SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Cardiovascular Outcomes in Non-Cancer Patients with COVID-19
3. Outcomes in Cancer Patients
4. Fatal Myocarditis
5. Venous Thromboembolism
6. Coagulation Dysfunctions: What about the Impact of Anticancer Therapies and Type of Cancer?
7. Angiotensin-Converting Enzyme 2 and Serine Protease TMPRSS2: Role in COVID-19 and Involvement in Cardio-Metabolic Risk Factors
8. Cardiovascular Microenvironment: A Focus on Cytokine Storm
9. Non-Pharmacological Strategies to Reduce Cardiovascular Events in Cancer Patients with COVID-19
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- Reduce total body fat, especially visceral fat; pay attention to body weight;
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- Do daily exercise, at any time of the day; reduce the time spent on television;
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- Limit consumption of energy-dense foods and avoid sugary drinks;
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- Eat mostly foods of plant origin and follow a diet rich in whole grains, vegetables (non-starchy), fruit, and legumes;
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- Limit the consumption of red meats (beef, pork, sheep), cured meats, and preserved meats;
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- Limit alcohol consumption;
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- For cancer prevention, do not use supplements. Try to meet nutritional needs through diet alone;
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- For mothers: if you have the opportunity to breastfeed, this has benefits for the baby and the mother.
10. Conclusions
Funding
Conflicts of Interest
References
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Study | Date of Publication | Total Patients (n) | Type of Population | Outcomes in Cancer Patients | Reference |
---|---|---|---|---|---|
Liang et al. | 14 February 2020 | 1580 | Chinese | 1% (95% CI 0.61–1.65) of COVID-19 cases had a history of cancer. Cancer patients have a high probability of severe events than non-cancer patients (hazard ratio 3.56, 95% CI 1.65–7.69). Risk of clinically severe events in cancer patients who underwent chemotherapy or surgery in the past month is higher than other cancer patients (odds ratio 5.34, 95% CI 1.80–16.18; p = 0.0026). | [21] |
Jing Yu et al. | 25 March 2020 | 1524 | Chinese | Patients with cancer had a higher risk of SARS-CoV-2 infection (OR, 2.31; 95% CI, 1.89–3.02) compared with other people. | [22] |
Guan et al. | 26 March 2020 | 1590 | Chinese | Cancer patients had a hazard ratio of 3.50 (95% CI, 1.60–7.64) for admission to intensive care unit, or invasive ventilation, or death, compared to non-cancer patients. | [23] |
Istituto Superiore di Sanità | 2 April 2020 | 909 | Italian | Among 909 patients who died, more than 50% had three or more comorbidities such as ischemic heart disease (27.4%), atrial fibrillation (23%), heart failure (16.4%), stroke (12%), hypertension (73.5%), diabetes mellitus (31.5%), and active cancer in the past 5 years (16.5%) | [24] |
Trapani et al. | 28 April 2020 | 9 | Italian | All cancer patients with COVID-19 had a smoking history, being either former smokers (n = 4) or current smokers (n = 5). Comorbidities were arterial hypertension (n = 4), diabetes mellitus type II (n = 2), and chronic kidney diseases. | [25] |
Montopoli et al. | 29 April 2020 | 9280 | Italian | Cancer patients have an increased risk of SARS-CoV-2 infections than non-cancer patients. 8.5% had a diagnosis of cancer and 1.3% had prostate cancer. Comparing the total number of SARS-CoV-2 positive cases, patients with prostate cancer receiving androgen-deprivation therapy had a significantly lower risk of SARS-CoV-2 infections compared to patients who did not receive androgen-deprivation therapy (OR 4.05; 95% CI 1.55–10.59). | [26] |
