Pengaruh Peningkatan Jaringan Adiposa pada Pasien Obesitas Terhadap Tingkat Keparahan Pasien Covid-19

Annas Adimara, Kartika Prahasanti, Kartika Prahasanti, Muhammad Perdana Airlangga, Muhammad Perdana Airlangga

Abstract


Penyakit COVID-19 telah menjadi pandemi global sejak Desember 2019. Menurut WHO, hingga 28 September 2020, sudah ada 33.137.748 kasus yang dikonfirmasi di seluruh dunia, 3,01% di antaranya meninggal dunia (998.372). Dengan Case Fatality sebesar 3,17% WHO menetapkan Wabah COVID-19 ini di tingkat pandemi. Dari 2,5 juta kematian akibat Covid-19 yang dilaporkan pada akhir Februari 2021, 2,2 juta lebih dari setengah populasinya diklasifikasikan sebagai kelebihan berat badan. Obesitas menjadi salah komorbid yang dikaitkan dengan keparahan gejala COVID-19 dikarenakan Obesitas sendiri dapat menyebabkan gejala seperti gangguan cardiovaskular, gangguan respirasi, gangguan imun, dan juga inflamasi kronis. Tujuan penelitian ini untuk mengetahui pengaruh peningkatan jaringan adiposa pada pasien obesitas terhadap tingkat keparahan pasien COVID-19.


Keywords


COVID-19, Obesitas, Jaringan Adiposa, Tingkat Keparahan

Full Text:

PDF

References


Abu-Raya, B. (2020). Predictors of refractory coronavirus disease (COVID-19) pneumonia. Clinical Infectious Diseases, 71(15), 895–896. https://doi.org/10.1093/cid/ciaa409

Amit Kumar Mandal , Paulami Dam , Octavio L. Franco , Hanen Sellami , Sukhendu Mandal , Gulten Can Sezgin , Kinkar Biswas , Partha Sarathi Nandi, I. O. (2020). Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-. Ann Oncol, January, 19–21.

Aylward, B., & Liang, W. (2020). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). The WHO-China Joint Mission on Coronavirus Disease 2019, 2019(February), 16–24. https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

Birsoy, K., & Laplante, M. (2013). A comparative perspective on lipid storage in animals Role of autophagy in the metabolic and inflammatory changes induced by obesity in C57BL6/J mice View project. Article in Journal of Cell Science. https://doi.org/10.1242/jcs.104992

Bixby, H., Bentham, J., Zhou, B., Di Cesare, M., Paciorek, C. J., Bennett, J. E., Taddei, C., Stevens, G. A., Rodriguez-Martinez, A.,

Borghi, F., Sevá-Pessôa, B., & Grassi-Kassisse, D. M. (2016). The adipose tissue and the involvement of the renin–angiotensin–aldosterone system in cardiometabolic syndrome. In Cell and Tissue Research (Vol. 366, Issue 3, pp. 543–548). Springer Verlag. https://doi.org/10.1007/s00441-016-2515-6

Carrillo-Larco, R. M., Khang, Y. H., Sorić, M., Gregg, E. W., Miranda, J. J., Bhutta, Z. A., Savin, S., Sophiea, M. K., Iurilli, M. L. C., Solomon, B. D., … Ezzati, M. (2019). Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature, 569(7755), 260–264. https://doi.org/10.1038/s41586-019-1171-x

Caci, G., Albini, A., Malerba, M., Noonan, D. M., Pochetti, P., & Polosa, R. (2020). COVID-19 and Obesity: Dangerous Liaisons. Journal of Clinical Medicine, 9(8), 2511. https://doi.org/10.3390/jcm9082511

Cai, Q., Chen, F., Wang, T., Luo, F., Liu, X., Wu, Q., He, Q., Wang, Z., Liu, Y., Liu, L., Chen, J., & Xu, L. (2020). Obesity and COVID-19 Severity in a Designated Hospital in Shenzhen, China. Diabetes Care, 43(7), 1392–1398. https://doi.org/10.2337/dc20-0576

Cardone, M., Yano, M., Rosenberg, A. S., & Puig, M. (2020).

Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation. Frontiers in Immunology, 11(December 2019).

https://doi.org/10.3389/fimmu.2020.01131

CDC. (2020). Overweight & Obesity | CDC. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/index.html

Chiappetta, S., Sharma, A. M., Bottino, V., & Stier, C. (2020). COVID-19 and the role of chronic inflammation in patients with obesity. International Journal of Obesity, 44(8), 1790–1792. https://doi.org/10.1038/s41366-020-0597-4

Cui, J., Li, F., & Shi, Z. L. (2019). Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 17(3), 181–192. https://doi.org/10.1038/s41579-018-0118-9

De Wit, E., Van Doremalen, N., Falzarano, D., & Munster, V. J. (2016). SARS and MERS: Recent insights into emerging coronaviruses. Nature Reviews Microbiology, 14(8), 523–534. https://doi.org/10.1038/nrmicro.2016.81

Dong, Y., Dong, Y., Mo, X., Hu, Y., Qi, X., Jiang, F., Jiang, Z., Jiang, Z., Tong, S., Tong, S., & Tong, S. (2020). Epidemiology of COVID-19 among children in China. Pediatrics, 145(6). https://doi.org/10.1542/peds.2020-0702

Dugail, I., Amri, E. Z., & Vitale, N. (2020). High prevalence for obesity in severe COVID-19: Possible links and perspectives towards patient stratification. Biochimie. https://doi.org/10.1016/j.biochi.2020.07.001

Elliot, J. G., Donovan, G. M., Wang, K. C. W., Green, F. H. Y., James, A. L., & Noble, P. B. (2019). Fatty airways: Implications for obstructive disease. European Respiratory Journal, 54(6). https://doi.org/10.1183/13993003.00857-2019

Emanuela, F., Grazia, M., Marco, D. R., Maria Paola, L., Giorgio, F., & Marco, B. (2012). Inflammation as a link between obesity and metabolic syndrome. In Journal of Nutrition and Metabolism (Vol. 2012). https://doi.org/10.1155/2012/476380

Fruh, S. M. (2017). Obesity: Risk factors, complications, and strategies for sustainable long-term weight management. Journal of the American Association of Nurse Practitioners, 29, S3–S14. https://doi.org/10.1002/2327-6924.12510

Gao, F., Zheng, K. I., Wang, X. B., Sun, Q. F., Pan, K. H., Wang, T. Y., Chen, Y. P., Targher, G., Byrne, C. D., George, J., & Zheng, M. H. (2020). Obesity Is a Risk Factor for Greater COVID-19 Severity. Diabetes Care, 43(7), E72–E74. https://doi.org/10.2337/dc20-0682

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052

Hussain, A., Mahawar, K., Xia, Z., Yang, W., & EL-Hasani, S. (2020). Obesity and mortality of COVID-19. Meta-analysis. Obesity Research and Clinical Practice, 14(4), 295–300. https://doi.org/10.1016/j.orcp.2020.07.002

Iacobellis, G. (2015). Local and systemic effects of the multifaceted epicardial adipose tissue depot. In Nature Reviews Endocrinology (Vol. 11, Issue 6, pp. 363–371). Nature Publishing Group. https://doi.org/10.1038/nrendo.2015.58

Jing, F., Mogi, M., & Horiuchi, M. (2013). Role of renin-angiotensin-aldosterone system in adipose tissue dysfunction. In Molecular and Cellular Endocrinology (Vol. 378, Issues 1–2, pp. 23–28). Elsevier. https://doi.org/10.1016/j.mce.2012.03.005

Kawabe, Y., Mori, J., Morimoto, H., Yamaguchi, M., Miyagaki, S., Ota, T., Tsuma, Y., Fukuhara, S., Nakajima, H., Oudit, G. Y., &

Hosoi, H. (2019). ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue. American Journal of Physiology - Endocrinology and Metabolism, 317(6), E1140–E1149.

https://doi.org/10.1152/AJPENDO.00311.2019

Kemenkes RI. (2020). Situasi Terkini Perkembangan (COVID-19). Kemenkes, September, 17–19. https://covid19.kemkes.go.id/download/Situasi_Terkini_050520.pdf

Kruger, P., Saffarzadeh, M., Weber, A. N. R., Rieber, N., Radsak, M., von Bernuth, H., Benarafa, C., Roos, D., Skokowa, J., & Hartl, D. (2015). Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury. In PLoS Pathogens (Vol. 11, Issue 3, pp. 1–22). Public Library of Science. https://doi.org/10.1371/journal.ppat.1004651

Kruglikov, I. L., & Scherer, P. E. (2020). The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections. Obesity, 28(7), 1187–1190. https://doi.org/10.1002/oby.22856

