Clinical features of COVID-19 patients with comorbid coronary heart disease

1 Background: In addition to the lungs, the coronavirus disease 2019 (COVID-19) also affects 2 multiple organs throughout the body. The relationship between COVID-19 infection and 3 cardiovascular disease, and the mechanisms by which this disease causes damage to the 4 cardiovascular system are unclear. Coronary heart disease (CHD) is one of the common 5 comorbidities of COVID-19, but there is insufficient evidence for its clinical features and impact 6 on clinical outcomes. The aim of this study was to analyze the clinical characteristics of COVID-19 7 patients with comorbid CHD and the possible risk factors for the occurrence of critical illness. 8 Methods: A single-center, retrospective study was conducted to analyze COVID-19 patients 9 admitted to the Sino-French New City Campus of Tongji Hospital in Wuhan, Hubei Province and 10 treated by the Peking University National Medical Assistance Team between January 29 and March 11 10, 2020. Patients testing positive for SARS-CoV-2 viral nucleic acid in nasopharyngeal swab 12 specimens and who had comorbid CHD, were included in the study. Clinical data and laboratory 13 test results of eligible patients were collected, and the factors associated with the occurrence of 14 critical illness among these patients were evaluated. 15 Results: A total of 205 patients were enrolled in this study, including 20 CHD patients and 185 non16 CHD patients. The mean age was 66.7 years. Compared to non-CHD patients, more CHD patients 17 had comorbid hypertension and diabetes (P < 0.05). In terms of laboratory tests, the CHD group did 18 not differ significantly from the non-CHD group in blood routine, blood chemistry, and various 19 inflammatory cytokines. More CHD patients experienced myocardial injury (25% vs 8.1% P < 20 0.031) and CHD patients were more likely to progress to critical illness (40% vs 16.8%P = 0.012). 21 Univariate logistic regression analysis indicated that a history of CHD, occurrence of myocardial 22 injury, high white blood cell (WBC) count, low lymphocyte count, and elevated levels of Cr, ferritin, 23 IL-2R, IL-8 at admission were factors associated with the occurrence of critical illness. Multivariate 24 regression analysis found that a history of CHD(OR=3.529, 95% CI =1.032-12.075, P =0.044), 25 high WBC count(OR=1.289, 95% CI =1.136-1.463, P<0.001) and low lymphocyte count 26 (OR=0.215, 95% CI =0.075-0.616, P =0.004)were independent factors for the occurrence of 27 critical illness among COVID-19 patients. 28 Conclusion: COVID-19 patients with comorbid CHD commonly exhibited myocardial injury and 29 were prone to developing critical illness. Among COVID-19 patients, a history of CHD,high WBC 30 count and low lymphocyte count were independent risk factors for the occurrence of critical illness. 31 Greater attention and vigilance are needed in this regard during clinical practice. 32


1.
A retrospective analysis of the clinical characteristics of patients of early COVID-19 with coronary heart disease. 2. explored possible mechanisms related to the effects of coronary heart disease on the pathogenesis of COVID-19. 3. Revealed coronary heart disease, high white blood cell counts, and low lymphocyte counts are pivotal predictive values for the pathophysiological progression of COVID-19.

Introduction 1
COVID-19 is a type of enveloped beta-coronavirus [1] , and infections mainly affect the respiratory 2 system, giving rise to typical symptoms, such as fever, cough, fatigue and dyspnea. In severe cases, 3 hypoxemia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction may 4 occur [2] . Cardiovascular disease is a common comorbidity of COVID-19. Patients with 5 cardiovascular disease have a higher prevalence of COVID-19, a higher rate of critical illness, and 6 a higher mortality rate. However, the underlying mechanisms for this phenomenon are unclear [3,4] . 7 In this study, the clinical characteristics and risk factors for critical illness among COVID-19 8 patients with coronary heart disease were analyzed to provide a basis for the early identification 9 and diagnosis of high-risk patients. 10 11

