Introduction
The COVID-19 pandemic has involved millions of people and had thousands of victims globally. To the moment of writing this paper (May 5th, 2020), 4,894,278 cases and 320,189 deaths were reported [
1]. COVID-19 infection is caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), a member of coronaviridae family, believed to able to spread to human from reservoirs like bats [
2].
Due to their large genome, members of coronaviridae family have a great potential to initiate new epidemics as a result of gene mutation. This family of viruses is morphologically known by a crown like protein spike on their envelope [
3].
While common symptoms of COVID-19 infection which are cough, fever, fatigue and myalgia can be seen after about 5 days of incubation period, uncommon symptoms such as dyspnea, chest pain, chest tightness, diarrhea and vomiting can also be seen during the time course of infection [
3‐
12].
The main causes of death in COVID-19 infection are acute respiratory distress syndrome (ARDS), renal and cardiac failure [
13]. Global mortality rate of COVID-19 infection is estimated about 6%(5.7%) [
7].
It is acknowledged that people with comorbidities are at a greater risk of getting infected with SARS-CoV-2 and developing severe disease. Hypertension is the most common comorbidity among COVID-19 patients which is accompanied by higher risk of infection and worse outcomes and prognosis [
13‐
18]. The fact that hypertension is the most common comorbidity in COVID-19 patients is not a great surprise because the frequency and severity of the infection is higher in elderly and hypertension is seen frequently in old individuals and as a result, hypertension can be seen in a lot of COVID-19 cases. However it remains unclear whether uncontrolled blood pressure is a risk factor for getting infected with COVID-19 and developing severe disease or not [
18].
A meta-analysis demonstrated that patients with underlying cardiovascular disease like hypertension are more susceptible to MERS-CoV infection [
19] and some studies have shown that patients with cardiovascular disease especially hypertension are at a greater risk for getting infected with COVID-19 and developing more severe disease but further investigations are needed in this area [
20].
Although hypertension is the most common comorbidity among COVID-19 patients and some studies have shown its association with worse outcomes [
13‐
16,
18], there in not enough data available about prognostic factors among COVID-19 patients with underlying hypertension to predict possible outcomes among them, So in the present study we aimed to evaluate epidemiologic, clinical and laboratory differences between COVID-19 patients with and without underlying hypertension and came up with some prognostic factors to predict the severity of the disease and other possible outcomes among patients with pre-existing hypertension.
Results
In this study, 598 medical profiles of COVID-19 patients were analyzed. 176(29.4%) patients were hypertensive and 422(70.6%) were normotensive. Mean age was 58.21 ± 22.5 in hypertensive group and 56.21 ± 20.2 in normotensive group (
P-value: 0.18). 115(65.3%) patients in hypertensive group and 289(68.5%) patients in normotensive group were men (
P-value:0.78). Diabetes was seen more in hypertensive group.72(40.9%)hypertensive patients and 76(18%) normotensive ones were diabetic which was statistically significant(
P-value:0.001). Cardiovascular disease was significantly higher in hypertensive group[63,(35.7%)] in comparison to normotensive group[44(10.3%)] (
P-value:0.001). Renal disorders were significantly higher in hypertensive group [25(14.3%)]vs.[33(7.8%)] respectively (P-value:0.013). Severe/critical types were significantly higher in hypertensive group comparing to normotensive one, [42(23.8%) vs 41(9.7%)], (
P-value:0.012). No significant difference was seen in other variables (history of exposure to COVID-19 patients in past 2 weeks, smoking, brain stroke, respiratory disease, cancer(P-value > 0.05), (Table
1).
