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Aging and disease    2020, Vol. 11 Issue (4) : 874-894     DOI: 10.14336/AD.2020.0520
Review |
Multi-organ Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis
Wu Ting1,2, Zuo Zhihong1,3, Kang Shuntong1,3, Jiang Liping3, Luo Xuan4, Xia Zanxian5,6, Liu Jing1, Xiao Xiaojuan1, Ye Mao7, Deng Meichun1,3,6,*
1Department of Biochemistry and Molecular Biology & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Hunan 410013, China.
2Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
3Xiangya School of Medicine, Central South University, Hunan 410013, China.
4Hunan Yuanpin Cell Biotechnology Co., Ltd, Hunan 410129, China.
5Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China.
6Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410013, China.
7Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
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Abstract  

This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for articles published until May 13, 2020. Two investigators independently selected trials, extracted data, and evaluated the quality of individual trials. Single-arm meta-analysis was performed to summarize the clinical features of confirmed COVID-19 patients. Fixed effects meta-analysis was performed for clinically relevant parameters that were closely related to the patients’ various organ functions. A total of 73 studies, including 171,108 patients, were included in this analysis. The overall incidence of severe COVID-19 and mortality were 24% (95% confidence interval [CI], 20%-28%) and 2% (95% CI, 1%-3%), respectively. Patients with hypertension (odds ratio [OR] = 2.40; 95% CI, 2.08-2.78), cardiovascular disease (CVD) (OR = 3.54; 95% CI, 2.68-4.68), chronic obstructive pulmonary disease (COPD) (OR=3.70; 95% CI, 2.93-4.68), chronic liver disease (CLD) (OR=1.48; 95% CI, 1.09-2.01), chronic kidney disease (CKD) (OR = 1.84; 95% CI, 1.47-2.30), chronic cerebrovascular diseases (OR = 2.53; 95% CI, 1.84-3.49) and chronic gastrointestinal (GI) disease (OR = 2.13; 95% CI, 1.12-4.05) were more likely to develop severe COVID-19. Increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity cardiac troponin I (hs-cTnI), myoglobin, creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were highly associated with severe COVID-19. The incidence of acute organ injuries, including acute cardiac injury (ACI); (OR = 11.87; 95% CI, 7.64-18.46), acute kidney injury (AKI); (OR=10.25; 95% CI, 7.60-13.84), acute respiratory distress syndrome (ARDS); (OR=27.66; 95% CI, 18.58-41.18), and acute cerebrovascular diseases (OR=9.22; 95% CI, 1.61-52.72) was more common in patients with severe COVID-19 than in patients with non-severe COVID-19. Patients with a history of organ dysfunction are more susceptible to severe conditions. COVID-19 can aggravate an acute multiorgan injury.

Keywords COVID-19      multiorgan dysfunction      acute multiorgan injury     
Corresponding Authors: Deng Meichun   
About author:

These authors contributed equally to this work.

