key: cord-0961870-hox6xll7
authors: Chen, Liqin; Chen, Jiankun; Wu, Yuwan; Zhong, Jinyao; Zhou, Fuzhen; Liu, Yuntao; Xu, Aiting; Li, Jiqiang; Cai, Huayang
title: Clinical Characteristics and Outcomes of Hypertensive Patients Infected with COVID-19: A Retrospective Study
date: 2021-08-17
journal: Int J Gen Med
DOI: 10.2147/ijgm.s324077
sha: 838a2aae5f2433511af81266fa9e74fab55dc8d8
doc_id: 961870
cord_uid: hox6xll7

BACKGROUND: Hypertension has been reported as the most prevalent comorbidity in patients with coronavirus disease 2019 (COVID-19). This retrospective study aims to compare the clinical characteristics and outcomes in COVID-19 patients with or without hypertension. METHODS: A total of 944 hospitalized patients with laboratory-confirmed COVID-19 were included from January to March 2020. Information from the medical record, including clinical features, radiographic and laboratory results, complications, treatments, and clinical outcomes, were extracted for the analysis. RESULTS: A total of 311 (32.94%) patients had comorbidity with hypertension. In COVID-19 patients with hypertension, the coexistence of type 2 diabetes (56.06% vs 43.94%), coronary heart disease (65.71% vs 34.29%), poststroke syndrome (68.75% vs 31.25%) and chronic kidney diseases (77.78% vs 22.22%) was significantly higher, while the coexistence of hepatitis B infection (13.04% vs 86.96%) was significantly lower than in COVID-19 patients without hypertension. Computed tomography (CT) chest scans show that COVID-19 patients with hypertension have higher rates of pleural effusion than those without hypertension (56.60% vs 43.40%). In addition, the levels of blood glucose [5.80 (IQR, 5.05–7.50) vs 5.39 (IQR, 4.81–6.60)], erythrocyte sedimentation rate (ESR) [28 (IQR, 17.1–55.6) vs 21.8 (IQR, 11.5–44.1), P=0.008], C-reactive protein (CRP) [17.92 (IQR, 3.11–46.6) vs 3.15 (IQR, 3.11–23.4), P=0.013] and serum amyloid A (SAA) [99.28 (IQR, 8.85–300) vs 15.97 (IQR, 5.97–236.1), P=0.005] in COVID-19 patients with hypertension were significantly higher than in patients without hypertension. CONCLUSION: It is common for patients with COVID-19 to have the coexistence of hypertension, type 2 diabetes, coronary heart disease and so on, which may exacerbate the severity of COVID-19. Therefore, optimal management of hypertension and other comorbidities is essential for better clinical outcomes.

The coronavirus disease , caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a public health emergency worldwide. It typically presents with fever, cough, myalgia, and fatigue. As of July 22, 2021, there have been 191,773,590 confirmed cases and 4127,963 deaths, with the numbers still rising across 217 countries/regions worldwide. 1 Therefore, COVID-19 has been considered a pandemic. 2 Previous studies have suggested that the presence of comorbidities among COVID-19 may be associated with poor clinical outcomes. 3 According to the latest reports, around 20-51% of patients with COVID-19 have at least one comorbidity, [4] [5] [6] with hypertension (16.9%) and diabetes mellitus (8.2%) being the most prevalent comorbidities. 7 A pooled analysis has indicated that hypertension may be related to a higher risk of severe or fatal COVID-19, especially in the elderly. 8 The angiotensin-converting enzyme 2 (ACE2) has been discovered to be the receptor that allows the entry of SARS-CoV-2 into human cells. 9 ,10 ACE2 converts angiotensin II to Ang-(1-7), transforming the vasoconstrictor into a vasodilator peptide, which promotes the release of nitric oxide, decreases the outflow of sympathetic nerves, increases baroreflex sensitivity, and ultimately reduces hypertension. 11 However, the relationship between COVID-19 and hypertension remains unclear.

The objective of this study was to elucidate the risk and severity of COVID-19 among patients with comorbid hypertension by investigating the clinical features, radiographic and laboratory results, complications, treatments, and clinical outcomes of COVID-19 patients with or without hypertension.

This was a retrospective study. We included 944 hospitalized COVID-19 patients from the Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to March 2020. All patients confirmed to have COVID-19 using a real-time reversetranscriptase polymerase chain reaction (RT-PCR) assay of the sputum, throat swab, or lower respiratory tract secretion specimens were hospitalized for treatment. All patients were divided into hypertension group and nonhypertension group according to whether they had hypertension or not. Written informed consent was waived owing to the rapid emergence of this infectious disease and the urgent need to collect data.

