancy
Based on the random effect model after inclusion of 24 studies, the prevalence of malignancy among the confirmed COVID-19 patients was 2.7% (95% CI, 1.9%-3.5%). Cochran Q statistics showed 87% heterogeneity among studies which was high and significant (Q=181, P<0.001, I2=87) [Figure 12].
Figure 12.
Forest plot of the malignancy prevalence among COVID-19 patients using random effect model
Prevalence of smoking
Based on the random effect model after inclusion of 10 studies, the prevalence of smoking among the confirmed COVID-19 patients was 8.6% (95% CI, 5.8%-11.4%). Cochran Q statistics showed 88% heterogeneity among studies which was high and significant (Q=74, P<0.001, I2=88) [Figure 13].
Figure 13.
Forest plot of the smoking prevalence among COVID-19 patients using random effect model
Discussion
In this study, we aimed to assess the prevalence of accompanying comorbidities in patients tested positive for COVID-19. It seems that the most prevalent comorbidity was hypertension while other comorbidities are counting for less than 10% among the patients.
One main limitation of our study was that most of the studies were from the Chinese population which differences in race and ethnicity may play a role particularly when we see differences in mortality rates around the world. We assume that the prevalence and rates might differ in future papers that consider other populations. Another limitation of our study is that we are not sure if the prevalence reporting were complete because most of these papers emerged at the time that papers were published too fast with no peer review. We are only trusting the current literature so far from China and we have to be vigilant about the accuracy of data. Thus, we did not perform quality assessment because we were to include all published papers.
The mean age of the diagnosed patients was 51 years. It is intuitive that younger age groups are not showing too severe symptoms to make them refer to the hospitals and thus they remain undiagnosed. The male to female ratio was 55/45 showing slightly higher infection rate or probably slightly more severe presentation to refer the patients to the hospitals. This might be due to the fact that men are spending more time out of house at work, which causes men contracting the disease first and slightly more severe.
The most prevalent finding in the confirmed COVID-19 patients was hypertension, which was found in 1/5 of the patients and is consistent with the tendency of the virus binding with ACE2 receptor. Other most prevalent finding was diabetes mellitus (DM) in almost 10% of the patients. Other comorbidities were less than 10%. It seems that these rates are also found with other common conditions and is not supporting the idea that more comorbidities increase the risk of symptomatic COVID-19 unless hypertension is present.
Other systematic reviews that included limited studies in the beginning of this outbreak reported the same finding about accompanying hypertension as the most prevalent risk to symptomatic COVID-19 infection. Although other reports have noted accompanying of different comorbidities such chronic liver, kidney, heart and even lung diseases, we presume that the comorbidities only cause the patients refer more to the hospital, but the comorbidities do not seem to be the cause of disease severity or even mortality. There is limited data about smoking as an influencing factor on the severity of the disease. Thus so far, we cannot make any conclusion, but obviously smoking recession improves airway clearance.
COVID-19 infection seems to be affecting every race, sex, age, irrespective of health status. The risk of symptomatic and severe disease might be higher due to the higher age which is usually accompanied with comorbidities. However, comorbidities do not seem to be the prerequisite for symptomatic and severe COVID-19 infection, except hypertension.
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