Development and Approval of a Multidimensional Model of the Clinical Effectiveness of Treatment Technologies for Patients With a Mild COVID-19 Associated With Comorbidities

Authors

DOI:

https://doi.org/10.20535/ibb.2024.8.1.299055

Keywords:

coronavirus infection, mild COVID-19, aminocaproic acid, comorbidities, clinical effectiveness, multidimensional modeling

Abstract

Background. Today's latest infection, COVID-19, remains an urgent problem of the Ukrainian healthcare system, which requires further efforts to develop effective treatment strategies, especially considering the potential exacerbation of comorbidities.

Objective. Develop and approve a multivariate model of the effectiveness of the treating mild COVID-19 in patients with comorbidities, using Aminocaproic acid in comparison to nirmatrelvir/ritonavir and symptomatic therapy as examples.

Methods. The modeling was based on the results of a clinical study involving three groups of patients with mild COVID-19. Clinical symptoms and quality of life were dynamically evaluated through standardized questionnaires. Regression analysis was used to analyze the dynamics of clinical symptoms and identify general patterns and their correlation with quality of life.

Results. Modeling the dynamics of individual clinical symptoms allowed for the examination of recovery trends in mild COVID-19 patients under different drug treatments. Aminocaproic acid demonstrated a faster alleviation of primary respiratory symptoms compared to alternative treatments. Regression analysis highlighted that cough, sore throat, and general fatigue exert the most significant negative impact on the quality of life. These symptoms contribute to the decline in both physical and psychological health and limit activity during the disease course.

Conclusions. This study presents a novel, multidimensional model considering both the dynamics of individual clinical symptoms and patients' quality of life. The developed model was validated with retrospective data from mild COVID-19 patients with comorbidities. A multidimensional simulation of the clinical effectiveness of the use of aminocaproic acid, nirmatrelvir/ritonavir, or symptomatic treatment supports the preferential use of aminocaproic acid over other treatment methods. The quality-of-life modeling has enhanced our systematic understanding of the interplay between a set of clinical symptoms and overall patient condition, providing a rational foundation for treatment and care decisions.

References

Hariri LP, North CM, Shih AR, Israel RA, Maley JH, Villalba JA, Vinarsky V, et al. Lung histopathology in coronavirus disease 2019 as compared with severe acute respiratory sydrome and H1N1 influenza. Chest. 2021;159(1):73-84. DOI: 10.1016/j.chest.2020.09.259

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020;46(6):1099-102. DOI: 10.1007/s00134-020-06033-2

Chen Y, Klein SL, Garibaldi BT, Li H, Wu C, Osevala NM, et al. Aging in COVID-19: Vulnerability, immunity and intervention. Ageing Res Rev; 2021; 65:101205. DOI: 10.1016/j.arr.2020.101205

Machhi J, Herskovitz J, Senan AM, Dutta D, Nath B, Oleynikov MD, et al. The Natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections. J Neuroimmune Pharmacol. 2020;15(3):359-86. DOI: 10.1007/s11481-020-09944-5

Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603. DOI: 10.1001/jama.2020.12603

Lau HM, Lee EW, Wong CN, Ng GY, Jones AY, Hui DS. The impact of severe acute respiratory syndrome on the physical profile and quality of life. Arch Phys Med Rehabil. 2005;86(6):1134-40. DOI: 10.1016/j.apmr.2004.09.025

Lee AM, Wong JG, McAlonan GM, Cheung V, Cheung C, Sham PC, et al. Stress and psychological distress among SARS survivors 1 year after the outbreak. Can J Psychiatry. 2007;52(4):233-40. DOI: 10.1177/070674370705200405

Lam MH. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors. Arch Intern Med. 2009;169(22):2142. DOI: 10.1001/archinternmed.2009.384

Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113:45-57. DOI: 10.1007/s12185-020-03029-y

Serkedjieva J, Nikolova E, Kirilov N. Synergistic inhibition of Influenza A virus replication by a plant polyphenol-rich extract and ε-aminocaproic acid in vitro and in vivo. Acta Virol. 2010;54(2):137-45. DOI: 10.4149/av_2010_02_137

Sidorenko M, Dziublyk I, Soloviov S, Trokhimenko O, Dziublyk O, Smetiukh M, et al. In vitro study of the spectrum antiviral activity of aliphatic acid toward the prototype coronavirus strain. Biomed Biotechnol Res J. 2023;7(2):218. DOI: 10.4103/bbrj.bbrj_36_23

Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368(6489):409-12. DOI: 10.1126/science.abb3405

Ahmad B, Batool M, Ain QU, Kim MS, Choi S. Exploring the binding mechanism of PF-07321332 SARS-CoV-2 protease inhibitor through molecular dynamics and binding free energy simulations. Int J Mol Sci. 2021;22(17):9124. DOI: 10.3390/ijms22179124

Saravolatz LD, Depcinski S, Sharma M. Molnupiravir and nirmatrelvir-ritonavir: oral COVID antiviral drugs. Clin Infect Dis. 2023. DOI: 10.1093/cid/ciac180

