European Journal of Cardiovascular Medicine

The global community is currently facing an unprecedented pandemic caused by a newly discovered coronavirus called SARS-CoV-2, which results in the illness known as COVID-19. Following the initial reports of unusual pneumonia cases originating from Wuhan province in China in December 2019, the virus rapidly spread globally, impacting millions of individuals within a few weeks.[1]SARS-CoV-2 belongs to the Corona- viridae family and shares significant similarities with the two other coronaviruses, SARS and MERS.[2] COVID-19 primarily impacts the respiratory system, causing pneumonia and acute respiratory distress syndrome (ARDS) as the main manifestations. Recent reports have emphasised

the influence of SARS-CoV-2 on the cardiovascular system.[3-5]

Individuals who have risk factors for cardiovascular disease (CVD), such as hypertension, diabetes, and dyslipidemia, have a higher likelihood of developing infections and experiencing negative outcomes.[6] There is a growing number of reports on cardiovascular complications, including acute myocardial injury, heart failure (HF), cardiac arrhythmias, myocarditis, pericarditis, and venous thromboembolism.[2,5] Furthermore, the concurrent administration of multiple drugs that prolong the QT-interval, such as hydroxychloroquine (HCQ) and azithromycin, for the treatment of COVID-19 infection can potentially result in a higher occurrence of life-threatening abnormal heart rhythms known as malignant arrhythmias, specifically torsades de pointes (TdP).[2] There is a scarcity of information concerning cardiovascular complications, particularly in developing nations. The objective of this study is to ascertain the cardiovascular complications in symptomatic COVID-19 patients and evaluate how these complications affect the outcomes of the disease.

We conducted a retrospective, observational study among 100 COVID-19 patients (who were confirmed by reverse transcription–polymerase chain reaction) between June 2021 and December 2021. The data were collected from COVID care centers and hospitals. Patients were randomly separated into two groups: Group A (25) to formulate the risk scoring and Group B (75) to see various risk factors . The exclusion criteria were as follows: 

Among patients in Group A, those who experienced cardiovascular (CV) events differed significantly from those without such events across various clinical variables. The group with CV events (n=25) had a notably higher mean age (64.53 years) compared to those without events (53.1 years), with a significant difference (p < 0.001). Additionally, a larger proportion of patients aged 60 and above experienced CV events (16 out of 25) compared to those without events (27 out of 75), indicating age as a significant risk factor (p < 0.001). Male sex was also more prevalent among patients with CV events, with 17 males in this group compared to 33 males in the non-event group (p < 0.001).

Vital signs on admission, including systolic and diastolic pressure, respiratory rate, heart rate, and temperature, did not show significant differences between the two groups. However, some symptoms and signs were more frequently reported among patients with CV events, including cough (p = 0.002), fever (p = 0.031), and shortness of breath/dyspnea (p = 0.076).

Regarding comorbidities, diabetes mellitus was more prevalent among patients with CV events (p = 0.036), while chronic liver disease showed no significant difference. However, hypertension (p = 0.096) and coronary heart disease (CHD) (p < 0.001) were more prevalent in the CV event group.

In summary, older age, male sex, cough, fever, dyspnea, and diabetes mellitus were associated with a higher likelihood of experiencing CV events among patients in Group A. Additionally, the presence of hypertension and CHD increased the risk of such events.

eGFR:Estimated glomerular filtration rate, APTT: Activated partial thromboplastin time, CRP:C-reactiveproteins, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, CHD: Chronic heart disease

Multivariate analysis conducted on risk factors for cardiovascular complications in Group A revealed several significant predictors. Male sex, older age (≥60 years), presence of cough, coronary heart disease (CHD), lymphocyte count (≤1.10 × 10^9/L), blood urea nitrogen levels (≥7.0 mmol/L), estimated glomerular filtration rate (eGFR) (≤90.0 ml/min/1.73 m^2), activated partial thromboplastin time (APTT) (≥37 seconds), elevated D-dimer levels (≥0.50 mg/L), and procalcitonin levels (≥0.5 μg/L) exhibited significant odds ratios (ORs) with p-values < 0.05. These findings underscore the multifactorial nature of cardiovascular complications in this patient cohort, with factors ranging from demographic characteristics to various hematological and biochemical parameters contributing to the risk assessment. The assigned scores indicate the relative weight of each factor in predicting the likelihood of cardiovascular events, with higher scores corresponding to greater significance.

OR: Odds ratio, CI: Confidence interval, eGFR: Estimated glomerular filtration rate, APTT: Activated partial thrombo- plastin time, CHD: Chronic heart disease.