Table 1
Comparison of demographic characteristics of patients with COVID-19 in two groups (hypertensive and normotensive patients)
Age (Year) | 58.21 ± 22.5 | 56.15 ± 20.2 | 0.18 |
BMI (kg/m2) | 28.62 ± 4.6 | 28.01 ± 4.3 | 0.13 |
Sex (male) | 115(65.3%) | 289(68.5%) | 0.78 |
Education | | | 0.65 |
• < diploma | 57 (32.4%) | 111(26.3%) | |
• >Diploma | 119(67.6%) | 311 (73.7%) | |
Exposure history | 30(17%) | 191 (45.2%) | 0.45 |
• Contact with patients | 118(67%) | 250 (59.2%) | 0.061 |
• Go hospital | 30(17%) | 87(20.6%) | 0.23 |
• Public transportation | 24(22.5%) | 118(24.1%) | 0.64 |
Comorbidities (positive) | 108(61.3%) | 249(59%) | 0.75 |
Current smoker | 4(2.2%) | 12(2.8%) | 0.92 |
Diabetes | 72(40.9%) | 76(18%) | 0.001 |
CVD | 63(35.7%) | 44(10.3%) | 0.001 |
MI | 4(2.3%) | 2(0. 5%) | 0.061 |
Lung diseases | 36(20.4%) | 52(12.3%) | 0.07 |
Asthma and Allergy | 31(17.6%) | 67 (15.9%) | 0.45 |
Kidney diseases | 25(14.3%) | 33(7.8%) | 0.013 |
Liver diseases | 10(5.7%) | 22(5.2%) | 0.47 |
Cancer | 4(2.3%) | 8(1.9%) | 0.68 |
Blood Group |
• A | 55(31.3%) | 139(32.8%) | 0.21 |
• B | 45(25.5%) | 110(26.3%) | 0.71 |
• AB | 21(11.9%) | 60(14.2%) | 0.52 |
• O | 55(31.3%) | 113(26.7%) | 0.31 |
Clinical type of COVID- 19 infection on admission |
Severe/Critical type (%) | 42(23.8%) | 41(9.7%) | 0.012 |
Clinical and laboratory features and clinical outcome
Univariate analysis showed that the number of patients with high fever (> 38.5) were significantly higher in hypertensive group [75(44.3%)] in comparison to normotensive one [125 (9.6%)], (P: 0.042). Similar results were observed about Dyspnea; [22(12.5%) vs. 20(4.5%)] (P: 0.023).
CT-scan findings showed that unilateral involvement was significantly lower in hypertensive group [25(14.2%)] in comparison with normotensive group [86(20.3%)], (
P value 0.046). However no significant difference was seen in bilateral pulmonary involvement, multiple mottling and ground glass opacity between study groups (
P > 0.05). Other clinical symptoms and laboratory results didn’t show significant difference between two groups (Table
2).
Table 2
Comparison of clinical symptoms, laboratory findings and clinical outcomes of patients with COVID-19 in two groups (hypertensive and normotensive patients)
Fever | N (%) | | | 0.042 |
• ≥38.5 c | | 78(44.3%) | 125(29.6%) | |
• < 38.5 | | 98(45.7%) | 300(70.4%) | |
Cough | N (%) | 103 (58.5%) | 257(60.9%) | 0.38 |
Dysphonia | N (%) | 105(59.6%) | 261(61.8%) | 0.37 |
Chest pain | N (%) | 38(21.6%) | 107(25.3%) | 0.19 |
Dizziness | N (%) | 19(10.7%) | 56(13.2%) | 0.18 |
Headache | N (%) | 56(31.8%) | 153(36.2%) | 0.18 |
Weakness | N (%) | 90(51.4%) | 232(55.1%) | 0.24 |
Rhinorrhea | N (%) | 20(11.3%) | 41(9.7%) | 0.3 |
Myalgia | N (%) | 62(35.2%) | 154(36.5%) | 0.61 |
Test Sense | N (%) | 21(11.9%) | 51(12%) | 0.91 |
Shortness of breath | N (%) | 22(12.5%) | 20(4.7%) | 0.023 |
Diarrhea | N (%) | 34(19.3%) | 84(19.9%) | 0.76 |
Vomiting | N (%) | 53(30.2%) | 136(32.3%) | 0.23 |
Laboratory tests |
Leucocytes (× 109/L) | 4–10 | 7.61 ± 7.45 | 6.26 ± 3.08 | 0.14 |
Neutrophils (×109/L) | 2–7 | 6.28 ± 0.65 | 5.23 ± .065 | 0.12 |
Lymphocytes (×109/L) | 0.8–4 | 2.09 ± 1.68 | 2.06 ± 1.68 | 0.31 |