Hart P. Relationship between muscular fitness, health behaviors, and health-related quality of life in U.S. Women. Am J Sports Sci Med. 2019;8(1):1-7. DOI: 10.12691/ajssm-8-1-1

Farag YM, Keithi-Reddy SR, Mittal BV, Surana SP, Addabbo F, Goligorsky MS, et al. Anemia, inflammation and health-related quality of life in chronic kidney disease patients. Clin Nephrol. 2011;75(06):524-33. DOI: 10.5414/cnp75524

Arab-Zozani M, Hashemi F, Safari H, Yousefi M, Ameri H. Health-related quality of life and its associated factors in COVID-19 patients. Osong public health and research perspectives. 2020;11(5):296. DOI: 10.24171/j.phrp.2020.11.5.05

Vallerand AH, Payne JK. Theories and conceptual models to guide quality of life related research. In: Quality of life: from nursing and patient perspectives. Jones & Bartlett Learning; 2003. p. 45-54.

Haas BK. A multidisciplinary concept analysis of quality of life. West J Nurs Res. 1999;21(6):728-42. DOI: 10.1177/01939459922044153

Mandzuk L, McMillan D. A concept analysis of quality of life. J Orthop Nurs. 2005;9(1):12-8. DOI: 10.1016/j.joon.2004.11.001

Taylor RM, Gibson F, Franck LS. A concept analysis of health-related quality of life in young people with chronic illness. J Clin Nurs. 2008;17(14):1823-33. DOI: 10.1111/j.1365-2702.2008.02379.x

Bakas T, McLennon SM, Carpenter JS, Buelow JM, Otte JL, Hanna KM, et al. Systematic review of health-related quality of life models. Health Qual Life Outcomes. 2012;10:134. DOI: 10.1186/1477-7525-10-134

Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmissions potential of COVID-19 infection in 9 pregnant women: a retrospective review of medical records. Obstet Anesthesia Dig. 2021;41(1):51. DOI: 10.1097/01.aoa.0000732568.92567.6e

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(11):1061. DOI: 10.1001/jama.2020.1585

Hui DS, Azhar EI, Madani TA, Ntoumi F, Kock R, Dar O, 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. 2020;91:264-6. DOI: 10.1016/j.ijid.2020.01.009

Marshall JC, Murthy S, Diaz J, Adhikari NK, Angus DC, Arabi YM, et al. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020;20(8):e192-7. DOI: 10.1016/s1473-3099(20)30483-7

Study of MK-4482 for prevention of coronavirus disease 2019 (covid-19) in adults (Mk-4482-013) (move-ahead) [Internet]. 2024 [cited 2023 Jul 12]. Available from: https://ichgcp.net/clinical-trials-registry/NCT04939428

Nirwati H, Donato CM, Ikram A, Aman AT, Wibawa T, Kirkwood CD, et al. Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia. J Med Virol. 2019;91(10):1776-87. DOI: 10.1002/jmv.25527

Soloviov SO, Hakim MS, Nirwati H, Aman AT, Soenarto Y, Pan Q, et al. Quality of symptom-based diagnosis of rotavirus infection based on mathematical modeling. In: Advances in Computer Science for Engineering and Education. Cham: Springer International Publishing; 2018. pp. 555-66. DOI: 10.1007/978-3-319-91008-6_56

Ang Q, Liu Z, Wang W, Li K. Explored research on data preprocessing and mining technology for clinical data applications. In: 2010 2nd IEEE International Conference on Information Management and Engineering. IEEE; 2010. pp. 327-30. DOI: 10.1109/ICIME.2010.5477660

Huang Y, Li W, Macheret F, Gabriel RA, Ohno-Machado L. A tutorial on calibration measurements and calibration models for clinical prediction models. J Am Med Inform Assoc. 2020;27(4):621-33. DOI: 10.1093/jamia/ocz228

Perzina R, Ramík J. Microsoft Excel as a tool for solving multicriteria decision problems. Procedia Comput Sci. 2014;35:1455-63. DOI: 10.1016/j.procs.2014.08.206

Sorino C, Negri S, Spanevello A, Visca D, Scichilone N. Inhalation therapy devices for the treatment of obstructive lung diseases: the history of inhalers towards the ideal inhaler. Eur J Intern Med. 2020;75:15-8. DOI: 10.1016/j.ejim.2020.02.023

Alipour S, Mahmoudi L, Ahmadi F. Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19. Drug Deliv Transl Res. 2023;13(3):705-15. DOI: 10.1007/s13346-022-01251-1

Yao Y, Wang H, Liu Z. Expression of ACE2 in airways: Implication for COVID‐19 risk and disease management in patients with chronic inflammatory respiratory diseases. Clin Amp Exp Allergy. 2020;50(12):1313-24. DOI: 10.1111/cea.13746

Liu N, Yang D, Zhang T, Sun J, Fu J, Li H. Systematic review and meta-analysis of olfactory and gustatory dysfunction in COVID-19. Int J Infect Dis. 2022;117:155-61. DOI: 10.1016/j.ijid.2022.02.004

