Abstract
COVID-19 infection is not restricted to respiratory system and is a multisystem inflammatory disease, involving complex interplay of immunological, inflammatory, coagulation cascades, age and co-morbidities manifested by elevated inflammatory markers, coagulation disorders and immunological dysfunction with variable clinical manifestations. The diagnostic gold standard RT-PCR test has frequent false negative results. Diagnosis of clinical COVID-19 infection among highly suspected RT-PCR negative moderate to severe cases were done by measurement of panel of diagnostic criteria from baseline routine blood test, inflammatory blood biomarkers, coagulation dysfunction and imaging studies. Further confirmation of diagnosis was made by testing of COVID-19 specific antibodies at appropriate follow up time. Artesunate have antiviral effects against SARS-CoV-2 in- vitro studies. Empirical IV bolus Artesunate therapy of clinical COVID-19 associate with faster resolution of symptoms and appears to be very effective with excellent safety profile; prevents disease progression, thereby reduces morbidity and mortality among clinically diagnosed moderate to severe COVID-19 patients.
Keywords: COVID-19, IV Artesunate, Inflammatory blood biomarkers, diagnosis, COVID-19 antibodies.
References
- Samprathi M, Jayashree M.Biomarkers in COVID-19: An up-To Date Review. Front. Pediatr. https://doi.org./10.3389/fped.2020.607647.
- Zou LR, Ruan F, Huang MX, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. NEJM. 2020; published online Feb 19. https://doi.org/ 10. 1056/ NEJM
- Huang CL, Wang YM, Li XW, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020. Published online Jan 24. https://doi.org/10.1016/ S0140-6736(20)30183-5.
- Yang Y, Yang M , Shen C et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019 nCov infection. Feb 17, 2020. https://www.medrxiv.org/content/10.1101/2020.02.11.20021493v2.
- Zhao J, Young Q, Wang H et al. Antibody response to SARS-CoV-2 in patients of novel coronavirus disease 2019. Cli Infect Dis.2020 March 28 (Eupub ahead of print).
- Steven Woloshin, Neeraj Patel, Aaron S, Kesselheim. False Negative Test for SARS-CoV-2 Infection- Challenges and Implications. NEJM. August 6, 2020; e38 (1-3) down loaded on Sept 23, 2020.
- Wang M, Wu Q, Xu WZ, et al. Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan. MedRxiv 2020; published online Feb 18. DOI: 10.1101/ 2020.02.12.20022327.
- Tong Zitek. The Appropriate use of testing for COVID-19.Western Journal of Emergency Medicine. May .2020; 21(3):470-472.
- Huang CL, Wang YM, Li XW, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020. Published online Jan 24.https://doi.org/ 10.1016/ S0140-6736(20)30183-5.
- Chen NS, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020. Published online Jan 29. https://doi.org/10.1016/ S0140-6736(20)30211-7.
- Fever, symptoms screening misses many coronavirus cases. Mindscape. Nov 12.2020.
- New study Adds to COVID-19 symptoms list. Medscape. Nov.9, 2020. https: //bitly3pcqjnp. American Journal of Emergency Medicine. Online. Nov 7, 2020.
- COVID-19 rapid guideline: managing the long-term effects of COVID-19. NICE guideline Published: 18 December 2020. www.nice.org.uk/ng188.
- JD Santotoribo, DN-Jurado, EL-Balsalobre. Evaluation of Routine blood Tests for Diagnosis of Suspected Coronavirus Disease 2019.Clinical Lab.9/2020 June 8; 66:xxxx. Doi.10.7754/Clin.Lab.2020.200522.
- L García de Guadiana-Romualdo et al. Characteristics and laboratory findings on admission to the emergency department among 2873 hospitalized patients with COVID-19: the impact of adjusted laboratory tests in multicenter studies. A multicenter study in Spain (BIOCOVID-Spain study). Scandinavian Journal of Clinical and Laboratory Investigation. https:// doi.org/ 10.1080/ 00365513. 2021.1881997.