The demographics, clinical symptoms or signs, radiological and laboratory results, comorbidities, and treatment results were extracted from the electronic medical record system. All medical data reviews and collections were processed by experienced clinicians. We established a computerized database for data storage and verification. Missing or incomplete information was acquired by sending requests for clarification to the coordinators, who subsequently contacted the attending clinicians. Major disagreements during the extraction process were resolved by consultation with the reviewers.

Finally, in accordance with the guidelines for prevention and treatment of hypertension in China (2018 Edition), 12 we divided the patients into two groups: the COVID-19 with hypertension group and the non-hypertensive group (Hypertension was defined as: clinic systolic BP≥140 mmHg and/or diastolic BP≥90 mmHg without the use of antihypertensive medications at three visits on different days; with a BP<140/90 mmHg but having hypertensive history and currently are taking anti-hypertensive medication).

To assess the severity of COVID-19 among the patients with hypertension, the primary clinical outcomes included admission to an intensive care unit (ICU), discharge from the hospital, duration of hospitalization, and death. 13 

Laboratory confirmation of SARS-CoV-2 was performed in accordance with the protocol established by the World Health Organization using RT-PCR assays at Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine. The laboratory confirmation processes were similar to the ones used in our previous study. 14 

Continuous variables are described as mean and standard deviation, and categorical variables are expressed as frequencies and percentages. Continuous variables were analyzed using an independent sample t-test when normally distributed; otherwise, the Mann-Whitney test was used. Categorical variables were compared using the chi-square test or Fisher's exact test. All statistical analyses were performed using Statistical Package for the Social Sciences version 13.0 software (IBM; Chicago, Illinois, United States). Statistical significance was set at P <0.05. .001) were significantly higher among patients with hypertension than among those without. Palpitation (12.50% vs 87.50%, P=0.028) was the only symptom that was statistically different between the two groups. It is possible that hypertensive patients were more likely to regularly take antihypertensive medication, making them less sensitive to palpitations. Table 1 also shows significant differences in the comorbidities between COVID-19 patients with and without hypertension, including diabetes mellitus (56.06% vs 43.94%, P<0.001), coronary heart disease (65.71% vs 34.29%, P<0.001), poststroke syndrome (68.75% vs 31.25%, P<0.001), chronic kidney disease (77.78% vs 22.22%, P=0.007), and hepatitis B infection (13.04% vs 86.96%, P=0.043). However, malignant tumors, chronic obstructive pulmonary disease, asthma, heart failure, arrhythmia, and bronchiectasis were similar between the two groups.

The radiologic indices ( Table 2) showed that 767 (81.25%) of the patients had radiological abnormalities, including 572 cases (64.41%) with ground-glass opacity, 76 (8.56%) with local patchy shadowing, 521 (58.67%) with bilateral patchy shadowing, and 53 (5.97%) with pleural effusion, which are the typical features of an organizing pneumonia pattern of a lung injury. 16 Compared with nonhypertensive patients, hypertensive patients had higher rates of pleural effusion (56.60% vs 43.40%, P < 0.001), which may have resulted from bacterial superinfection or another cause among the hypertensive COVID-19 patients. Table 3 shows the laboratory findings on admission. Blood glucose levels (5.80 

as it has been previously reported that hypoxia could decrease ACE2 expression in the lung tissues of rats. 17 

As shown in Table 4 , 86 patients were admitted to the ICU and 904 patients were discharged from the hospital. There were no significant differences in the incidence of ICU admission and hospital discharge between the two groups.

No deaths were observed during the entire study. The median duration of hospitalization was 14 days (median, 9-20 days 

All COVID-19 patients received symptomatic treatment. The majority of the patients (77.67%) received antiviral therapy, while 61.5% received intravenous antibiotic therapy. Furthermore, 31.31% received systemic glucocorticoids, and 1.44% received antifungal medication. The majority (89.62%) received oxygen therapy, while only a few required invasive (1.52%) and noninvasive mechanical ventilation (7.16%). In addition, 83.93% received traditional Chinese medicine treatment, 69.92% received Chinese patent medicine treatment, and 16.68% received acupuncture or ear acupoint therapy. There were no significant differences in the above treatment measures between the COVID-19 patients with and without hypertension. Anti-hypertensive drugs and lipid-lowering drugs were administered more to patients with hypertension than to those without (62.12% vs 37.88%, P<0.001 and 44.00% vs 56.00%, P<0.036, respectively), whereas antidiabetic drugs were used less frequently in hypertensive patients (44.00% vs 56.00%, P=0.036) ( Table 4) . 