Ari A, Rubin BK, Fink JB. Mesh nebulizers enabling transnasal pulmonary delivery of medical aerosols to infants and toddlers: Roles, challenges, and opportunities. Front Drug Deliv. 2022;2. DOI: 10.3389/fddev.2022.995489

George CE, Scheuch G, Seifart U, Inbaraj LR, Chandrasingh S, Nair IK, et al. COVID-19 symptoms are reduced by targeted hydration of the nose, larynx and trachea. Sci Rep. 2022;12(1). DOI: 10.1038/s41598-022-08609-y

Kong K, Chang Y, Qiao H, Zhao C, Chen X, Rong K, et al. Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis. J Transl Med. 2022;20(1). DOI: 10.1186/s12967-022-03770-4

Clauw DJ, Häuser W, Cohen SP, Fitzcharles MA. Considering the potential for an increase in chronic pain after the COVID-19 pandemic. Pain. 2020;161(8):1694-7. DOI: 10.1097/j.pain.0000000000001950

Coronavirus (COVID-19) update: FDA authorizes additional oral antiviral for treatment of COVID-19 in certain adults [Internet]. FDA; 2021 [cited 2023 Jul 12]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain

Wang F, Kream RM, Stefano GB. Long-term respiratory and neurological sequelae of COVID-19. Med Sci Monit. 2020;26. DOI: 10.12659/msm.928996

Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 2021;11(1). DOI: 10.1038/s41598-021-95565-8

Weldon IV EJ, Hong B, Hayashi J, Goo C, Carrazana E, Viereck J, et al. Mechanisms and severity of exercise intolerance following COVID-19 and similar viral infections: a comparative review. Cureus. 2023;15(5). DOI: 10.7759/cureus.39722

Al Maqbali M, Al Badi K, Al Sinani M, Madkhali N, Dickens GL. Clinical features of COVID-19 patients in the first year of pandemic: a systematic review and meta-analysis. Biol Res Nurs. 2022;24(2):172-85. DOI: 10.1177/10998004211055866

Gassen J, Nowak TJ, Henderson AD, Muehlenbein MP. Dynamics of temperature change during experimental respiratory virus challenge: Relationships with symptoms, stress hormones, and inflammation. Brain Behav Immun. 2022;99:157-65. DOI: 10.1016/j.bbi.2021.10.001

Qi R, Chen W, Liu S, Thompson PM, Zhang LJ, Xia F, et al. Psychological morbidities and fatigue in patients with confirmed COVID-19 during disease outbreak: prevalence and associated biopsychosocial risk factors. medRxiv [Preprint]. 2020 May 11:2020.05.08.20031666. DOI: 10.1101/2020.05.08.20031666

Vaidya A, Kleinegris MC, Severens JL, Ramaekers BL, Cate-Hoek AJ, Ten Cate H, et al. Comparison of EQ-5D and SF-36 in untreated patients with symptoms of intermittent claudication. J Comp Eff Res. 2018;7(6):535-48. DOI: 10.2217/cer-2017-0029

Hanmer J. Cross-sectional validation of the PROMIS-preference scoring system by its association with social determinants of health. Qual Life Res. 2021;30(3):881-9. DOI: 10.1007/s11136-020-02691-3

Mason AJ, Gomes M, Carpenter J, Grieve R. Flexible Bayesian longitudinal models for cost‐effectiveness analyses with informative missing data. Health Econ. 2021;30(12):3138-3158. DOI: 10.1002/hec.4408

Pinto M, Marotta N, Caracò C, Simeone E, Ammendolia A, de Sire A. Quality of life predictors in patients with melanoma: a machine learning approach. Front Oncol. 2022;12:843611. DOI: 10.3389/fonc.2022.843611

Norris CM, Ghali, WA, Saunders LD, Brant R, Galbraith D, Faris P. Ordinal regression model and the linear regression model were superior to the logistic regression models. J Clin Epidemiol. 2006;59(5):448-56. DOI: 10.1016/j.jclinepi.2005.09.007

Rudakova LO, Mikhalchuk VM. Characteristics of illness among healthcare employees. Clin Prevent Med. 2023;8:108-17. DOI: 10.31612/2616-4868.8.2023.13

Larsen JR, Martin MR, Martin JD, Kuhn P, Hicks JB. Modeling the onset of symptoms of COVID-19. Front Public Health. 2020;8:473. DOI: 10.3389/fpubh.2020.00473

Sribna OV, Kvasha OO. Risk reduction assessment: epidemiology and novel approaches. Clin Prevent Med. 2023;7:113-22. DOI: 10.31612/2616-4868.7.2023.15

Published

2024-02-26

How to Cite

1.
Yakovenko O, Soloviov S, Smetiukh M, Khanin O, Khodosh E, Dziublyk Y, Surtaieva N. Development and Approval of a Multidimensional Model of the Clinical Effectiveness of Treatment Technologies for Patients With a Mild COVID-19 Associated With Comorbidities. Innov Biosyst Bioeng [Internet]. 2024Feb.26 [cited 2024Dec.10];8(1):19-36. Available from: https://ibb.kpi.ua/article/view/299055

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