Impact of age dominating over the pre-existing comorbidities influencing the D-Dimer levels in SARS-COV-2 infection
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Abstract
COVID-19-related disease severity is more commonly seen in elderly patients with comorbidities, and hypercoagulability has been demonstrated to be involved in the disease progression. This study aimed to evaluate the level of D-Dimer in hospitalized SARS-COV-2 infected patients and to determine the influence of age, gender, Body Mass Index (BMI), and comorbidities on D-dimer value and correlate it with disease severity. This case-control retrospective study retrieved patient data on demographic characteristics, vital functions, comorbidities, disease severity [National Institutes of Health (NIH) classification], and D-dimer from medical records of Thumbay University Hospital, Ajman, United Arab Emirates. SPSS-Version-28 was used for data analysis; a Chi-Square test was done to compare the distribution of comorbidities and disease severity between demographic categories. An independent sample t-test and one-way ANOVA were done to compare mean levels of D-Dimer between two or more categories, respectively. The majority of patients were males, ˃40 years of age, overweight/obese, with 30% having one comorbidity and 20% having ≥2 comorbidities. Among the total, three-quarters had moderate, and one-quarter had severe disease conditions, irrespective of gender or BMI, with an increasing trend of severe cases in the older age group and with comorbidities. Increased D-dimer levels were seen in the majority of SARS-COV-2-infected hospitalized patients, with age as the primary determinant, irrespective of absence or presence of comorbidity, though the trend of higher prevalence of elevated D-dimer value in the multiple comorbid groups and more severe condition was observed. Supporting SAR-COV-2 as a coagulopathic condition, D-dimer concentrations can be a helpful marker of disease progression and can be considered to guide the clinical treatment.
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Keywords
Coagulopathy, Comorbidity, COVID-19, D-dimer, SAR-COV-2 infection
References
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Bikdeli, B., Madhavan, M. V., Jimenez, D., Chuich, T., Dreyfus, I., Driggin, E., Nigoghossian, C. D., Ageno, W., Madjid, M., Guo, Y., Tang, L. V., Hu, Y., Giri, J., Cushman, M., Quéré, I., Dimakakos, E. P., Gibson, C. M., Lippi, G., Favaloro, E. J. & Lip, Y. H. (2020). COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. Journal of the American College of Cardiology, 75(23), 2950-73. doi.org/10.1016/j.jacc.2020.04.03
Bwire, G. M. (2020). Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women?. SN Comprehensive Clinical Medicine, 2(7), 874–876. doi: 10.1007/s42399-020-00341-w.
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X. & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507–513. doi: 10.1016/S0140-6736(20)30211-7.
Griffith, D. M., Sharma, G., Holliday, C. S., Enyia, O. K., Valliere, M., Semlow, A. R., Stewart, E. C. & Blumenthal, R. S. (2020). Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions. Preventing Chronic Disease, 17, E63. doi: 10.5888/pcd17.200247.
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Henkens, M. T. H. M., Raafs, A. G., Verdonschot, J. A. J., Linschoten, M., van Smeden, M., Wang, P., van der Hooft, B. H. M., Tieleman, R., Janssen, M. L. F., Ter Bekke, R. M.A., Hazebroek, M. R., van der Horst, I. C. C., Asselbergs, F. W., Magdelijns, F. J. H. & Heymans, S. R. B. (2022). Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study. BMC Geriatrics, 22(1), 1–11. doi: 10.1186/s12877-021-02673-1.
Kompaniyets, L., Goodman, A. B., Belay, B., Freedman, D. S., Sucosky, M. S., Lange, S. J., Gundlapalli, A. V., Boehmer, T. K. & Blanck, H. M. (2021). Body mass index and risk for COVID-19–related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death—United States. Morbidity and Mortality Weekly Report, 70(10), 355–361.
Li, Y., Zhao, K., Wei, H., Chen, W., Wang, W., Jia, L., Liu, Q., Zhang, J., Shan, T., Peng, Z., Liu, Y. & Yan, X. (2020). Dynamic relationship between D-dimer and COVID-19 severity. British Journal of Haematology, 190(1), 24–27. doi: 10.1111/bjh.16811.
Lim, S., Bae, J. H., Kwon, H. S. & Nauck, M. A. (2021). COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nature Reviews Endocrinology, 17(1), 11–30. doi: 10.1038/s41574-020-00435-4.
Long, H., Nie, L., Xiang, X., Li, H., Zhang, X., Fu, X., Ren, H., Liu, W., Wang, Q. & Wu, Q. (2020). D-Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID-19 and Poor Prognosis. BioMed Research International, 16;2020:6159720. doi: 10.1155/2020/6159720.