Platelets (×109/L) | 125–450 | 164.2 ± 63.1 | 159.6 ± 75.2 | 0.12 |
Hemoglobin (g/L) | 115–150 | 15.67 ± 2.7 | 14.8 ± 2.8 | 0.068 |
Hematocrit (%;) | 33.35–50.8 | 44.15 ± 3.7 | 42.1 ± 4.3 | 0.23 |
Albumin (g/L) | 40–55 | 44.15 ± 7.8 | 41.5 ± 6.5 | 0.063 |
Alt(U/L) | 9–50 | 40.5 ± 24.6 | 39.6 ± 29.2 | 0.081 |
Ast(U/L) | 15–40 | 36.1 ± 26.2 | 32.2 ± 25.1 | 0.038 |
Total bilirubin) | 0–26 | 9.1 ± 3.1 | 8.6 ± 4.2 | 0.25 |
Serum sodium (mmol/L) | 137–147 | 135.6 ± 15.5 | 134.1 ± 18.1 | 0.71 |
Serum potassium (mmol/L) | 3.5–5.3 | 3.41 ± 2.4 | 3.31 ± 2.9 | 0.77 |
Glucose (mmol/L) | 70–140 | 5.99 ± 2.15 | 5.01 ± 1.96 | 0.62 |
INR | 0.85–1.15 | 1.41 ± 0.17 | 1.15 ± 0.13 | 0.28 |
CRP (mg/L) d | 0–10 | 41.2 ± 32.1 | 39.8 ± 31.2 | 0.11 |
Chest X-ray/CT findings | N (%) | | | |
• Normal | | 19(10.7%) | 50(11.8%) | 0.24 |
• Unilateral pneumonia | | 25(14.2%) | 86(20.3%) | 0.046 |
• Bilateral pneumonia | | 68 (38.6%) | 156(36.9%) | 0.12 |
• Multiple mottling and ground-glass opacity | | 64(36.5%) | 159(31%) | 0.071 |
Clinical outcome |
Increased hospital stays | N (%) | 41(22.9%) | 46(10.9%) | 0.015 |
Death | N (%) | 16(9.1%) | 25(5.9%) | 0.11 |
Readmission | N (%) | 20(11.3%) | 42(9.9%) | 0.28 |
Comparison of clinical outcomes of COVID-19 between our study groups showed that 41(22.9%) of hypertensive and 46(10.9%) of normotensive patients needed longer hospital stay which was statistically significant (
P-value: 0.015). Mortality and need to readmission showed no significant difference between two groups (
P value > 0.05), (Table
2). Cause of death in the current study was severe COVID-19 infection leading to ARDS, cardiac arrest and multi-organ failure.
Prediction of risk factors for severe-critical COVID-19 in patients with and without hypertension
Generally, 23.8% of hypertensive patients developed severe/critical COVID-19. In order to determine independent predictive variables of severe COVID-19 among hypertensive patients, all variables with statistical significance in univariate distribution were included in logistic regression multivariate analysis. This innovative approach showed that body mass index (BMI) > 25 (OR
Adj:1.8, 95% CI:1.2 to 2.42;
P-value: 0.027), age over 60(OR
Adj:1.26, 95% CI:1.08 to 1.42; P-value: 0.021), increased hospitalization period (OR
Adj:2.1, 95% CI:1.24 to 2.97; P-value: 0.013), type 2 diabetes (OR
Adj:2.22, 95% CI:1.15 to 3.31; P-value: 0.001) and chronic kidney disease (OR
Adj:1.83, 95% CI:1.19 to 2.21; P-value: 0.013) were the significant independent risk factors of severe COVID-19 in hypertensive patients (Table
3). Notably, after performing the same model on the cases without hypertension, it was revealed that only older age was associated with a higher risk of sever disease among these group participants. Severe/critical COVID-19 infection was significantly higher among hypertensive group. Besides, we showed that None of the other risk factors mentioned above (BMI > 25 Kg/m2, CVD, diabetes and chronic kidney disease) are statistically significant among normotensive group. As a result, we can mention hypertension as a risk factor to develop severe COVID-19 infection.