Methods 12
A retrospective analysis was performed on COVID-19 patients admitted to the Sino-French New 13 City Campus of Tongji Hospital in Wuhan, Hubei Province and treated by the Peking University 14 National Medical Assistance Team between January 29 and March 10, 2020. 15 16

Data Collection 17
After patients were admitted to the hospital, their complete medical history was recorded, and 18 measurements of their vital signs and blood oxygen saturation without oxygen inhalation were 19 taken. The patients were then divided according to their condition into mild, normal, severe, and 20 : hs-cTnI increase above the 99 th percentile upper reference limit, i.e. hs-cTnI > 4.2 pg/mL. 38 All patients were routinely tested for SARS-CoV-2 viral nucleic acid using nasopharyngeal or oral 39 swabs. 40 41

Inclusion and exclusion criteria 42
Inclusion criteria were as follows: 1. aged 18 years and over; 2. patients diagnosed with 43 COVID-19 based on the criteria described in the "Diagnosis and Treatment Protocol for 44 COVID-19 (Trial Version 7)"; 3. collection of a complete medical history. 45 Exclusion criteria were as follows: 1. patients who failed to complete tests of myocardial injury 46 markers or inflammatory cytokines; 2. pregnant women; 3. patients with severe concomitant 47 autoimmune diseases, hematological diseases or malignant tumors. 48 49

Statistical analysis 50
Statistical analysis was performed using SPSS 23.0. Categorical data were expressed as a 51 percentage or ratio. Between-group comparisons were performed using Pearson's chi-squared test 52 or Fisher's exact test. Continuous data with a normal distribution were expressed as the mean ± 53 standard deviation. Continuous data with a non-normal distribution were expressed as the median 54 (interquartile range, IQR). Between-groups comparisons were performed using an independent 55 sample t-test or Mann-Whitney U tests. Univariate and multivariate logistic regressions were 56 performed for risk factor analysis, and the results were expressed using the odds ratio (OR) and 95% 57 confidence intervals (CI). P < 0.05 was considered statistically significant. 58

Results 60
A total of 205 patients were included in this study; 20 had coronary heart disease (CHD) and 185 61 were non-CHD patients. The mean age was 66.7 years. The basis for diagnosing a history of CHD 62 was as follows: 1. past coronary angiography or coronary CT showing coronary stenosis of more 63 than 50%; 2. past clinical symptoms of typical angina; 3. a clear history of acute myocardial 64 infarction or old myocardial infarction. 65 The mean medical history of the 20 CHD patients was 7.7 years. One patient had myocardial 66 bridging of the coronary artery, and seven patients had previously undergone percutaneous 67 coronary intervention (PCI, one patient had undergone PCI twice). The specific concomitant 68 symptoms are shown in Table 1 Thirteen patients regularly used secondary preventive medication for CHD before admission, of 73 whom 10 patients were treated with aspirin or clopidogrel antiplatelet therapy alone and 3 patients 74 were treated with aspirin combined with clopidogrel antiplatelet therapy; 3 patients were treated 75 with lipid-lowering drugs alone, 3 patients were treated with traditional Chinese medicine 76 (TCM)/TCM preparations (Sanqi powder, Wenxin granules, or Baoxin pills), and 1 patient did not 77 take medications regularly. 78 If patients were not contraindicated for antiplatelet drugs after admission, they continued to 79 receive secondary preventive medication for CHD regularly, and close monitoring of their 80 electrocardiogram (ECG), vital signs and whether they exhibited symptoms related to myocardial 81 ischemia, such as chest tightness and chest pain, was performed. Seven patients experienced chest 82 tightness and precordial discomfort during their hospital stay. Three patients complained that their 83 symptoms had worsened significantly compared to before admission. Patients were divided into the CHD and non-CHD groups for analysis, which revealed that more 91 CHD patients had comorbid hypertension and diabetes (P < 0.05). In terms of laboratory tests, the 92 CHD group did not differ significantly from the non-CHD group with respect to blood routine, 93 blood chemistry and various inflammatory cytokines. More CHD patients experienced myocardial 94 injury (P < 0.001) and CHD patients were more likely to progress to critical illness (P = 0.012) 95 (