Marietta, M., Ageno, W., Artoni, A., De Candia, E., Gresele, P., Marchetti, M., Marcucci, R. & Tripodi A. (2020). COVID-19 and haemostasis: A position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfusion, 18(3), 167–169. doi: 10.2450/2020.0083-20.
McGonagle, D., O’Donnell, J. S., Sharif, K., Emery, P. & Bridgewood, C. (2020). Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. The Lancet Rheumatology, 2(7), 437–445. doi: 10.1016/S2665-9913(20)30121-1.
Miri, C., Charii, H., Bouazzaoui, M. A., Laouan, B. F., Boulouiz, S., Abda, N., Kouismi, H., Bazid, Z., Ismaili, N. & El Ouafi N. (2021). D-dimer Level and Diabetes in the COVID-19 Infection. Clinical and Applied Thrombosis/Hemostasis, 27(1), 1–4. doi: 10.1177/1 07602962 11045902.
Mishra, Y., Kumar, B. & Sourabh, S. (2020). Relation of D-dimer levels of COVID-19 patients with diabetes mellitus. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(6), 1927–1930. doi: 10.1016/j.dsx.2020.09.035.
Moccia, F., Gerbino, A., Lionetti, V., Miragoli, M., Munaron, L.M., Pagliaro, P., Pasqua, T., Penna, C., Rocca, C., Samaja, M. & Angelone, T. (2020). COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches. GeroScience, 42(4), 1021–1049. doi: 10.1007/s11357-020-00198-w.
Mueller, A. L., McNamara, M. S. & Sinclair, D. A. (2020). Why does COVID-19 disproportionately affect older people?. Aging, 12(10), 9959–9981. doi: 10.18632/aging.103344.
National Institutes of Health (2021). Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19). Nih, 2019, 1–243. Available at: https://www.covid19treatmentgu idelines.nih.gov/.%0Ahttps://www.covid19treatmentguidelin s.nih.gov/.
Sahni, S., Gupta, G., Sarda, R., Pandey, S. & Pandey, R. M. (2021). Impact of metabolic and cardiovascular disease on COVID-19 mortality: A systematic review and meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15 (102308) . doi.org/10.1016/j.dsx.2021.
Sharma, A., Garg, A., Rout, A. & Lavie, C. J. (2020). Association of Obesity With More Critical Illness in COVID-19. Mayo Clinic Proceedings, 95(9), 2040–2042. doi: 10.1016/j.mayocp.2020.06.046.
Shibata, S., Arima, H., Asayama, K., Hoshide, S., Ichihara, A., Ishimitsu, T., Kario, K., Kishi, T., Mogi, M., Nishiyama, A., Ohishi, M., Ohkubo, T., Tamura, K., Tanaka, M., Yamamoto, E., Yamamoto, K. & Itoh, H. (2020). Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19. Hypertension Research, 43(10), 1028–1046. doi: 10.1038/s41440-020-0515-0.
Tang, N., Li, D., Wang, X. & Sun, Z. (2020). Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis, 18(4), 844–847. doi: 10.1111/jth.14768.
Thachil, J., Tang, N., Gando, S., Falanga, A., Cattaneo, M., Levi, M., Clark, C. & Iba, T. (2020). ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis, 18(5), 1023–1026. doi: 10.1111/jth.14810.
Van Jaarsveld, G. M. (2020). The Effects of COVID-19 Among the Elderly Population: A Case for Closing the Digital Divide. Frontiers in Psychiatry, 11(1), 1–7. doi: 10.3389/fpsyt.2020.577427.
Xia, F., Zhang, M., Cui, B., An, W., Chen, M., Yang, P., Qin, T., Zhou, X., Liao, Y., Xu, X., Liu, S., Li, K., Zhou, Q., Wang, K., Hu, G., Du, M., Chen, S., Zhang, Y., Wei, W., Xiang, M. & Zhang, J. (2021). COVID-19 patients with hypertension are at potential risk of worsened organ injury. Scientific Reports, 11(1), 1–10. doi: 10.1038/s41598-021-83295-w.
Yang, Q., Zhou, Y., Wang, X., Gao, S., Xiao, Y., Zhang, W., Hu, Y. & Wang Y. (2020). Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis. Respiratory Research, 21(1), 172–181. doi: 10.1186/s12931-020-01435-8.
Zhang, Z., Wan, J., Zhu, S., Wang, M., Wang, X., Tong, X. & Ding, J. (2021). Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity. Medicina Clínica, 159(4), 171-176. doi: 10.1016/j.medcle.2021.09.030.
