COVID-19 Comorbidities: How Do Underlying Hypertensive and

Cardiovascular Conditions Affect the Prognosis and Therapies of

COVID-19?

Huiyi Xiong

Biomedical Engineering, Boston University, Boston, MA, 02215, U.S.A.

Keywords: COVID-19, Underlying Comorbidities, Cardiovascular System.

Abstract: The coronavirus disease 2019 (COVID-19), a contagious disease caused by the SARS-CoV-2 virus, spread

worldwide in a short period and affected the lives of billions of people. Recent studies have found that many

COVID-19 patients have underlying comorbidities that lead to acute disease prognosis and more severe

complications of COVID-19 symptoms. Among all common comorbidities, hypertension and cardiovascular-

related diseases appear more frequently in patients. In this review, we investigate the bidirectional interaction

between COVID-19 and the cardiovascular system by clarifying the effects of SARS-CoV-2 infection on

underlying hypertension conditions and cardiovascular disorders and how hypertension and cardiovascular

diseases affect the mortality and prognosis COVID-19. Combined with analysis of promising but currently

controversial remedies for COVID-19, such as anti-hypertensive therapies that use ARBs and ACE inhibitors

and other treatments of acute COVID-19 cardiovascular syndrome, we could better understand the

interactions between SARS-CoV-2 virus and hypertensive-cardiovascular related comorbidities to develop

safer and more effective treatments for COVID-19.

1 INTRODUCTION

COVID-19 is a contagious disease caused by SARS-

CoV-2. Researchers have found that SARS-CoV-2

has numerous similar biological characteristics to

SARS-CoV, which caused the 2002 outbreak. SARS-

CoV-2 binds the viral spike protein to ACE2 for cell

entry into human bodies (Allen, Altae-Tran, Briggs,

Jin, McGee, Shi, Lin, Bansal, Bosso, Thanaraj, Abu-

Farha, Alanbaei, Abubaker, & Al-Mulla 2020)

Comorbidities increase the severity of COVID-19

symptoms, prolong the viral clearance time, and

deteriorate acute disease prognosis, thus leading to

more severe forms and complications of COVID-19

in patients (De Cauwer, Ejaz, Alsrhani, Zafar, Javed,

Junaid, Abdalla, Younas, Esakandari, Nabi-Afjadi,

Fakkari-Afjadi, Farahmandian, Miresmaeili, &

Bahreini, Fang, Karakiulakis, & Roth 2020). Among

these factors, we found that hypertension and

cardiovascular diseases are associated with cardio-

cerebrovascular systems. The exceeding frequency of

COVID-19 patients with hypertension and

cardiovascular diseases implies the crucial role they

https://orcid.org/0000-0003-1449-3996

played in the prognosis of COVID-19 patients and

thus need to be investigated comprehensively.

This review will collect common comorbidities

found by various studies and evaluate the substantial

incidence of COVID-19. We will investigate the

mechanisms of how the SARS-CoV-2 virus affects

hypertension and cardiovascular conditions of

patients. The impacts of underlying hypertension and

cardiovascular diseases on the progression and

prognosis of COVID-19 will be collected as well,

especially factors that affect the morbidity and

mortality of COVID-19 (Fox, Akmatbekov, Harbert,

Li, Quincy Brown, & Vander Heide 2020), we also

analyze current treatments toward COVID-19 induced

comorbidities in line with ACE2 expression

mechanism. There are debates about whether using

RAAS inhibitors (ARBs and ACEI) in COVID-19

patients is effective, with some studies claiming they

could alleviate inflammatory responses (Fujihashi, &

Jones 2020) while other studies were arguing that they

would rise the severity of COVID-19 symptoms

instead (Garg, Kim, Whitaker, O'Halloran,

Cummings, Holstein, Fry 2020). The treatments

toward acute myocardial injury, a representative acute

584

Xiong, H.