Kwok, S., Adam, S., Ho, J. H., Iqbal, Z., Turkington, P., Razvi, S., Le Roux, C. W., Soran, H., & Syed, A. A. (2020). Obesity: A critical risk factor in the COVID ‐19 pandemic . Clinical Obesity, 10(6), 1–11. https://doi.org/10.1111/cob.12403

Lal, S. K. (2010). Molecular biology of the SARS-coronavirus. Molecular Biology of the SARS-Coronavirus, 1–328. https://doi.org/10.1007/978-3-642-03683-5

Le Bert, N., Tan, A. T., Kunasegaran, K., Tham, C. Y. L., Hafezi, M., Chia, A., Chng, M. H. Y., Lin, M., Tan, N., Linster, M., Chia, W. N., Chen, M. I. C., Wang, L. F., Ooi, E. E., Kalimuddin, S., Tambyah, P. A., Low, J. G. H., Tan, Y. J., & Bertoletti, A. (2020). SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature, 584(7821), 457–462. https://doi.org/10.1038/s41586-020-2550-z

Leal, V. de O., & Mafra, D. (2013). Adipokines in obesity. Clinica Chimica Acta, 419, 87–94. https://doi.org/10.1016/j.cca.2013.02.003

Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P., Pan, P., Wang, W., Hu, D., Liu, X., Zhang, Q., & Wu, J. (2020). Coronavirus infections and immune responses. Journal of Medical Virology, 92(4), 424–432. https://doi.org/10.1002/jmv.25685

Louie, J. K., Acosta, M., Samuel, M. C., Schechter, R., Vugia, D. J., Harriman, K., & Matyas, B. T. (2011). A novel risk factor for a novel virus: Obesity and 2009 pandemic influenza a (H1N1). Clinical Infectious Diseases, 52(3), 301–312. https://doi.org/10.1093/cid/ciq152

Luther, J. M., Luo, P., Kreger, M. T., Brissova, M., Dai, C., Whitfield, T. T., Kim, H. S., Wasserman, D. H., Powers, A. C., & Brown, N. J. (2011). Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia, 54(8), 2152–2163. https://doi.org/10.1007/s00125-011-2158-9

Maier, H. E., Lopez, R., Sanchez, N., Ng, S., Gresh, L., Ojeda, S., Burger-Calderon, R., Kuan, G., Harris, E., Balmaseda, A., & Gordon, A. (2018). Obesity increases the duration of influenza a virus shedding in adults. Journal of Infectious Diseases, 218(9), 1378–1382. https://doi.org/10.1093/infdis/jiy370

Malavazos, A. E., Goldberger, J. J., & Iacobellis, G. (2020). Does epicardial fat contribute to COVID-19 myocardial inflammation? In European Heart Journal (Vol. 41, Issue 24, p. 2333). Oxford University Press. https://doi.org/10.1093/eurheartj/ehaa471

McLaughlin, T., Craig, C., Liu, L. F., Perelman, D., Allister, C., Spielman, D., & Cushman, S. W. (2016). Adipose cell size and regional fat deposition as predictors of metabolic response to overfeeding in insulin-resistant and insulin-sensitive humans. Diabetes, 65(5), 1245–1254. https://doi.org/10.2337/db15-1213

Mirsoian, A., Bouchlaka, M. N., Sckisel, G. D., Chen, M., Pai, C. C. S., Maverakis, E., Spencer, R. G., Fishbein, K. W., Siddiqui, S.,

Monjazeb, A. M., Martin, B., Maudsley, S., Hesdorffer, C., Ferrucci, L., Longo, D. L., Blazar, B. R., Wiltrout, R. H., Taub, D. D., & Murphy, W. J. (2014). Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. Journal of Experimental Medicine, 211(12), 2373–2383. https://doi.org/10.1084/jem.20140116

Moser, J. A. S., Galindo-Fraga, A., Ortiz-Hernández, A. A., Gu, W., Hunsberger, S., Galán-Herrera, J. F., Guerrero, M. L., Ruiz-Palacios, G. M., Beigel, J. H., Magaña-Aquino, M., Valdez-Vazquez, R.,

Moreno-Espinosa, S., Ramírez-Venegas, A., Llamosas-Gallardo, B., Pérez-Patrigeon, S., & Cherpitel, D. E. N. (2019). Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses. Influenza and Other Respiratory Viruses, 13(1), 3–9. https://doi.org/10.1111/irv.12618