- TP Velaran, CG Mayer. Mild versus severe COVID-19: Laboratory Markers. Int J Infect Dis.95 (2020):304-307.https://doi.org/10.1016/J.IJID.2020.04.061.
- B Sun, Y Feng, X Mo, P Zheng, Q Wang, P Li, P Peng et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerging Microbes & Infections.2020, VOL. 9: 941-948. https:// doi.org.10.1080/22221751.2020.1762515.
- J Wagner, A Dupent, S Larsal, B Cash, A Farooq. Absolute lymphocyte count is prognostic marker in COVID-19: A retrospective cohort review. Int J Lab Hematol.2020; 001-5.Wileyonline library.com/journal/ijih.
- Poggiali, D Zaino, P Immovilli, L Rovero, G Losi, et al. Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients.Clinica Chimica Acta 509 (2020) 135–138.
- Mei-ying Wu, L Yao, Yi Wang, Xin-yun Zhu, Xia-fang Wang, Pei-jun Tang and Cheng Chen. Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) Pneumonia. Respiratory Research (2020) 21:171. https://doi.org/10.1186/s12931-020-01427-8.
- BM Henry, G Aggarwal, J Wong, S Benoit, J Vikse, M Plebani, G Lippi. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. American Journal of Emergency Medicine 38 (2020) 1722–1726.https://doi.org/10.1016/j.ajem.2020.05.073.
- Bermejo-Martin JF, Almansa R, Menendez R, et al. Lymphopenia community acquired pneumonia as signature of severe COVID-19 infection. J Infect. 2020; 80(5):e23–e24.
- Wang J, Jiang M, Chen X, et al. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020; 108(1):17–41.
- S Kiss, N Gede, P Hegyi, D Németh, M Földi et al. Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID‑19: a systematic review and meta‑analysis.Medical Microbiology and Immunology (2021) 210:33–47. https:// doi.org /10.1007/s00430-020-00696-w.
- Y Tjendra, Abdulaziz F. Al Mana, Andrea P. Espejo, Y Akgun, Nicolas C. Millan et al. Predicting Disease Severity and Outcome in COVID-19 Patients. A Review of Multiple Biomarkers. Prognostic Biomarkers in Patients with COVID-19.Arch Pathol Lab Med. 2020; 144:1465–1474; doi:10.5858/arpa.2020-0471-SA.
- Fang Y, Zheng H, Xie J, Lin M, Ying I, Pang P, Ji W. Sensitivity of chest CT for COVID-19: Comparison to RT-PCR. Radiology.Feb19: 2020:200432. https:// pub.rsna.org/ doi. 10.1148 / radiol.2020.200432.
- AI T, Yang Z, Hou H, Zhan C,Lv W, Tao Q, Sun Z, Xia L. Correlation of chest CT and RT-PCR testing in coronavirus Disease 2019(COVID-19) in China. A report of 1014 cases.Radiology.2020, Feb 26:200642.https://pubs.rsna.org/doi.10.1148/radiol.2020200642.
- X Ren, Yan Liu, H Chen, Ei Liu, ZW Guo, Y Xhang et al. Application and optimization of RT-PCR in Diagnosis of SARS-CoV-2 infection. MedRxiv:https://www.medRxiv.org/content/doi.10.1101/2020.02.25.20027755v2.
- Zhao J, Yuong Q, Wang H et al. Antibody response to SARS-CoV-2 in patients of novel coronavirus disease 2019.Clin Infect Dis .2020 March 28 (Eupub ahead of preprint).
- Ruiyuan Cao, Hengrui Hu, Yufeng Li, Xi Wang, Mingyue Xu, Jia Liu. et al. Anti-SARS-CoV-2 Potential of Artemisinins In- Vitro. ACS Infect Dis. July 31, 2020. https://dx.doi.org/10.1021/acsinfecdis.0c005 22.