Table 3
Multivariate logistic Regression of Factors Associated with Progression of disease in patients with and without hypertension
Age>60year-old | 1.26 | 1.08-1.46 | 0.021 | 1.06 | 011. -2.08 | 0.044 |
BMI>25(kg/m2) | 1.8 | 1.02–2.42 | 0.027 | 1.34 | 0.88–1.89 | 0.21 |
Increased hospital stays (positive) | 2.1 | 1.24–2.97 | 0.013 | 1.48 | 0.36–2.61 | 0.28 |
CVD (positive) | 3.3 | 1.3–5.4 | 0.001 | 2.8 | 0.84–4.78 | 0.058 |
Diabetes (positive) | 2.22 | 1.15–3.31 | 0.001 | 1.24 | 0.59–1.92 | 0.28 |
Kidney daisies (positive) | 1.83 | 1.19–2.21 | 0.013 | 1.22 | 0.66–1.81 | 0.052 |
Discussion
In the present study performed on 598 patients with confirmed COVID-19, 176 (29.4%) patients had underlying hypertension. Using a novel approach, we have showed some important risk factors predictive for developing severe infection among COVID-19 hypertensive patients including Age > 60-year-old, BMI > 25 Kg/m2, CVD, diabetes and chronic kidney disease.
As it is proven before, hypertension is the most common underlying disorder among COVID-19 patients [
25‐
29]. Shi et al., and Guo et al., reported a high prevalence of hypertension (59.8–63.5%), among COVID-19 patients which was accompanied by mortality [
30,
31]. A study conducted by Lippi et at., reported that hypertension carries higher risk of developing severe COVID-19 [
32].
Since hypertension is the most common comorbidity among COVID-19 patients and it has been frequently reported that hypertension increases severity of COVID-19 infection [
25,
27‐
29,
33], a lot of hypertensive people would be worried about ending up with severe COVID-19 infection and poor clinical outcomes, So we have done a completely novel study which can show hypertensive patients the most important risk factors to develop severe COVID-19 among them and tell them should they really be worried about developing severe COVID-19 or not.
There are some studies showing that some laboratory parameters are predictors of worse clinical outcomes in COVID-19 patients. Some of these parameters are cardiac biomarkers, pro-inflammatory cytokines and ferritin [
34]. Moreover, some other clinical predictors have also been reported in early studies such as, old age, male gender, cardiovascular diseases, respiratory diseases and diabetes to be related with severe COVID-19 [
14] but until this moment, there is no data available to specifically show risk factors of developing severe COVID-19 among hypertensive patients.
The reason why hypertensive patients are at a greater risk of severe COVID-19 is unclear. However, a possible theory is that Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus family; SARS-CoV, MERS-CoV and SARS-CoV-2), bind to their target cells through Angiotensin Converting Enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels [
23]. Notably, the underlying hypertension in COVID-19 patients is often treated with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Controlling hypertension with ACE inhibitors and ARBs, results in an up regulation of ACE2 [
35]. Consequently, the increased expression of ACE2 might facilitate COVID-19 infection.
Our novel study reveals predictive factors for developing severe COVID-19 that can be used by physicians to identify high risk hypertensive COVID-19 cases and determine appropriate treatment approach to achieve best possible clinical outcomes.
The only limitation of our study was its retrospective design in which some terms were out of researcher’s control. Further studies in bigger populations and other races are needed to confirm whether our novel predictive factors for developing severe COVID-19 in hypertensive patients can be true about other populations and races or not. Also, all hypertensive patients of this study were receiving anti-hypertensive medications but the data of the exact class of anti-hypertensive medication was not collected.
Conclusion
Although hypertensive patients are at increased risk of developing more severe COVID-19 compared to normotensives, here we came up with some predictive factors to identify patients with poor outcomes in those with COVID-19 infection which are: Age > 60-year-old, BMI > 25 Kg/m2, CVD, diabetes and chronic kidney disorders.
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