COVID-19 Comorbidities: How Do Underlying Hypertensive and Cardiovascular Conditions Affect the Prognosis and Therapies of COVID-19?.

DOI: 10.5220/0011515700003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 584-590

ISBN: 978-989-758-596-8

respiratory syndrome associated with high mortality

of hospitalized COVID-19 patients, are also

investigated to show that current treatments toward

COVID-19 induced comorbidities involve complex

factors, and the efficacy of many treatments are still

uncertain.

2 COVID-19 CLINICAL

CHARACTERISTICS

COVID-19 patients could report various symptoms

ranging from mild symptoms to severe illness and

even death. COVID-19 symptoms usually begin

between 2 and 14 days after being infected, and the

incubation period is estimated to be approximately 5

days after exposure to the SARS-CoV-2 virus, similar

to SARS (Garg, S). The virus can be spread to others

from someone infected with the coronavirus but is in

the pre-symptomatic or asymptomatic state (Gasmi,

Peana, Pivina, Srinath, Gasmi Benahmed, Semenova,

Menzel, Dadar, & Bjørklund 2021, Gold, Guo, Fan,

Chen, Wu, Zhang, He, Lu 2020).

According to information from CDC as shown in

Figure 1, it would be necessary to seek emergency

medical attention if patients manifest severe

symptoms, (Guo, Fan, Chen, Wu, Zhang, He, Lu

2020, Hancox, Hasnain, Vieweg, Crouse, &

Baranchuk 2013). Based on 3,661,716 total responses

about COVID-19 symptoms collected in the United

States, the common symptoms reported by most users

(73%) (Hendren, Drazner, Bozkurt, & Cooper 2020).

Figure 1. The systemic disorders caused by COVID-19

(Lauer, Grantz, Bi, Jones, Zheng, Meredith, Lessler 2020).

COVID-19 could be especially life-threatening to

older adults and young children. The severity of

COVID-19 varies dramatically for patients of

different ages. Age as a risk factor seems to be

independent of common comorbidities (Liu, Huang,

Xu, Yang, Qin, Cao, Jiang 2020). Additionally, old

adults with severe underlying medical conditions

seem to have higher risks of developing more serious

COVID-19 symptoms (Hancox, Hasnain, Vieweg,

Crouse, & Baranchuk 2013). Children infected with

COVID-19 usually have a milder illness than adults.

Additionally, these children may also tend to

experience very rare complications of the

coronavirus, such as having abdominal symptoms

like skin changes or rashes (Maragakis 2021).

3 PROFILE OF COMORBIDITIES

Current studies have revealed that the severity of

COVID-19 is highly related to comorbidities (Mayo

Clinic Staff 2021). Comorbidities contribute to acute

disease prognosis, and increased risk of severe

symptoms and more comorbidities were found in

severe cases compared to non-severe cases (Bosso,

Thanaraj, Abu-Farha, Alanbaei, Abubaker, & Al-

Mulla 2020). In a research study, over 50% of

patients reported having at least one comorbidity,

and around 70% of ICU patients have been observed

to have comorbidities (De Cauwer 2020). Another

study conducted among 178 adult patients about

underlying conditions shows that 89.3% of patients

had one or more underlying conditions (McGonagle,

Plein, O'Donnell, Sharif, & Bridgewood 2020). To

be specific, different types of comorbidities need to

be investigated.

A study among 225 patients with severe COVID-

19 symptoms who were hospitalized in eight Georgia

hospitals during March 2020 reported comorbidities

including hypertension (67.5%), diabetes (39.7%),

cardiovascular disease (25.6%), chronic lung disease

(20.3%), severe obesity (BMI ≥40, 12.7%) (Mayo

Clinic Staff 2021).

The percentage of each type of

comorbidity is shown in Figure 2. These studies

show that hypertension, obesity, and cardiovascular

diseases are the top 3 comorbidities of COVID-19.