There have been ten recognized risk factors. We noted a progressive growth in the overall score, which rose from 0 to 23 points. The new grading method is directly correlated with the prognosis of COVID-19 patients in respect to cardiovascular problems. Therefore, it is crucial and essential to make an early prediction of cardiovascular problems. Our investigation shares similarities with the study conducted by Wei et al.[7], in which they found associations between procalcitonin, prior cardiovascular disease, age, illness, and estimated glomerular filtration rate (eGFR) and acute myocardial infarction (AMI). A risk score is widely acknowledged to be more effective than a single indication in COVID-19 for comprehensive categorization. We have developed a new scoring system that takes into account demographic factors, symptoms, comorbidities, and laboratory tests. The study participants were divided into two groups. Previous examinations have demonstrated that approximately 10% of patients with COVID-19 experienced myocardial damage. The interval [8,9] Our investigation found that approximately 16% of the individuals experienced complicated cardiovascular events. The occurrence of cardiovascular events may vary depending on various circumstances, including the demographics of the community and the severity of the disease. It has been well confirmed that being male, having a prolonged activated partial thromboplastin time (APTT), being older, having coronary heart disease (CHD), and having elevated levels of D-dimer are all related with cardiovascular events in the risk score. Pneumonia (community acquired) is similarly associated with similar risk factors.[10] In our investigation, a limited number of independent concerns have been newly found, which should be handled with caution. In Irwin's evaluation, he mentioned that the cough could potentially result in cardiovascular issues.[11]Nevertheless, the impact of cough on patients has to be elucidated. COVID-19 patients often exhibit decreased lymphocyte counts, which can be attributed to systemic inflammatory responses and immunocompromisation.[8,9] Several investigations have shown that severe cases of COVID-19 exhibit reduced amounts of T suppressor and helper cells.[12]. The influence of COVID-19 on lymphocytes can result in a range of cardiovascular problems.[13] The association between cardiovascular events and blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) in COVID-19 is uncertain. Regardless, our results are consistent with a previous study on influenza. In the investigation conducted by Nin et al., it was discovered that the H1N1 virus In patients with acute renal injury, there is a greater presence of cardiovascular dysfunction compared to those without when they have pneumonia.[14] Procalcitonin demonstrates exceptional accuracy in the clinical setting for the evaluation of bacterial infections. Bacterial infections are frequently observed in individuals with cardiovascular complications due to their compromised immune system. There is a limited number of studies that establish the correlation between procalcitonin and cardiovascular morbidity and mortality.[15] Historically, risk factor models similar to our design have been employed in predicting ICU admissions, severe illness, and mortality among COVID-19 patients. Gong et al. conducted a study in which they created a "nomogram" that demonstrated a correlation between elevated BUN levels and advanced age with severe cases of COVID-19.[16] Our risk scores have shown a decrease in the area under the curve compared to the previous predictive models, with a range of 0.80-0.90. As a result of the retroactive design plan, certain fundamental data were not recorded, which could have compromised the effectiveness of the risk score's ability to differentiate between different levels of risk. At that juncture, it is possible that the termination point of cardiovascular events exhibited greater diversity than the disease itself. Moreover, the illness severity of various cardiovascular events in the included individuals was not comparable. In order to ensure impartiality throughout the trial, the researchers utilized the approved definitions to diagnose the disease in the patients, and multiple doctors were assigned to verify the data. Based on our research, the specific risk variables can be readily acquired and assessed. It can aid doctors in determining optimal treatment options for patients who are at risk of cardiovascular complications, and support future scientific investigations into the mechanism of cardiovascular events in COVID-19.Our investigation has certain limitations. Initially, it was a thorough examination that may have been influenced by the selective inclusion of data. The drugs and therapies administered before admission may have influenced the outcomes. There was a lack of extended monitoring. An investigation will be conducted to examine the long-term effects of SARS-CoV-2 on cardiovascular systems and the associated risk factors. We need to do study on a larger population to confirm our hypotheses.

Ten risk factors were evaluated upon admission: male gender and advanced age, coronary heart disease, reduced kidney function (eGFR ≤90 ml/min/1.73 m2), elevated D-dimer levels (≥0.5 mg/L), low lymphocyte count (≤1.1 × 109/L), presence of cough and fever, elevated procalcitonin levels (≥0.5 μg/L), high blood urea nitrogen levels (≥7 mmol/L), and prolonged activated partial thromboplastin time (APTT) (≥37 seconds). These factors provide a basis for estimating the likelihood of cardiovascular complications in COVID-19 patients, though further research is needed to validate their predictive value.

1. Zhu N, Zhang D, Wang W, et al. China novel coronavirus investigating andresearch team. A novel coronavirus from patients with pneumonia in China,NEngl JMed. 2020;382:727e733.
2. KunalS, GuptaK, Sharma SM,etal. Cardiovascular system and COVID19: perspectives from a developing country. Monaldi Arch Chest Dis.2020;90. https://doi.org/10.4081/monaldi.2020.1305.
3. ShiS,QinM, ShenB,etal. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5 (7): https://doi.org/10.1001/ jamacardio.2020.0950.
4. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes ofpatients with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5 (7): https://doi.org/10.1001/ jamacardio.2020.1017.
5. DengQ,HuB,Zhang Y,etal. Suspected myocardial injury in patients with COVID-19: evidence from front-line clinical observation in Wuhan, China. Int JCardiol.2020; 311:116e121. https://doi.org/10.1016/j.ijcard.2020.03.087.
6. Guan WJ, Liang WH, Zhao Y, et al. China Medical Treatment Expert Group forCOVID-19.Comorbidity and its impact on1590 patients with COVID-19  in China: anation wide analysis. EurRespirJ.2020;55:2000547.
7. Wei JF, HuangFY, XiongTY, Liu Q, Chen H, WangH, etal. Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis. 2020;106:1154–9. [PMCID: PMC7398466] [PubMed: 32354798]
8. HuangC, WangY, Li X, Ren L, Zhao J, Hu Y, etal. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 2020;395:497–506. [PMCID: PMC7159299] [PubMed: 31986264]
9. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323:1061–9. [PMCID: PMC7042881] [PubMed: 32031570]
10. Violi F, Cangemi R, Falcone M, Taliani G, Pieralli F, Vannucchi V, et al. Cardiovascular complications and short-term mortality risk in community – Acquired pneumonia. Clin Infect Dis. 2017;64:1486–93. [PubMed: 28205683]