NIH. (2020). Overweight and Obesity | NHLBI, NIH. https://www.nhlbi.nih.gov/health-topics/overweight-and-obesity

Pasquarelli-do-Nascimento, G., Braz-de-Melo, H. A., Faria, S. S.,

Santos, I. de O., Kobinger, G. P., & Magalhães, K. G. (2020). Hypercoagulopathy and Adipose Tissue Exacerbated Inflammation May Explain Higher Mortality in COVID-19 Patients With Obesity. In Frontiers in Endocrinology (Vol. 11, p. 530). Frontiers Media S.A. https://doi.org/10.3389/fendo.2020.00530

Patel, V. B., Mori, J., McLean, B. A., Basu, R., Das, S. K.,

Ramprasath, T., Parajuli, N., Penninger, J. M., Grant, M. B., Lopaschuk, G. D., & Oudit, G. Y. (2016). ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes, 65(1), 85–95. https://doi.org/10.2337/db15-0399

Patel, V. B., Zhong, J. C., Grant, M. B., & Oudit, G. Y. (2016). Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure. In Circulation Research (Vol. 118, Issue 8, pp. 1313–1326). Lippincott Williams and Wilkins. https://doi.org/10.1161/CIRCRESAHA.116.307708

Pinheiro, T. de A., Barcala-Jorge, A. S., Andrade, J. M. O., Pinheiro, T. de A., Ferreira, E. C. N., Crespo, T. S., Batista-Jorge, G. C., Vieira, C. A., Lelis, D. de F., Paraíso, A. F., Pinheiro, U. B., Bertagnolli, M., Albuquerque, C. J. B., Guimarães, A. L. S., de Paula, A. M. B., Caldeira, A. P., & Santos, S. H. S. (2017). Obesity and malnutrition similarly alters the renin–angiotensin system and inflammation in mice and human adipose. Journal of Nutritional Biochemistry, 48, 74–82.

https://doi.org/10.1016/j.jnutbio.2017.06.008

Popkin, B. M., Du, S., Green, W. D., Beck, M. A., Algaith, T., Herbst, C. H., Alsukait, R. F., Alluhidan, M., Alazemi, N., & Shekar, M. (2020). Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obesity Reviews, 21(11), 1–17. https://doi.org/10.1111/obr.13128

Robbins. (2012). Buku Ajar Patologi, Edisi 7. In Nasional (Vol. 2).

Roy, S., Mazumder, T., & Banik, S. (2020). The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms. SN Comprehensive Clinical Medicine, 2(8), 1077–1082. https://doi.org/10.1007/s42399-020-00376-z

Ryan, P. M., & Caplice, N. M. (2020). Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019? Obesity, 28(7), 1191–1194. https://doi.org/10.1002/oby.22843

Sherwood. (2016). Human Physiologi From Cell to Systems (Vol. 4, Issue 1).

Shimizu, I., & Walsh, K. (2015). The Whitening of Brown Fat and Its Implications for Weight Management in Obesity. Current Obesity Reports, 4(2), 224–229. https://doi.org/10.1007/s13679-015-0157-8

Smith, A. G., Sheridan, P. A., Harp, J. B., & Beck, M. A. (2007). Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. Journal of Nutrition, 137(5), 1236–1243. https://doi.org/10.1093/jn/137.5.1236

Synd, E. M., Bandaru, P., Rajkumar, H., & Nappanveettil, G. (2013). The Impact of Obesity on Immune Response to Infection and Vaccine: An Insight into Plausible Mechanisms. Endocrinol Metab Synd, 2(2). https://doi.org/10.4172/2161-1017.1000113

Teran-Cabanillas, E., Montalvo-Corral, M., Caire-Juvera, G., Moya-Camarena, S. Y., & Hernández, J. (2013). Decreased interferon-α and interferon-β production in obesity and expression of suppressor of cytokine signaling. Nutrition, 29(1), 207–212. https://doi.org/10.1016/j.nut.2012.04.019

Tim COVID-19 IDAI, & Covid-19, P. T. (2020). Protokol Tatalaksana Covid-19. 1, 1–50.