We have noticed that two of the three most common

commodities are related to a heart condition and

blood pressure (Meng, Xiao, Zhang, He, Ou, Bi,

Zhang 2020). This suggests that people with

preexisting high blood pressure may be at higher risk

of becoming severely ill with COVID-19 and may

induce further hypertensive heart conditions and

high blood pressure. The exceeding frequency

implies a causal relationship between hypertension

and COVID-19, leading to more severe

complications of COVID-19 in patients (Mueller,

McNamara, & Sinclair 2020). Therefore, this review

will mainly focus on hypertension and

cardiovascular problems, investigating how the

SARS-CoV-2 virus interacts with these underlying

COVID-19 Comorbidities: How Do Underlying Hypertensive and Cardiovascular Conditions Affect the Prognosis and Therapies of

COVID-19?

585

conditions and how these conditions impact the

progression and prognosis of COVID-19 (Muhamad,

Ugusman, Kumar, Skiba, Hamid, &amp, Aminuddin

2021).

Figure 2. Common comorbidities associated with COVID-19 infection collected from clinical outcomes of adult patients

hospitalized in Georgia (Mayo Clinic Staff 2021).

4 THE MECHANISM OF

COVID-19-INDUCED

DETERIORATION OF

HYPERTENSION AND

CARDIOVASCULAR DISEASE

The mechanisms underlying this interaction need to

be figured out to clarify the bidirectional interaction

between COVID-19 and the cardiovascular system.

Figure 3 shows how COVID-19 interacts with

underlying comorbidities and leads to cardiovascular

complications.

Figure 3. Bidirectional interaction between cardiovascular

diseases and COVID-19 (Allen, Altae-Tran, Briggs, Jin,

McGee, Shi, Lin 2020).

67,50%

39,70%

25,60%

20,30%

12,70%

0,00%

10,00%

20,00%

30,00%

40,00%

50,00%

60,00%

70,00%

80,00%

hypertension diabetes cardiovascular

disease

chronic lung

disease

obesity

COVID-19 Comorbidities in 225 COVID-19

patients in Georgia Hospitals

ICHIH 2022 - International Conference on Health Big Data and Intelligent Healthcare

586

The mechanisms and pathophysiology underlying

the development of COVID-19-related

cardiovascular injury are currently unclear, but

ACE2, a surface protein for SARS-CoV-2 virus entry

and part of RAAS, is known to be a significant factor

involved in the biological mechanism of COVID-19

infection (Nishiga, Wang, Han, Lewis, & Wu 2020).

It would be possible that SARS-CoV-2 could directly

infect multiple cardiovascular cell types. However,

since the expression of ACE2 in itself is not sufficient

for the virus to enter the cell, the interaction is more

likely to affect the cardiovascular system in an

indirect manner (Allen, Altae-Tran, Briggs, Jin,

McGee, Shi, Lin 2020).

The factors that trigger the impact of the SARS-

CoV-2 virus on hypertension conditions are

controversial. Some studies mentioned that that

originally target the Renin-Angiotensin System

(RAS) for anti-hypertensive purposes. In certain

studies, they are demonstrated to increase ACE2

expression and thus increase the severity of COVID-

19 symptoms (Garg, Kim, Whitaker, O'Halloran,

Cummings, Holstein, Fry 2020). In contrast, in other

studies, the use of ACEi/ARB drugs attenuates

inflammatory responses of COVID-19 patients by

inhibiting IL-6 cytokine levels (Osibogun, Balogun,

Abayomi, Idris, Kuyinu, Odukoya, Akinroye,

Pettersson, Manley, & Hernandez 2021).

