Infectious Disease Expert Calls for Distinct Treatment Strategies for Heart Patients with COVID-19
Professor Kim Sung-Han Highlights Importance of Non-Pharmaceutical Interventions for COVID-19 Prevention, Vaccine Development for Herd Immunity.
The spread of the novel coronavirus (COVID-19) - known to worsen the prognosis for patients with cardiovascular and heart disease - should be deterred with non-pharmaceutical interventions until the development of a proven vaccine or antiviral, an infectious disease expert said.
In an interview with summitMD, Professor Kim Sung-Han from Asan Medical Center, Infectious Diseases, Hematologic Cancer & BMT center outlined the problems of ICU bed shortages and potential risks to health care professionals during the pandemic while stressing that until vaccines or antivirals are available, use of personal protective equipment (PPE) and differentiated treatment strategies can save lives.
Large Number Of COVID-19 Patients with Underlying Cardiovascular Disease
Kim pointed towards several reports from the field that observed many COVID-19 patients had underlying cardiovascular conditions.
A study from Wuhan, China1 on 191 patients showed that 48 percent of all patients had comorbidity. Researchers found 30 percent of all patients had hypertension (48 percent of non-survivors), 19 percent of all patients had diabetes (31 percent of non-survivors), and 8 percent had cardiovascular disease (13 percent in non-survivors).
Another cohort of 138 hospitalized patients from Wuhan, China2 showed that comorbidities, and cardiovascular disease, in particular, were prevalent. About 45 percent of all patients and 72 percent of patients requiring intensive care unit (ICU) care had comorbidities. In addition, about 31 patients had hypertension (58 percent requiring ICU care), 15 percent had cardiovascular disease (25 percent of patients in ICU care) and 10 percent had diabetes (22 percent of those requiring ICU care). Concerning heart disease, 16.7 percent of patients developed arrhythmia and 7.2 percent experienced acute cardiac injury.
Furthermore, an outpatient and inpatient cohort of 1,099 COVID-19 patients in mainland China3 showed that 24 percent of patients and 58 percent of patients with intubation or death had comorbidities. Hypertension was found in 15 percent (36 percent among those with intubation or death), diabetes in 7.4 percent (27 percent among those with intubation or death), and coronary heart disease in 2.5 percent (9 percent among those with intubation or death).
Regarding these findings, Kim said "about 80 percent of COVID-19 patients experience mild disease or asymptomatic disease while about 15 percent experience severe illness, and the remaining 5 percent face critical illness. Of the critically ill patients, about half die. The risk factors for mortality are known as old age, comorbidities such as cardiovascular disease, lymphopenia, and higher LDH."
SARS-Cov-2 Entry into Cells via ACE2 Increases Heart Patients' Vulnerability
A study published in Circulation that analyzed the relationship between cardiovascular disease and COVID-19 stated that "[although] the mechanism of these associations remains unclear, potential explanations include cardiovascular disease being more prevalent in patients with advancing age, a functionally impaired immune system, or elevated levels of ACE2, or patients with CVD having a predisposition to COVID-19."
The coronaviruses (CoVs) are a large group of single-strand RNA viruses that infect a broad range of species. These viruses are extensive in bats but can also be spread to other birds and mammals, including humans.
In humans, CoVs can cause anything from the common cold (229E, OC43, NL63, and HKU1) to fatal respiratory illnesses that spread in human-to-human transmissions such as the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The most recent, and 7th known human coronavirus, SARS-CoV-2 (known as COVID-19), broke out in China in late December last year and has spread to more than 185 countries, causing millions of deaths.
SARS-CoV-2 first attaches to human cells via the ACE2 receptor, and releases its RNA into the cell and creates virus replicates for its survival. Then, it leaves the host cell to enter other host cells. During this process, many host cells die from their direct cytopathic effect. The body's immune response, in which the host fights against the virus, also damages many infected cells as well as surrounding tissues which can in some instances lead to death.
"Because ACE2 expression in the heart is highest in pericytes, SARS-CoV-2 may invade the pericytes and cause capillary endothelial cell dysfunction," Kim said. "The abundant expression of ACE2 by endothelial cells also can reduce its ability to prevent thrombosis upon entry of SARS-CoV-2 into cells."
"Some excess cytokines during viral infection can also mediate myocardial injury. Underlying cardiovascular disease, as well as aging, also increased ACE2 receptor expression," Kim added. "So, it is possible that patients with cardiovascular disease might have more susceptible host cells for SARS-CoV-2 entry than patients without cardiovascular disease."