Tosepu, R., Gunawan, J., Effendy, D. S., Ahmad, L. O. A. I., Lestari, H., Bahar, H., & Asfian, P. (2020). Correlation between weather and Covid-19 pandemic in Jakarta, Indonesia. Science of the Total Environment, 725. https://doi.org/10.1016/j.scitotenv.2020.138436

Wagner, P. D. (2015). The physiological basis of pulmonary gas exchange: Implications for clinical interpretation of arterial blood gases. European Respiratory Journal, 45(1), 227–243. https://doi.org/10.1183/09031936.00039214

Whitmire, J. K. (2019). Tissue and Increases Vulnerability to Infection. 27(2), 514–524. https://doi.org/10.1016/j.celrep.2019.03.030.Obesity

WHO. (2020). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., Zhang, Y., Song, J., Wang, S., Chao, Y., Yang, Z., Xu, J., Zhou, X., Chen, D., Xiong, W., … Song, Y. (2020). Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine, 180(7), 934–943. https://doi.org/10.1001/jamainternmed.2020.0994

Yang, L., Han, Y., Nilsson-Payant, B. E., Gupta, V., Wang, P., Duan, X., Tang, X., Zhu, J., Zhao, Z., Jaffré, F., Zhang, T., Kim, T. W., Harschnitz, O., Redmond, D., Houghton, S., Liu, C., Naji, A., Ciceri, G., Guttikonda, S., … Chen, S. (2020). A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell, 27(1), 125-136.e7. https://doi.org/10.1016/j.stem.2020.06.015

Yao, X. H., He, Z. C., Li, T. Y., Zhang, H. R., Wang, Y., Mou, H., Guo, Q., Yu, S. C., Ding, Y., Liu, X., Ping, Y. F., & Bian, X. W. (2020). Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient. In Cell Research (Vol. 30, Issue 6, pp. 541–543). Springer Nature. https://doi.org/10.1038/s41422-020-0318-5

Zhang, Haibo, Penninger, J. M., Li, Y., Zhong, N., & Slutsky, A. S. (2020). Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine, 46(4), 586–590. https://doi.org/10.1007/s00134-020-05985-9

Zhang, Hongyan, Wang, L. L., Chen, Y. Y., Wu, Q., Chen, G., Shen, X., Wang, Q., Yan, Y., Yu, Y., Zhong, Y., Wang, X., Chua, M. L. K., Xie, C., Lippi, G., Mattiuzzi, C., Sanchis-Gomar, F., Henry, B. M., Yao, T., Gao, Y., … Azza. Y. et.al. (2020). Ce Pt Us Cr Ip T Ce Pt Us Cr T. Cancer, 46(May), 1–17. https://doi.org/10.1007/s00134-020-06023-4%0Ahttps://doi.org/10.1016/j.ijid.2020.03.053%0Ahttp://dx.doi.org/10.1016/S1470-2045(20)30310-7

Zhao, L. (2020). Obesity Accompanying COVID-19: The Role of Epicardial Fat. In Obesity (Vol. 28, Issue 8, p. 1367). Blackwell Publishing Inc. https://doi.org/10.1002/oby.22867

Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei, Y., Li, H., Wu, X., Xu, J., Tu, S.,

Zhang, Y., Chen, H., & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet, 395(10229), 1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3

Zhou, H., & Liu, F. (2018). Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4+ T Cells in the Control of Metabolic Homeostasis. Frontiers in Immunology, 9(August), 1961. https://doi.org/10.3389/fimmu.2018.01961

Zhu, Y., Jiang, M., Gao, L., & Huang, X. (2020). Single cell analysis of ACE2 expression reveals the potential targets for 2019-nCoV. https://doi.org/10.20944/preprints202002.0221.v1




DOI: http://dx.doi.org/10.30742/jikw.v10i2.1453

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Annas Adimara, Kartika Prahasanti, Kartika Prahasanti, Muhammad Perdana Airlangga, Muhammad Perdana Airlangga

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 
 

ISSN (Print): 1978-2071

E-ISSN (Online): 2580-5967

 

Editorial Office

Fakultas Kedokteran Universitas Wijaya Kusuma Surabaya
Jl. Dukuh Kupang XXV no 54 Surabaya, Indonesia

Gedung C lantai 2 (Ruang C216)
Telp. (+62) 31-5686531

Fax.  (+62) 31-5686531

email: jurnalkedokteranuwks@gmail.com

 


Jurnal Ilmiah Kedokteran Wijaya Kusuma by https://journal.uwks.ac.id/index.php/jikw/index  is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.