de Rojas et al. | 8 May 2020 | 15 | Spanish | The prevalence of COVID-19 infection among children with cancer in Madrid is 1.3% vs. 0.8% of the general pediatric population. | [28] |
Wu et al. | 24 February 2020 | 72314 | Chinese | Case fatality report was higher among patients with pre-existing comorbidities: 10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer. | [29] |
Onder et al. | 23 March 2020 | 1625 | Italian | In a subsample of 355 COVID-19 patients who died in Italy, 30% had ischemic heart disease, 35.5% had diabetes, 20.3% had active cancer, 24.5% had atrial fibrillation, 6.8% had dementia, and 9.6% had a history of stroke. | [30] |
Zhang et al. | 26 March 2020 | 28 | Chinese | The mortality rate of cancer patients was 28.6% (more than ten times higher than that reported in all COVID-19 patients in China). The recent use of anticancer therapies within 14 days of infection (including chemotherapy, immunotherapy, and radiation) was an independent predictor of death or other severe events with a hazard ratio > 4. | [31] |
Bonomi et al. | 31 March 2020 | Single report | Italian | A 65-year-old patient with metastatic non-small-cell lung cancer in treatment from 6 years with anti PD-1 antibody (nivolumab). After COVID-19 diagnosis and hospitalization, the patient presented a rapid evolution of respiratory failure and was not treated with more invasive procedures, probably due to his cancer and emphysema history. The authors discuss the need for a multidisciplinary approach for the management of COVID-19-infected cancer patients. | [32] |
He et al. | 1 April 2020 | 128 | Chinese | There was no significant difference in the proportion of patients with hematological cancers vs. healthy subjects (10% vs. 7%, p = 0.322), but a significant difference was seen in fatality rate (62% vs. 0%, p = 0.002). Among cancer patients, 39% had acute myeloid leukemia, 20% had acute lymphoblastic leukemia, 59% had received chemotherapy in the last 7–19 days. | [33] |
Miyashita et al. | 21 April 2020 | 334 | American | Patients with cancer were significantly more likely to require intubation (RR 1.89, 95% CI 1.37–2.61) than non-cancer patients. Cancer patients younger than 50 years of age had a significantly higher rate of mortality than the other (RR 5.01, 95% CI 1.55–16.2). | [34] |
Dai et al. | 28 April 2020 | 641 | Chinese | Patients with cancer had a higher mortality rate than those without (odds ratio 2.34, 95% CI 1.15–4.77, p = 0.03. The death rate was highest in those with hematological cancer (33.33%) and lung cancer (18.18%). Patients with metastatic cancer had a higher risk of death (OR 5.58, 95% CI 1.71–18.23, p = 0.01). Patients with cancer were significantly more likely to require ICU admission (OR 2.84, 95% CI 1.59–5.08, p < 0.01) and have higher rates of severe/critical symptoms (OR 2.79, 95% CI 1.74–4.41, p < 0.01). | [35] |
Deng et al. | 28 April 2020 | 44672 | Chinese | Patients with cancer had a significantly higher risk of death than those without (RR 2.93, 95% CI 1.34–6.41, p = 0.006) | [36] |
Mehta et al. | 1 May 2020 | 218 | American | The mortality rate in cancer patients with COVID-19 was 25% for solid tumors and 37% for hematological malignancies. | [37] |
Cytokine | Involvement in Pathogenesis of COVID-19 and Cardiovascular Diseases | References |
---|---|---|
Interleukin-1β (IL-1β) | Interleukin-1β is significantly increased in COVID-19 patients vs. healthy subjects, and it is one of the most important and studied cardiovascular risk factor involved in the NLRP3 inflammasome activation; it has been studied for many years in cardio-oncology; in fact, its expression is enhanced during doxorubicin-induced cardiotoxicity. Some IL-1-blocking antibodies are currently under study and used in clinical trials with great improvements of cardiovascular outcomes. Moreover, IL-1 promotes the expression of other pro-inflammatory cytokines, including interleukin-6 and cardiovascular risk factors such as hs-CRP. | [105,106,107,108,109] |
