Abstract
The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
References
Bi, Y., Tan, S., Yang, Y., Wong, G., Zhao, M., Zhang, Q., Wang, Q., Zhao, X., Li, L., Yuan, J., et al. (2019). Clinical and immunological characteristics of human infections with H5N6 avian influenza virus. Clin Infect Dis 68, 1100–1109.
Chan, J.F.W, Yuan, S., Kok, K.H., To, K.K.W, Chu, H., Yang, J., Xing, F., Liu, J., Yip, C.C.Y, Poon, R.W.S, et al. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet, https://doi.org/10.1016/S0140-6736(20)30154-9.
Crackower, M.A., Sarao, R., Oudit, G.Y., Yagil, C., Kozieradzki, I., Scanga, S.E., Oliveira-dos-Santos, A.J., da Costa, J., Zhang, L., Pei, Y., et al. (2002). Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417, 822–828.
Damman, K., Gori, M., Claggett, B., Jhund, P.S., Senni, M., Lefkowitz, M. P., Prescott, M.F., Shi, V.C., Rouleau, J.L., Swedberg, K., et al. (2018). Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure. JACC-Heart Failure 6, 489–498.
Forrester, S.J., Booz, G.W., Sigmund, C.D., Coffman, T.M., Kawai, T., Rizzo, V., Scalia, R., and Eguchi, S. (2018). Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology. Physiol Rev 98, 1627–1738.
Froch, H., Nelges, C., Tr, T., Schwenger, V., Cebola, R., Schnorbach, J., Goode, K.M., Kazmi, S., Katus, H.A., Cleland, J.G.F, et al. (2016). Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease. Am Heart J 178, 28–36.
Guo, J., Huang, F., Liu, J., Chen, Y., Wang, W., Cao, B., Zou, Z., Liu, S., Pan, J., Bao, C., et al. (2015). The serum profile of hypercytokinemia factors identified in H7N9-infected patients can predict fatal outcomes. Sci Rep 5, 10942.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, https://doi.org/10.1016/S0140-6736(20)30183-5.
Huang, F., Guo, J., Zou, Z., Liu, J., Cao, B., Zhang, S., Li, H., Wang, W., Sheng, M., Liu, S., et al. (2014). Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients. Nat Commun 5, 3595.
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., et al. (2005). Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 11, 112–116.
Jiang, Y., Xu, J., Zhou, C., Wu, Z., Zhong, S., Liu, J., Luo, W., Chen, T., Qin, Q., and Deng, P. (2005). Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med 171, 850–857.
Ko, J.H., Park, G.E., Lee, J.Y., Lee, J.Y., Cho, S.Y., Ha, Y.E., Kang, C.I., Kang, J.M., Kim, Y.J., Huh, H.J., et al. (2016). Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients. J Infection 73, 468–475.
Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., et al. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11, 875–879.
Leem, A.Y., Park, B., Kim, Y.S., Jung, J.Y., and Won, S. (2018). Incidence and risk of chronic obstructive pulmonary disease in a Korean community-based cohort. Int J Chron Obstruct Pulmon Dis 13, 509 517.
Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K. S.M., Lau, E.H.Y, Wong, J.Y., et al. (2020). Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med, https://doi.org/10.1056/NEJMoa2001316.
Lin, Y.C., Lin, J.W., Wu, M.S., Chen, K.C., Peng, C.C., and Kang, Y.N. (2017). Effects of calcium channel blockers comparing to angiotensinconverting enzyme inhibitors and angiotensin receptor blockers in patients with hypertension and chronic kidney disease stage 3 to 5 and dialysis: A systematic review and meta-analysis. PLoS ONE 12, e0188975.
Liu, C.L., Lu, Y.T., Peng, M.J., Chen, P.J., Lin, R.L., Wu, C.L., and Kuo, H. T. (2004). Clinical and laboratory features of severe acute respiratory syndrome vis-a-vis onset of fever. Chest 126, 509–517.
Mortensen, E.M., Nakashima, B., Cornell, J., Copeland, L.A., Pugh, M.J., Anzueto, A., Good, C., Restrepo, M.I., Downs, J.R., Frei, C.R., et al. (2012). Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumoniarelated outcomes. Clin Infect Dis 55, 1466–1473.
Murray, J.F., Matthay, M.A., Luce, J.M., and Flick, M.R. (1988). An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138, 720–723.
Niu, P., Zhao, G., Deng, Y., Sun, S., Wang, W., Zhou, Y., and Tan, W. (2018). A novel human mAb (MERS-GD27) provides prophylactic and postexposure efficacy in MERS-CoV susceptible mice. Sci China Life Sci 61, 1280–1282.
Packer, M., and McMurray, J.J.V. (2017). Importance of endogenous compensatory vasoactive peptides in broadening the effects of inhibitors of the renin-angiotensin system for the treatment of heart failure. Lancet 389, 1831–1840.
Rai, A.K., Sanjukta, S., and Jeyaram, K. (2017). Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension. Crit Rev Food Sci Nutrit 57, 2789–2800.
Tan, W., Zhao, X., Ma, X., Wang, W., Niu, P., Xu, W., Gao, G.F., and Wu, G. (2020). A novel coronavirus genome identified in a cluster of pneumonia cases Wuhan, China 2019–2020. China CDC Weekly 2, 61–62.
Torres, V.E., Abebe, K.Z., Chapman, A.B., Schrier, R.W., Braun, W.E., Steinman, T.I., Winklhofer, F.T., Brosnahan, G., Czarnecki, P.G., Hogan, M.C., et al. (2014). Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371, 2267–2276.
Vincent, J.L., Dubois, M.J., Navickis, R.J., and Wilkes, M.M. (2003). Hypoalbuminemia in acute illness: is there a rationale for intervention?. Ann Surgery 237, 319–334.
Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., Zhong, W., and Hao, P. (2020). 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, https://doi.org/10.1007/s11427-020-1637-5.
Yan, Y.W., Liu, Q., Li, N., Du, J.C., Li, X., Li, C., Jin, N.Y., and Jiang, C.Y. (2015). Angiotensin II receptor blocker as a novel therapy in acute lung injury induced by avian influenza A H5N1 virus infection in mouse. Sci China Life Sci 58, 208–211.
Yang, Y., Wong, G., Yang, L., Tan, S., Li, J., Bai, B., Xu, Z., Li, H., Xu, W., Zhao, X., et al. (2019). Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings. J Infection 78, 241–248.
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med, doi: https://doi.org/10.1056/NEJMoa2001017.
Zou, Z., Yan, Y., Shu, Y., Gao, R., Sun, Y., Li, X., Ju, X., Liang, Z., Liu, Q., Zhao, Y., et al. (2014). Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun 5, 3594.
Acknowledgements
The authors would like to thank a scientist who insists on being anonymous. The authors would also like to thank Shunwang Li and Xiaoyun Li who helped data analysis and making figures and tables. This work was supported by the National Science and Technology Major Project (2017ZX10103011 and 2017ZX10204401), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2017-I2M-1-009), Shenzhen Science and Technology Research and Development Project (JCYJ20180504165549581 and JCYJ20170413141236903), China Postdoctoral Science Foundation (2019T120147).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Compliance and ethics The author(s) declare that they have no conflict of interest.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Liu, Y., Yang, Y., Zhang, C. et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci. China Life Sci. 63, 364–374 (2020). https://doi.org/10.1007/s11427-020-1643-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-020-1643-8
Keywords
- 2019-nCoV
- Angiotensin II
- ARDS