Just Accepted Date: 30 May 2020   Issue Date: 30 July 2020
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Wu Ting
Zuo Zhihong
Kang Shuntong
Jiang Liping
Luo Xuan
Xia Zanxian
Liu Jing
Xiao Xiaojuan
Ye Mao
Deng Meichun
Cite this article:   
Wu Ting,Zuo Zhihong,Kang Shuntong, et al. Multi-organ Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis[J]. Aging and disease, 2020, 11(4): 874-894.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.0520     OR
OverallOverall
CFR, % (95%CI)2(1-3)Laboratory results (95%CI)
CSR, % (95%CI)24(20-28)Liver function
Comorbidity, % (95%CI)ALT, U/L27.02(24.67-29.37)
Hypertension19(15-23)AST, U/L30.50(28.09-32.91)
Diabetes10(8-13)Total bilirubin, mmol/L11.10(10.16-12.04)
CVD8(4-14)Renal function
COPD2(2-3)Creatinine, μmol/L69.18(65.22-73.13)
Cerebrovascular diseases3(2-5)Urea mmol/L4.76(4.31-5.22)
CLD3(2-4)Cardiac function
CKD3(1-4)Myoglobin, ng/mL49.96(37.11-62.81)
Tumor3(1-5)CK, U/L84.69(74.51-94.86)
GI disease7(5-8)LDH, U/L275.43(247.82-303.04)
Nervous system disease1(0-2)hs-cTnI, pg/mL13.08(8.22-17.94)
Neurologic symptoms, % (95%CI)CT % (95%CI)
Headache15(9-23)Bilateral involvement of chest radiographs85(78-90)
Dizziness10(7-13)Complications% (95%CI)
Impaired consciousness9(8-10)ARDS12(7-18)
Olfactory and/or taste disorders.54(37-70)ACI6(3-9)
Olfactory disorders28(9-52)Shock6(2-11)
Taste disorders30(12-52)AKI4(1-7)
GI symptoms, % (95%CI)Acute cerebrovascular disease2(1-3)
Anorexia21(14-29)GI symptoms, % (95%CI)
Abdominal pain5(2-10)Nausea7(4-11)
Diarrhea9(6-12)Vomiting5(1-10)
Table 1  Clinical features of COVID-19 cases.
Figure 1.  PRISMA Diagram of Study Selection.
Figure 2.  Relationship between cardiac dysfunction (Hypertension, CVD, CK and LDH) and COVID-19 severity.
Figure 3.  Relationship between cardiac dysfunction (hs-cTnI, myoglobin, ACI and arrhythmia) and COVID-19 severity.
Figure 4.  Relationship between renal dysfunction and COVID-19 severity.
Figure 5.  Relationship between pulmonary dysfunction and COVID-19 severity
Figure 6.  Relationship between liver dysfunction and COVID-19 severity
Figure 7.  Relationship between neurologic dysfunction and COVID-19 severity.
OR/WMD, 95%CI
COVID-19SARSMERS
Cardiac function
HypertensionOR = 2.40; 95% CI, 2.08-2.78OR138 = 2.6; 95% CI, 2.2-3.5
CVDOR = 3.54; 95% CI, 2.68-4.68OR = 7.42; 95% CI, 4.34-12.69OR138 = 3.5; 95% CI, 3.1-4.8
LDH U/LWMD = 140.27; 95% CI, 102.18-178.36WMD = 214.14; 95% CI, 31.09-217.19
CK, U/LWMD = 34.01; 95% CI, 9.46 -58.59WMD = 149.91; 95% CI, 94.03-205.79
Renal function
CKDOR = 1.84; 95% CI, 1.47-2.30OR = 7.82; 95% CI, 3.52-17.38OR138= 2.2; 95% CI, 1.7-4.9
Creatinine, μmol/LWMD = 10.40; 95% CI, 8.07 - 12.72WMD = 10.31; 95% CI, 6.76 - 13.85WMD = 109.92; 95% CI, 21.33 to 198.5
Urea mmol/LWMD = 1.61; 95% CI, 1.26 -1.96WMD = 2.52; 95% CI, 1.26 - 3.78WMD = 7.63; 95% CI, 6.52-8.74
Pulmonary function
SmokerOR=1.61; 95% CI, 1.28-2.02OR=13.04; 95% CI, 2.77-61.46
COPDOR = 3.70; 95% CI, 2.93-4.68OR=9.2; 95% CI, 1.2-70.56OR138 = 3.1; 95% CI, 2.6-4.2
Bilateral involvement of chest radiographsOR=4.65; 95% CI, 2.97-7.34OR=5.85 95% CI, 3.74-9.15OR138 =4.89; 95% CI,1.16-20.47
Liver function
CLDOR = 1.48; 95% CI, 1.09-2.01OR=25.35; 95% CI, 7.37-87.19OR=2.36; 95% CI, 1.09-5.10
ALT, U/LWMD = 7.11; 95% CI, 5.47-8.75WMD = 10.08; 95% CI, 0.89-19.27WMD = -3.07; 95% CI, -11.26-5.11
AST, U/LWMD = 16.10; 95% CI, 14.00-18.20WMD = 23.80; 95% CI, 11.32-36.29WMD = 34.81; 95% CI, -4.39-74.02
Total bilirubin, mmol/LWMD = 2.75; 95% CI, 2.11- 3.40WMD = 6.31; 95% CI, 2.07 - 10.55WMD = 7.09; 95% CI, 2.09-12.09
Table 2  Comparison of impacts of organ function on severity of COVID-19, MERS and SARS.
Figure 8.  Relationship between gastrointestinal dysfunction and COVID-19 severity.
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