Interleukin-2 (IL-2) | Interleukin-2, overexpressed in both ICU-COVID-19 and non-ICU COVID-19 patients, indicating a Th1 immune reaction to SARS-CoV-2, is a T-cell growth factor of key importance in immune-reactive processes. High levels of IL-2 receptor are associated to rheumatoid arthritis multiple sclerosis and coronary artery diseases; two case reports described myocarditis induced by an overexpression of myocardial IL-2. | [110,111,112,113] |
Interleukin-7 (IL-7) | Interleukin-7 (IL-7) is a key regulator of T-cell growth; IL-7 recruits monocytes and macrophages to the endothelium and plays a crucial role in the pathogenesis of atherosclerosis through PI3K-AKT and NF-kB pathways; in another study, IL-7 promoted clinical instability in patients with coronary artery disease. | [114,115] |
Interleukin 6 (IL-6) | Interleukin 6, which is significantly increased in COVID-19 patients compared to healthy subjects (but without differences compared to ICU-patients), is another key regulator of immune-related reaction. IL-6 is studied in oncology and cardio-oncology because it is a key promoter of cancer survival, chemoresistance, anticancer-induced cardiotoxicity, and cancer progression. Meta-analysis confirmed the association between IL-6 receptor and coronary heart diseases, and in a recent study in 2329 patients with heart failure, high plasma levels of IL-6 (seen in 50% of patients) were associated to atrial fibrillation, a reduction of Left Ventricular Ejection Fraction (LVEF), and a worse prognosis. | [116,117,118] |
Interleukin-12 (IL-12) | Interleukin-12 acts as a protective cytokine in anticancer-induced myocardial injuries, although some authors discussed on its possible association to heart failure or atherosclerosis; however, the role of IL-12 remains controversial and needs further observational and interventional studies. | [119] |
Granulocyte-colony-stimulating-factor (G-CSF) | Granulocyte colony-stimulating-factor (G-CSF) is produced by leukocytes and fibroblasts; it is well associated to a higher risk of MACE (death, myocardial infarction, re-hospitalization) in patients with stable coronary artery disease, although other authors discussed its cardioprotective role through the induction of tissue repair after myocardial infarction. | [120,121] |
C-X-C motif chemokine 10 (CXCL10 or Induced protein 10) | C-X-C motif chemokine 10 (CXCL10 or induced protein 10) is a chemoattractant chemokine of Th1 and cytotoxic T cells. It is overexpressed in viral myocarditis, coronary atherosclerosis, hypertension, and left ventricular dysfunction. | [122,123,124,125] |
CCL2 (Monocyte Chemoattractant Protein (MCP-1) | CCL2 (Monocyte Chemoattractant Protein, called also MCP-1) in another well-known cytokine in cardiology, strictly related to several cardiovascular events such as atherosclerosis, myocardial injury, hypertension, angiotensin-2 homeostasis (through functional interaction with angiotensin2 type 1 receptor), and other diseases. | [126] |
Tumour Necrosis Factor-α (TNF-α) | TNF-α, significantly associated to severe cases of COVID-19, has been studied as a driver of vascular dysfunction, atherosclerosis, and heart failure. | [127] |
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Quagliariello, V.; Bonelli, A.; Caronna, A.; Conforti, G.; Iovine, M.; Carbone, A.; Berretta, M.; Botti, G.; Maurea, N. SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients. Cancers 2020, 12, 3316. https://doi.org/10.3390/cancers12113316
Quagliariello V, Bonelli A, Caronna A, Conforti G, Iovine M, Carbone A, Berretta M, Botti G, Maurea N. SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients. Cancers. 2020; 12(11):3316. https://doi.org/10.3390/cancers12113316
Chicago/Turabian StyleQuagliariello, Vincenzo, Annamaria Bonelli, Antonietta Caronna, Gabriele Conforti, Martina Iovine, Andreina Carbone, Massimiliano Berretta, Gerardo Botti, and Nicola Maurea. 2020. "SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients" Cancers 12, no. 11: 3316. https://doi.org/10.3390/cancers12113316