5 IMPACTS OF HYPERTENSION

AND CARDIOVASCULAR

DISEASES CONDITIONS ON

THE PROGNOSIS OF

COVID-19

Many studies evaluating COVID-19 prognosis

demonstrated that cardiovascular diseases and

hypertension conditions significantly increase the

severity and mortality rate of COVID-19 patients

(Garg, Kim, Whitaker, O'Halloran, Cummings,

Holstein, Fry 2020). The impacts could be best

manifested in mortality rate data (Preventing the

spread of the coronavirus. 2021). Accordingly, the

case fatality rate (CFR) was also significantly higher

for patients with hypertension and CVD (Meng, Xiao,

Zhang, He, Ou, Bi, Zhang 2020). Additionally, a

research study suggested that hypertension and

cerebro-cardiovascular diseases could be critical

factors that lead to the higher mortality of COVID-19

patients.

To evaluate factors that cause the high mortality

rates for COVID-19 patients with hypertension and

cerebro-cardiovascular diseases, Sharon Fox el. from

the Lancet Respiratory Medicine demonstrates that

the high mortality rates could be attributed to severe

lung involvement, diffuse alveolar damage, and

pulmonary tissue destruction (Public Health Agency

of Canada. 2021). The infected alveolar ACE2+

(angiotensin-converting enzyme 2) cells with

extensive pulmonary vasculature lead to pulmonary

hypertension development due to a pulmonary

intravascular coagulopathy. Therefore, ACE2

expression on endothelial cells could cause virally

mediated endothelins linked to increased mortality

(Riphagen, Gomez, Gonzalez-Martinez, Wilkinson,

& Theocharis, Ruan, Yang, Wang, Jiang, & Song,

Sanyaolu, Okorie, Marinkovic, Patidar, Younis,

Desai, Altaf 2020). In another study in the scope of

150 patients, 32% of patients were reported to have

an acute myocardial injury with heart failure as a

contributing factor (Schiffrin, Flack, Ito, Muntner, &

Webb 2020). These data demonstrate that pulmonary-

related diseases and acute myocardial injury could be

the commonly observed complications leading to the

higher mortality of COVID-19 patients with

hypertension and cardiovascular diseases.

Some studies use the cardiac troponin T level as a

predictive prognosis parameter (Shi, Qin, Shen, Cai,

Liu, Yang, Huang 2020). Combined with other

studies, acute myocardial injury is an essential factor

in the death of COVID-19 patients, and the markers

of myocardial injury could be used to predict the risk

of in-hospital mortality in patients with severe

COVID-19.

6 TREATMENTS TOWARD

COVID-19 INDUCED

COMORBIDITIES

Among widely known treatments, many targeted the

mechanism of the interaction between SARS-CoV-2

virus and ACE2 molecules to alleviate hypertension-

related COVID-19 symptoms. Combined with other

studies that revealed the elevated expression of ACE2

in blood samples from COVID-19 patients

(Symptoms of covid-19. (2021), Turner, Hiscox, &

Hooper 2004, Wan, Shang, Graham, Baric, & Li

2020). While ACEIs/ARBs are proven to be effective

in preventing and treating COVID-19 infections in

some animal studies, limited clinical data in humans

could show that ACE-inhibitors or ARBs affect the

severity of COVID-19 patients with CVD

comorbidity, either improve or deteriorate (Wu, &

McGoogan 2020). By contrast, another retrospective

COVID-19 Comorbidities: How Do Underlying Hypertensive and Cardiovascular Conditions Affect the Prognosis and Therapies of

COVID-19?

587

study was conducted among 511 COVID-19 patients

with hypertension comorbidity to compare the

severity of SARS-CoV-2 infection for those who used

one of the anti-hypertension drugs and those who

used none (Yang, Tan, Zhou, Yang, Peng, Liu, He

2020). The implication of this study recommends

using treatments with ACEI and ARBs are

continuously in patients with hypertension or CVD to

reduce the morbidity and mortality of SARS-CoV-2

infection, especially in elderly COVID-19 patients

(Fujihashi, & Jones 2020). Therefore, anti-

hypertensive therapies such as ARBs or ACEI could

be a possible solution to COVID-19 patients with

hypertensive-related comorbidities, but the efficacy

and potential effects still need further investigation.