- Joon-Yong Bae, Gee Eun Lee, Heedo Park, Juyoung Cho, Yung-Eui Kim, Joo-Yeon Lee, Chung Ju, Won-Ki Kim, Jin Il Kim, Man-Seong Park. Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza. bioRxiv preprint doi: https://doi.org/10.1101/2020.07.28.225102; this version posted July 28, 2020.
- Ilett KF, Batty KT. Powell S. M Binh, T Q, Thu l., Phuong HL, Hung NC, Davis TM. The pharmacokinetic properties of intramuscular Artesunate and rectal Dihydroartemisinin in uncomplicated falciparum malaria. Br. J. Clin. Pharmacol.2002; 53, 23−30.
- Kevin T. Batty, Le Thi Anh Thu,Timothy M. E. Davis, Kenneth F. Ilett,Truong Xuan Mai,Nguyen Canh Hung,Nguyen Phuc Tien,Shane M. Powell, Huynh Van Thien,Tran Quang Binh & Nguyen Van Kim. A pharmacokinetic and pharmacodynamic study of intravenous vs oral artesunate in uncomplicated falciparum malaria. Br J Clin Pharmacol 1998; 45: 123–129.
- Gilmore K, Y Zhou Y, Ramirez S, Long V. Pham, Fahnøe U, et al, In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2, bioRxiv preprint doi: https:// doi.org./10.1101/2020.10.05.326637. October 5 2020.
- Gordi T, Xie R, Huong NV, Huong DX, Karlsson MO, Ashton M. A semi physiological pharmacokinetic model for artemisinin in healthy subjects incorporating autoinduction of metabolism and saturable first pass hepatic extraction.Br J Clin Pharmacol.2005; 59:189–98.
- Karbwang J , Na-Bangchang K, Thanavibut A, Molunto P. Plasma concentrations of artemether and its major plasma metabolite Dihydroartemisinin following a 5 day regimen of oral artemether in patients with uncomplicated falciparum malaria. Ann Trop Med Parsit.1998; 92:31-36.
- Li Q, Xie LH, Haeberle A, Zhang J, Weina P. The evaluation of radiolabel Artesunate in tissue distribution in rats and protein binding in human. Am J Trop Med Hyg.1006; 75:817-826.
- Li Q, Milhous WK, Weina PJ. Artemisinin in malaria therapy. Overseas press (India) Pvt. Ltd. First Edn.2003.p-10, 82, 84, 98.
- Qisui Li,Lowis R Catilena ,Kevin J Leary,George A,Saviolakis R,Scott Miller ,Victor Melendez,,Peter J Weina. Pharmacokinetic profiles of Artesunate after single intraveinous dose at 0.5.,1,2,4 and 8mg/kg in healthy volunteers; A phase I study. Am J tROP Med Hyg.81(4); 2009;pp-615-621.doi.10.4269/ajtmh.2009.09.0150.
- YM Bar-On, A Flamholz, R Phillips, R Milo. Science Forum. SARS-CoV-2 (COVID-19) by the numbers. eLife.2020; 9:e57309. DOI https://doi.org/10.7554/eLife.57309.p- 1- 15.
- Fehr AR, Periman S, (2015), Coronavirus: an overview of their replication and pathogenesis. Method Mol Biol.1282; 1-23.
- Pradhan B, Nanda BC, Pradhan G. JMSCR.08:10; October 2020.p-215-225.
- Lin Y,Wu F,Xie Z,Song X,Zhu X,Zhu Q, Wei J,Tan S,Liang L.Ging B L. Clinical study of Artesunate in the treatment of coronavirus disease 2019.Europe PMC. 01 Apr 2020, 32(4):417-420. DOI: 10.3760/cma.j.cn121430-2020031200412. PMID: 3252734.
Corresponding Author
Pradhan B