Zou, Y., Guo, H., Zhang, Y., Zhang, Z., Liu, Y., Wang, J., Lu, H. & Qian, Z. (2020). Analysis of coagulation parameters in patients with COVID-19 in Shanghai, China. BioScience Trends, 14(4), 285–289. doi: 10.5582/bst.2020.03086.
Amin, M. T., Fatema, K., Arefin, S., Hussain, F., Bhowmik, D.R. & Hossain, M. S. (2021). Obesity, a major risk factor for immunity and severe outcomes of COVID-19. Bioscience Reports, 41(8), 1–16. doi: 10.1042/BSR20210979.
Bikdeli, B., Madhavan, M. V., Jimenez, D., Chuich, T., Dreyfus, I., Driggin, E., Nigoghossian, C. D., Ageno, W., Madjid, M., Guo, Y., Tang, L. V., Hu, Y., Giri, J., Cushman, M., Quéré, I., Dimakakos, E. P., Gibson, C. M., Lippi, G., Favaloro, E. J. & Lip, Y. H. (2020). COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. Journal of the American College of Cardiology, 75(23), 2950-73. doi.org/10.1016/j.jacc.2020.04.03
Bwire, G. M. (2020). Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women?. SN Comprehensive Clinical Medicine, 2(7), 874–876. doi: 10.1007/s42399-020-00341-w.
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X. & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507–513. doi: 10.1016/S0140-6736(20)30211-7.
Griffith, D. M., Sharma, G., Holliday, C. S., Enyia, O. K., Valliere, M., Semlow, A. R., Stewart, E. C. & Blumenthal, R. S. (2020). Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions. Preventing Chronic Disease, 17, E63. doi: 10.5888/pcd17.200247.
Hannawi, S., Hannawi, H., Naeem, K. B., Elemam, N. M., Hachim, M. Y., Hachim, I. Y., Darwish, A. S. & Salmi, I. A. (2021). Clinical and Laboratory Profile of Hospitalized Symptomatic COVID-19 Patients: Case Series Study From the First COVID-19 Center in the UAE. Frontiers in Cellular and Infection Microbiology, 11(1), 1–10. doi: 10.3389/fcimb.2021.632965.
Henkens, M. T. H. M., Raafs, A. G., Verdonschot, J. A. J., Linschoten, M., van Smeden, M., Wang, P., van der Hooft, B. H. M., Tieleman, R., Janssen, M. L. F., Ter Bekke, R. M.A., Hazebroek, M. R., van der Horst, I. C. C., Asselbergs, F. W., Magdelijns, F. J. H. & Heymans, S. R. B. (2022). Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study. BMC Geriatrics, 22(1), 1–11. doi: 10.1186/s12877-021-02673-1.
Kompaniyets, L., Goodman, A. B., Belay, B., Freedman, D. S., Sucosky, M. S., Lange, S. J., Gundlapalli, A. V., Boehmer, T. K. & Blanck, H. M. (2021). Body mass index and risk for COVID-19–related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death—United States. Morbidity and Mortality Weekly Report, 70(10), 355–361.
Li, Y., Zhao, K., Wei, H., Chen, W., Wang, W., Jia, L., Liu, Q., Zhang, J., Shan, T., Peng, Z., Liu, Y. & Yan, X. (2020). Dynamic relationship between D-dimer and COVID-19 severity. British Journal of Haematology, 190(1), 24–27. doi: 10.1111/bjh.16811.
Lim, S., Bae, J. H., Kwon, H. S. & Nauck, M. A. (2021). COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nature Reviews Endocrinology, 17(1), 11–30. doi: 10.1038/s41574-020-00435-4.
Long, H., Nie, L., Xiang, X., Li, H., Zhang, X., Fu, X., Ren, H., Liu, W., Wang, Q. & Wu, Q. (2020). D-Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID-19 and Poor Prognosis. BioMed Research International, 16;2020:6159720. doi: 10.1155/2020/6159720.
Marietta, M., Ageno, W., Artoni, A., De Candia, E., Gresele, P., Marchetti, M., Marcucci, R. & Tripodi A. (2020). COVID-19 and haemostasis: A position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfusion, 18(3), 167–169. doi: 10.2450/2020.0083-20.
McGonagle, D., O’Donnell, J. S., Sharif, K., Emery, P. & Bridgewood, C. (2020). Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. The Lancet Rheumatology, 2(7), 437–445. doi: 10.1016/S2665-9913(20)30121-1.
