Heart discomfort is a common symptom of patients with COVID-19, mainly including chest pain, palpitations, fatigue, shortness of breath, etc. Previous studies have shown that the new coronavirus will cause damage to the cardiovascular system, may impact the heart, and even cause serious complications such as myocarditis and myocardial infarction. The mechanism is mainly related to myocardial injury. The first cause is that the virus directly invades the cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of myocardial cells, the second is a myocardial injury caused by an immune inflammatory response and cytokine storm, and the third is an ischemic myocardial injury caused by cellular hypoxia. A cohort study involving 12,095,836 cases found that even people without high-risk factors for cardiovascular disease still had an increased risk of cardiovascular disease after infection with the new coronavirus. Paying attention to the impact of the new coronavirus on the heart and studying the risk factors of related sequelae are crucial to predicting the occurrence of sequelae and improving the quality of life of patients.
Existing studies have shown that aging is an independent risk factor for COVID-19. Electronic health record (EHR) analysis of age and long-term diagnosis of new coronavirus shows that the long-term risk of COVID-19 virus is associated with age in an inverted U shape. The risk of 45 to 54 years old and 55 to 69 years old are the highest; the risk was not higher among those aged 80 years and older than the reference population aged 18 to 24.1 This study found that young people have a higher risk of cardiovascular sequelae than middle-aged and elderly after being infected with the COVID-19. In addition, high work pressure, eating disorders, and bad living habits of young people may also be influencing factors. Studies have observed that vaccination with the second dose of mRNA-1273 vaccine may increase the probability of myocarditis in young people, so the higher risk of cardiovascular sequelae in young people may be related to vaccination.2 In addition, Osmanov et al. believe that in children and adolescents, immune mechanisms may be responsible for the increased risk of long-term consequences of infection, and the sequelae of COVID-19 may be associated with the immune responses of mast cell activation syndrome and helper T cell type 2 (Th2) in children with allergic diseases.3
This study shows that female is an independent risk factor for cardiovascular sequelae, especially persistent fatigue, post-exercise dyspnea, and smell and taste disturbance. Studies have shown that there seem to be significant gender differences in long-term cardiovascular outcomes after COVID-19. Middle-aged women are twice as likely to suffer from long-term COVID-19 as men. The difference in inflammatory load between male and female populations may explain the gender differences in clinical manifestations and cardiovascular outcomes after COVID-19.4 Previous studies have also shown that women are associated with COVID-19 symptoms, especially persistent fatigue, anxiety, and depression. The reason may be that women have a stronger immune response. For example, women have a higher proportion of autoimmune diseases. It has been reported that women produce stronger immunoglobulin G (IgG) antibodies in the early stage of the disease, which may lead to more favorable outcomes in women. Women recover more quickly from COVID-19 but may also play a role in perpetuating disease manifestations.5 Even after recovery, estrogen in women may maintain the role played in the hyper-inflammatory state of the acute phase, which may also increase the risk of developing COVID-19.6,7 In addition, women are generally more concerned about their bodies and related pain, which may also be the reason why the survey shows that women are at higher risk of developing COVID-19.8
Patients with previous cardiovascular diseases are more likely to be infected with the new coronavirus. The virus has long-term potential effects on heart damage and is more likely to have related symptoms such as palpitations or chest pain. Patients with existing cardiometabolic diseases may have a higher risk of developing an acute state after infection with the new coronavirus, accompanied by complications and significantly affecting the prognosis.9 On the other hand, COVID-19 itself may aggravate cardiac damage. It has been reported that previous history of coronary heart disease and elevated cardiac troponin I (cTnI) levels are two independent determinants of clinical status in COVID-19 patients.10 Elderly patients with coronary heart disease, hypertension, diabetes, and chronic kidney disease are more likely to develop severe sequelae after COVID-19. Transthoracic echocardiogram (TTE) imaging showed regional wall motion abnormalities, left or right ventricle abnormalities, systolic dysfunction, diastolic dysfunction, and pericardial effusion in the acute phase of COVID-19.11 In patients diagnosed with various heart diseases, COVID-19 infection may be one of the triggers for exacerbation and death;12 patients with new-onset myocardial dysfunction, inflammation or cardiovascular magnetic resonance (CMR) scarring after COVID-19 may have increased risk of cardiac failure or recurrence of arrhythmia.13 Patients with hyperglycemia have metabolic abnormalities, and patients with metabolic abnormalities have a higher risk of severe COVID-19 and COVID-19 sequelae. Obesity is a risk factor for cardiovascular disease, and the possible mechanisms include sympathetic nerve activation, endothelial dysfunction, oxidative stress, rheumatoid arthritis (RA) activation, metabolic dysfunction, etc., which can affect hemodynamics and cardiac structure, thereby increasing palpitations and the risk of developing related symptoms.
Alcohol consumption is a well-recognized risk factor for cardiovascular disease. Statistical analysis of the data in this study found that a history of alcohol consumption reduced the risk of increased chest pain severity. However, the small sample size may lead to statistical bias in the data, hence, no conclusion can be drawn. Additionally, the study demonstrated a J-shaped relationship between alcohol consumption and cardiovascular disease incidence, total mortality, and cardiovascular disease mortality in multivariate models. In a multivariable model, alcohol intake of 5 to 14.9g per day was associated with a 26%, 35%, and 51% lower risk of cardiovascular disease, total mortality, and cardiovascular disease mortality, respectively, compared with abstainers. The mechanism may be related to the effect of alcohol on lipids and insulin sensitivity;14 there is also evidence that alcohol consumption is positively associated with coronary artery disease, atrial fibrillation, and abdominal aortic aneurysm, but this association is attenuated after adjustment for smoking, hence smoking may have some effect in that study;15 alcohol abuse is associated with increased odds of clinically high serum total cholesterol and triglyceride levels,16 but a short-term intervention study showed that moderate alcohol consumption reduced several cardiovascular biomarkers including high-density lipoprotein, adiponectin levels, and fibrinogen.17 Although some studies in the past have shown that light drinking may have a protective effect on ischemic heart disease in women, the irreversible damage caused by alcohol to the cardiovascular system has offset this protective effect. The relationship between drinking history and drinking volume with COVID-19 still needs further research.
4.1 Limitations of the study
There are a few limitations in this study. First, this study only involved patients from a single center. The sample size was small, so there was a statistical bias. Second, most symptoms are subjective and easily affected by subjective bias. Third, this study lacks the assessment of the patients’ symptoms before and during the infection of COVID-19. A comparative analysis of the patients’ symptoms before and after the COVID-19 infection will be of great significance in evaluating the impact of the COVID-19 sequelae on various systems. Lastly, although this study has made statistics on the sequelae of COVID-19, it lacked quantitative and specific indicators. For example, "fatigue" is one of the main sequelae. If relevant scales are applied for objective and comparative analysis, the results can be more persuasive.