Guidelines Recommend Screening, PPE, Treatment Although "No One Size Fits All"
Studies on the relationship between underlying cardiovascular disease and mortality risk of COVID-19 has prompted medical societies to recommend guidelines on how to treat this particular subset of patients.
Many guidelines focus on first screening for COVID-19, addressing safety concerns of both the patient and the medical team, and executing a treatment strategy that is unique to the pandemic.
According to Society for Cardiovascular Angiography and Interventions (SCAI) president Ehtisham Mahmud, the problem that the pandemic brings to cardiology is two-fold. First, cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating an ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury.
The second is that the prevalence of the COVID-19 disease in the U.S. remains unknown and there is the risk of asymptomatic spread.
It is for these reasons that the ACC/SCAI recently recommended that elective cardiac procedures, particularly in patients with comorbidities, be pushed back during the COVID-19 outbreak considering the risks of infection in the hospital setting and patient safety.
In a more comprehensive light, the European Society of Cardiology (ESC)4 recognized that "not one size fits all" since countries have varying levels of transmission.
The ESC pointed out that in one study, about 41 percent of all infections were acquired infection in the hospital and more than 70 percent of these patients were health care professionals. Because the virus poses risk to health care professionals, the ESC guidance recommends protection against COVID-19 according to the level of risk based on patient presentation, types of procedures and interactions, as well as the risk status of health care professionals.
In a cath lab where there are high rates of community infection, the ESC guidance heavily recommends wearing personal protective equipment as well as health care professionals donning surgical masks under the assumption that all patients are potentially infected.
For patients with myocardial infarction with ST-segment elevation, the guidance notes that it might not be possible to wait for a nasopharyngeal swab result and recommends performing the procedure in a dedicated COVID-19 cath lab when available.
For myocardial infarction with non-ST-segment elevation, high-risk patients should be treated under STEMI protocol and others should undergo a swab immediately after admission. If the test turns up positive, and an invasive approach is clinically indicated, the procedure should be performed in a dedicated COVID-19 cath lab.
Balancing Act Between Feasibility and Safety
As an expert in infectious diseases, Kim drew upon his experience on the ground, saying that "if the area has a high prevalence of COVID-19, screening for COVID-19 may be effective since many patients have asymptomatic infection."
"However, in areas with a low prevalence of COVID-19, the screening test performed on patients with coronary disease may not be cost-effective," Kim said. "If physicians are not sure of the status of COVID-19 in heart patients, wearing personal protective equipment including masks, goggles, gloves, and gowns is recommended."
"Shortage of ICU beds was common during the on-going COVID-19 outbreak," he added.
In this regard, delaying elective surgery and procedures that require ICU admission is recommended but this recommendation should be balanced between available ICU beds and the harmful effect of the delaying procedures on the patients in given areas.
Hope for Vaccine, and Utilizing Everything in Between
To treat COVID-19, researchers around the globe have been interlocked in a race to find a cure. In this process, there has been much controversy over antiviral therapies, steroids, ACE inhibitors/ARBs, and drugs such as hydroxychloroquine.
ACE inhibitors have been mired in scientific controversy over theoretical concerns that they improve conditions or cause harm. However, reassuring evidence is currently pointing towards antihypertensive drugs as safe.
"The use of ARB or ACE inhibitors in patients with underlying heart diseases theoretically have beneficial or detrimental effects on COVID-19. Recent observational studies however have revealed that there is no harmful or beneficial effect of these antihypertensive agents on the development of COVID-19 or clinical outcome of COVID-19," Kim said.
Although recent entries such as the steroid dexamethasone and the antiviral remdesivir are being tested in clinical trials - with positive results heralded in the media - Kim notes that there is yet to be a cure for the virus, recommending that until a vaccine is developed and distributed, non-pharmaceutical interventions are critical.
"Currently, remdesivir is the only antiviral agent for severe COVID-19 patients that was demonstrated by a placebo-controlled randomized trial. There are no proven antiviral agents for mild COVID-19," Kim said.
"Key factors to control the epidemic are antiviral agents to treat COVID-19 patients and vaccines to increase herd immunity but developing these require time," he added. "Until these are available, non-pharmaceutical interventions including social distancing and masks along hand hygiene are the most important measures for widespread prevention."
- Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-1062. doi: 10.1016/S0140-6736(20)30566-3
- Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061-1069. doi: 10.1001/jama.2020.1585