Miri, C., Charii, H., Bouazzaoui, M. A., Laouan, B. F., Boulouiz, S., Abda, N., Kouismi, H., Bazid, Z., Ismaili, N. & El Ouafi N. (2021). D-dimer Level and Diabetes in the COVID-19 Infection. Clinical and Applied Thrombosis/Hemostasis, 27(1), 1–4. doi: 10.1177/1 07602962 11045902.
Mishra, Y., Kumar, B. & Sourabh, S. (2020). Relation of D-dimer levels of COVID-19 patients with diabetes mellitus. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(6), 1927–1930. doi: 10.1016/j.dsx.2020.09.035.
Moccia, F., Gerbino, A., Lionetti, V., Miragoli, M., Munaron, L.M., Pagliaro, P., Pasqua, T., Penna, C., Rocca, C., Samaja, M. & Angelone, T. (2020). COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches. GeroScience, 42(4), 1021–1049. doi: 10.1007/s11357-020-00198-w.
Mueller, A. L., McNamara, M. S. & Sinclair, D. A. (2020). Why does COVID-19 disproportionately affect older people?. Aging, 12(10), 9959–9981. doi: 10.18632/aging.103344.
National Institutes of Health (2021). Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19). Nih, 2019, 1–243. Available at: https://www.covid19treatmentgu idelines.nih.gov/.%0Ahttps://www.covid19treatmentguidelin s.nih.gov/.
Sahni, S., Gupta, G., Sarda, R., Pandey, S. & Pandey, R. M. (2021). Impact of metabolic and cardiovascular disease on COVID-19 mortality: A systematic review and meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15 (102308) . doi.org/10.1016/j.dsx.2021.
Sharma, A., Garg, A., Rout, A. & Lavie, C. J. (2020). Association of Obesity With More Critical Illness in COVID-19. Mayo Clinic Proceedings, 95(9), 2040–2042. doi: 10.1016/j.mayocp.2020.06.046.
Shibata, S., Arima, H., Asayama, K., Hoshide, S., Ichihara, A., Ishimitsu, T., Kario, K., Kishi, T., Mogi, M., Nishiyama, A., Ohishi, M., Ohkubo, T., Tamura, K., Tanaka, M., Yamamoto, E., Yamamoto, K. & Itoh, H. (2020). Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19. Hypertension Research, 43(10), 1028–1046. doi: 10.1038/s41440-020-0515-0.
Tang, N., Li, D., Wang, X. & Sun, Z. (2020). Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis, 18(4), 844–847. doi: 10.1111/jth.14768.
Thachil, J., Tang, N., Gando, S., Falanga, A., Cattaneo, M., Levi, M., Clark, C. & Iba, T. (2020). ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis, 18(5), 1023–1026. doi: 10.1111/jth.14810.
Van Jaarsveld, G. M. (2020). The Effects of COVID-19 Among the Elderly Population: A Case for Closing the Digital Divide. Frontiers in Psychiatry, 11(1), 1–7. doi: 10.3389/fpsyt.2020.577427.
Xia, F., Zhang, M., Cui, B., An, W., Chen, M., Yang, P., Qin, T., Zhou, X., Liao, Y., Xu, X., Liu, S., Li, K., Zhou, Q., Wang, K., Hu, G., Du, M., Chen, S., Zhang, Y., Wei, W., Xiang, M. & Zhang, J. (2021). COVID-19 patients with hypertension are at potential risk of worsened organ injury. Scientific Reports, 11(1), 1–10. doi: 10.1038/s41598-021-83295-w.
Yang, Q., Zhou, Y., Wang, X., Gao, S., Xiao, Y., Zhang, W., Hu, Y. & Wang Y. (2020). Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis. Respiratory Research, 21(1), 172–181. doi: 10.1186/s12931-020-01435-8.
Zhang, Z., Wan, J., Zhu, S., Wang, M., Wang, X., Tong, X. & Ding, J. (2021). Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity. Medicina Clínica, 159(4), 171-176. doi: 10.1016/j.medcle.2021.09.030.
Zou, Y., Guo, H., Zhang, Y., Zhang, Z., Liu, Y., Wang, J., Lu, H. & Qian, Z. (2020). Analysis of coagulation parameters in patients with COVID-19 in Shanghai, China. BioScience Trends, 14(4), 285–289. doi: 10.5582/bst.2020.03086.
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Impact of age dominating over the pre-existing comorbidities influencing the D-Dimer levels in SARS-COV-2 infection. (2023). Journal of Applied and Natural Science, 15(1), 120-127. https://doi.org/10.31018/jans.v15i1.4231