During hospital admission, patients were diagnosed with acute respiratory distress syndrome (5.15%), acute heart failure (1.50%), septic shock (1.07%), acute kidney injury (1.07%), disseminated intravascular coagulation (DIC) (0.21%), and rhabdomyolysis (0.11%). However, all the above-mentioned diagnoses showed similar incidences in the two groups.

Compared to the diseases associated with previous coronavirus epidemics, such as the Severe Acute Respiratory Syndrome and the Middle East Respiratory Syndrome, COVID-19 is more severe and has a faster spread. 18 SARS-CoV-2 enters cells through the ACE2 receptor, considered the functional receptor for this coronavirus. 19 Additionally, ACE2 is regarded as a potent modulator of blood pressure, and its deficiency leads to hypertension. 20 Due to the interaction between SARS-CoV-2 and ACE2, it is believed that hypertension may be related to the pathogenesis of COVID-19 by working directly as a previous clinical predictor of disease severity or by leading to late deterioration in the disease process. 8 Hypertension, diabetes, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease are risk factors for COVID-19. [21] [22] [23] [24] [25] In this retrospective cohort study, we focused on hypertension as it was the most prevalent comorbidity among patients with COVID-19. The median age of the COVID-19 patients was 60 years, and the prevalence rate of hypertension was 32.94%. We found no difference in the patients' sex distribution, but the patients with hypertension were older and had higher blood pressures, consistent with a previous study. 26 This may be due to the higher median age of the patients we included. Normally, the frequency of palpitation is higher in patients with hypertension. However, in our study, the incidence of palpitations was lower in the hypertensive group, which could have resulted from the small number of patients with palpitation or the presence of drug interventions in hypertensive patients. Our study indicated that hypertensive COVID-19 patients had more comorbidities, such as diabetes mellitus, coronary heart disease, pleural effusion, and chronic kidney disease.

Chest CT images proved that patients with hypertension had higher rates of pleural effusion than those without hypertension, indicating that the former had more severe lung pathologies. 27 Furthermore, the levels of the inflammatory markers, such as the erythrocyte sedimentation rate, serum amyloid A, and C-reactive protein, were elevated in the COVID-19 patients, pointing to an increased likelihood of developing cytokine storm in these patients. Furthermore, the levels of these markers were significantly higher in patients with hypertension than in those without hypertension. Integrating these results with the chest CT results above, we can surmise that COVID-19 patients with hypertension were more likely to develop a more severe infection. Hence, patients in the hypertensive group had longer hospital stays than those in the nonhypertensive group. Moreover, there was no significant difference in clinical treatment between the two groups, except for the use of antihypertensive and lipid-lowering drugs.

Our study had the following limitations. First, this study was retrospective and non-randomized. Thus, the clinical outcomes were not as accurate as those in prospective studies. Second, the severity of COVID-19 was not graded. As such, the proportion of patients with each grade could not be determined. Third, due to the outbreak isolation management and lack of equipment, the blood pressure was not measured daily. Fourth, systemic glucocorticoids have been widely used to treat COVID-19 patients, which may influence blood pressure. Therefore, multicenter and prospective studies are necessary to further explore the risk factors and severe events in COVID-19 patients with hypertension.

In conclusion, hypertension worsens the morbidity of COVID-19 patients. This study provided at least two essential lessons for the clinical management of COVID-19. First, controlling blood pressure in COVID-19 patients with hypertension is necessary. Second, increased clinical vigilance is warranted for COVID-19 patients with hypertension, given its chronicity and associated morbidity.

The study was performed in accordance with the Declaration of Helsinki and carried out in accordance with the recommendations of Chinese National Guidelines and Ethics Branch of the Biomedical Ethics Committee of Guangzhou University of Chinese Medicine (ZE2020-049-01). 

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International Journal of General Medicine 2021:14

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The authors are grateful to the doctors and nurses of Hubei Provincial Integrated Traditional Chinese and Western Medicine Hospital for their assistance.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. 

The authors declare no conflicts of interest in relation to this work.