Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea
Min Hyuk Choi, Hyunmin Ahn, Han Seok Ryu, Byung-Jun Kim, Joonyong Jang, Moonki Jung, Jinuoung Kim, Seok Hoon Jeong
Journal of Clinical Medicine, doi:10.3390/jcm9061959
A rapid increase in the number of patients with coronavirus disease 19 (COVID-19) may overwhelm the available medical resources. We aimed to evaluate risk factors for disease severity in the early stages of COVID-19. The cohort comprised 293 patients with COVID-19 from 5 March 2020, to 18 March 2020. The Korea Centers for Disease Control and Prevention (KCDC) classification system was used to triage patients. The clinical course was summarized, including the impact of drugs (angiotensin II receptor blockers [ARB], ibuprofen, and dipeptidyl peptidase-4 inhibitors [DPP4i]) and the therapeutic effect of lopinavir/ritonavir. After adjusting for confounding variables, prior history of drug use, including ARB, ibuprofen, and DPP4i was not a risk factor associated with disease progression. Patients treated with lopinavir/ritonavir had significantly shorter progression-free survival than those not receiving lopinavir/ritonavir. KCDC classification I clearly distinguished the improvement/stabilization group from the progression group of COVID-19 patients (AUC 0.817; 95% CI, 0.740-0.895).
Author Contributions: Conceptualization, M.H.C., H.A., and S.H.J.; data curation, M.H.C. and H.A.; writingoriginal draft, M.H.C.; writing-review and editing, H.S.R., B.-J.K., J.J., M.J., and J.K. All authors have read and agreed to the published version of the manuscript.
Conflicts of Interest: The authors declare no conflicts of interest.
Appendix A
References
Brindley, Gold, Shnider, Oviedo, Gorman et al., Appraisal of methods for the study of chemotherapy of cancer in man: Comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide, J. Chronic Dis
Cao, Wang, Wen, Liu, Wang et al., A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2001282Charlson, Pompei, Ales, Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation, J. Chronic Dis,
doi:10.1016/0021-9681(87)90171-8Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study, Lancet,
doi:10.1016/S0140-6736(20)30211-7Deng, Peng, Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China, J. Clin. Med,
doi:10.3390/jcm9020575Ferrario, Jessup, Chappell, Averill, Brosnihan et al., Effect of angiotensin-converting enzyme inhibition and angiotensin ii receptor blockers on cardiac angiotensin-converting enzyme 2, Circulation,
doi:10.1161/CIRCULATIONAHA.104.510461Fine, Auble, Yealy, Hanusa, Weissfeld et al., A prediction rule to identify low-risk patients with community-acquired pneumonia, N. Engl. J. Med,
doi:10.1056/NEJM199701233360402Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2002032Guo, Wei, Zhang, Wu, Li et al., Clinical features predicting mortality risk in patients with viral pneumonia: The mulbsta score, Front. Microbiol,
doi:10.3389/fmicb.2019.02752Gurwitz, Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics, Drug Dev. Res,
doi:10.1002/ddr.21656Hill, Discussion of research using propensity-score matching: Comments on "A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003" by peter austin, statistics in medicine, Stat. Med,
doi:10.1002/sim.3245Hui, Azhar, Madani, Ntoumi, Kock et al., The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan, China, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.01.009Kim, Choe, Oh, Oh, Kim et al., The first case of 2019 novel coronavirus pneumonia imported into Korea from Wuhan, China: Implication for infection prevention and control measures, J. Korean Med. Sci,
doi:10.3346/jkms.2020.35.e61Li, Huang, Wang, Wang, Liang et al., COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis, J. Med. Virol,
doi:10.1002/jmv.25757Li, Wu, Wu, Guo, Chen et al., The clinical and chest CT features associated with severe and critical COVID-19 pneumonia, Investig. Radiol,
doi:10.1097/RLI.0000000000000672Lim, Van Der Eerden, Laing, Boersma, Karalus et al., Defining community acquired pneumonia severity on presentation to hospital: An international derivation and validation study, Thorax,
doi:10.1136/thorax.58.5.377Lu, Stratton, Tang, Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle, J. Med. Virol,
doi:10.1002/jmv.25678Mcmichael, Currie, Clark, Pogosjans, Kay et al., Epidemiology of COVID-19 in a long-term care facility in king county, Washington. N. Engl. J. Med,
doi:10.1056/NEJMoa2005412Peng, Meng, Guan, Leng, Zhu et al., Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV, Zhonghua Xin Xue Guan Bing Za Zhi
Qiao, Wang, Chen, Zhang, Liu et al., Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats, Cardiology,
doi:10.1159/000375362Richman, Whitley, Hayden, Clinical Virology
Shi, Yu, Zhao, Wang, Zhao et al., Host susceptibility to severe COVID-19 and establishment of a host risk score: Findings of 487 cases outside Wuhan, Crit. Care,
doi:10.1186/s13054-020-2833-7Vaduganathan, Vardeny, Michel, Mcmurray, Pfeffer et al., Renin-angiotensinaldosterone system inhibitors in patients with COVID-19, N. Engl. J. Med,
doi:10.1056/NEJMsr2005760Vankadari, Wilce, Emerging Wuhan (COVID-19) coronavirus: Glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26, Emerg. Microbes Infect,
doi:10.1080/22221751.2020.1739565Verdecchia, Angeli, Mazzotta, Ambrosio, Reboldi, Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of hypertension: Should they be used together?, Curr. Vasc. Pharmacol,
doi:10.2174/157016110793563924Vuille-Dit-Bille, Camargo, Emmenegger, Sasse, Kummer et al., Human intestine luminal ace2 and amino acid transporter expression increased by ace-inhibitors, Amino Acids,
doi:10.1007/s00726-014-1889-6Wan, Shang, Graham, Baric, Li, Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus, J. Virol,
doi:10.1128/JVI.00127-20Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA
Wyss, Girman, Locasale, Brookhart, Sturmer, Variable selection for propensity score models when estimating treatment effects on multiple outcomes: A simulation study, Pharmacoepidemiol. Drug Saf,
doi:10.1002/pds.3356Xiong, Sun, Liu, Fan, Zhao et al., Clinical and high-resolution CT features of the COVID-19 infection: Comparison of the initial and follow-up changes, Investig. Radiol,
doi:10.1097/RLI.0000000000000674Xu, Chen, Wang, Feng, Zhou et al., Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission, Sci. China Life Sci,
doi:10.1007/s11427-020-1637-5Young, Ong, Kalimuddin, Low, Tan et al., Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore, JAMA,
doi:10.1001/jama.2020.3204Zhang, Dong, Cao, Yuan, Yang et al., Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China, Allergy,
doi:10.1111/all.14238Zhao, Zhong, Xie, Yu, Liu, Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: A multicenter study, AJR Am. J. Roentgenol,
doi:10.2214/AJR.20.22976Zubrod, Schneiderman, Frei, Iii, None
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