Figure 4. ACE2 in the Entry of SARS-CoV-2 into the Host Cell and the function of ACEi and ARBs to reduce SARS-CoV-

2 viral entry (Pettersson, Manley, & Hernandez 2021).

Besides treatments that aim to reduce

hypertension-related comorbidities exacerbated by

the SARS-CoV-2 virus, other treatments focused on

managing the acute COVID-19 cardiovascular

syndrome (Allen, Altae-Tran, Briggs, Jin, McGee,

Shi, Lin 2020). Due to the contagious nature of

COVID-19, the priorities in the diagnosis stage

include reducing staff/patient exposures by limiting

testing and patient transfer to avoid the delay of

diagnostic procedures, though this would reduce the

certainty of diagnosis. Therefore, it is essential to

minimize the staff/patient exposure for testing while

not changing clinical management that recognizes

syndromes when the most effective intervention.

One focus among acute respiratory syndromes

would be an acute myocardial injury, the comorbidity

that appears to complicate the symptoms of

hospitalized patients and is associated with high

mortality, as mentioned in the earlier paragraph

(Ruan, Yang, Wang, Jiang, & Song 2020). In some

cases, patients diagnosed with myocarditis relating to

COVID-19 were treated with extracorporeal

membrane oxygenation, steroids, intravenous

immunoglobulins, and antiviral therapy and

subsequently recovered.

Treatments need to vary according to the special

situations of patients. In multiple COVID-19 clinical

studies, Hydroxychloroquine and azithromycin,

drugs that show improved clinical recovery time,

body temperature recovery time, cough remission

time, and pneumonia-related symptoms compared to

traditional treatments, are also known to induce

arrhythmias, prolong the QT interval, and more likely

to have cardiac arrest (Allen, Altae-Tran, Briggs, Jin,

McGee, Shi, Lin, Zeng, Liu, Yuan, Wang, Wu, Li,

Liu, Zhang, Dong, Cao, Yuan, Yang, Yan, Gao

2020). Another drug combination Lopinavir–

ritonavir, should be carefully used in COVID-19

patients (Allen, Altae-Tran, Briggs, Jin, McGee, Shi,

Lin 2020). In sum, acute COVID-19 cardiovascular

syndrome management needs to consider complex

factors (Ruan, Yang, Wang, Jiang, & Song 2020).

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588

7 CONCLUSIONS

Current studies have revealed that comorbidities and

underlying conditions are strongly associated with the

severity of COVID-19 symptoms, contributing to

more acute disease prognosis and increased risk of

severe symptoms. Among the most influential

comorbidities, hypertension and cardiovascular

diseases appear with exceeding frequency in COVID-

19 patients. The interaction between the expression of

ACE2 protein and the SARS-CoV-2 virus is a

significant factor involved in the biological

mechanism of COVID-19 viral entry and infection

and then affects the cardiovascular system.

Hypertension and cardiovascular diseases also impact

the progression and prognosis of COVID-19, which

are manifested in higher mortality rates and longer

viral clearance time. Major factors contributing to

high mortality rates of COVID-19 patients with

cardiovascular conditions include pulmonary tissue

destruction and acute myocardial injury. Potential

remedies for COVID-19 include ARBs (angiotensin

II receptor blockers) or ACE (angiotensin-converting

enzyme) inhibitors, which are anti-hypertensive

therapies, but the efficacy and further effects of these

treatments are still controversial. Other treatments

that focus on the management of the acute COVID-

19 cardiovascular syndrome, especially for acute

myocardial injury, need to vary according to different

situations of patients and consider complex factors.

Some treatments of COVID-19 have some known or

unknown cardiovascular adverse effects to be

noticed. Learned from imperfections of current

COVID-19 treatments, researchers may have a

clearer direction of drug development that improves

efficacy while reducing side effects.

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