• This record comes from PubMed

Complex Immunometabolic Profiling Reveals the Activation of Cellular Immunity and Biliary Lesions in Patients with Severe COVID-19

. 2020 Sep 17 ; 9 (9) : . [epub] 20200917

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article

Grant support
NV18-05-00162 Agentura Pro Zdravotnický Výzkum České Republiky
NU20-05-00320 Agentura Pro Zdravotnický Výzkum České Republiky

This study aimed to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients that are associated with mild, moderate, severe, and fatal courses of the disease, and through a longitudinal follow-up, to understand the dynamics of the COVID-19 pathophysiology. All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. A severe course of COVID-19 was associated with an elevation of proinflammatory markers; an efflux of immature granulocytes into peripheral blood; the activation of CD8 T cells, which infiltrated the lungs; transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with a severe form of the disease. In contrast, patients with a fatal course of COVID-19 failed to upregulate markers of inflammation, showed discoordination of the immune response, and progressed toward acute kidney failure. COVID-19 is a disease with a multi-organ affinity that is characterized by the activation of innate and cellular adaptive immunity. Biliary lesions with an elevation of GGT and the organ infiltration of interleukin 6 (IL-6)-producing cells are the defining characteristics for patients with the fulminant disease.

See more in PubMed

World Health Organization Coronavirus Disease (COVID-19) Pandemic. [(accessed on 15 September 2020)]; Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

ECDC COVID-19 Pandemic. [(accessed on 15 September 2020)]; Available online: https://www.ecdc.europa.eu/en/covid-19-pandemic.

Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. PubMed DOI PMC

Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;6736:1–9. doi: 10.1016/S0140-6736(20)30566-3. PubMed DOI PMC

Zhang J., Dong X., Cao Y., Yuan Y., Yang Y., Yan Y., Akdis C.A., Gao Y. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75:1730–1741 all.14238. doi: 10.1111/all.14238. PubMed DOI

Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir. Med. 2020;8:475–481. doi: 10.1016/S2213-2600(20)30079-5. PubMed DOI PMC

Chen T., Wu D., Chen H., Yan W., Yang D., Chen G., Ma K., Xu D., Yu H., Wang H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020;368:m1091. doi: 10.1136/bmj.m1091. PubMed DOI PMC

Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Biochem. Biophys. Res. Commun. 2020;525:135–140. doi: 10.1016/j.bbrc.2020.02.071. PubMed DOI PMC

Letko M., Marzi A., Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 2020;5:562–569. doi: 10.1038/s41564-020-0688-y. PubMed DOI PMC

Shang J., Wan Y., Luo C., Ye G., Geng Q., Auerbach A., Li F. Cell entry mechanisms of SARS-CoV-2. Proc. Natl. Acad. Sci. USA. 2020;117:11727–11734. doi: 10.1073/pnas.2003138117. PubMed DOI PMC

Chai X., Hu L., Zhang Y., Han W., Lu Z., Ke A., Zhou J., Shi G., Fang N., Fan J., et al. Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. bioRxiv. 2020 doi: 10.1101/2020.02.03.931766. DOI

Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S., Mehra M.R., Schuepbach R.A., Ruschitzka F., Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–1418. doi: 10.1016/S0140-6736(20)30937-5. PubMed DOI PMC

Xu H., Zhong L., Deng J., Peng J., Dan H., Zeng X., Li T., Chen Q. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int. J. Oral Sci. 2020;12:1–5. doi: 10.1038/s41368-020-0074-x. PubMed DOI PMC

Zou X., Chen K., Zou J., Han P., Hao J., Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020;14:185–192. doi: 10.1007/s11684-020-0754-0. PubMed DOI PMC

Radzikowska U., Ding M., Tan G., Zhakparov D., Peng Y., Wawrzyniak P., Wang M., Li S., Morita H., Altunbulakli C., et al. Distribution of ACE2, CD147, CD26 and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy. 2020 doi: 10.1111/all.14429. PubMed DOI PMC

Puelles V.G., Lütgehetmann M., Lindenmeyer M.T., Sperhake J.P., Wong M.N., Allweiss L., Chilla S., Heinemann A., Wanner N., Liu S., et al. Multiorgan and Renal Tropism of SARS-CoV-2. N. Engl. J. Med. 2020 doi: 10.1056/NEJMc2011400. PubMed DOI PMC

Ackermann M., Verleden S.E., Kuehnel M., Haverich A., Welte T., Laenger F., Vanstapel A., Werlein C., Stark H., Tzankov A., et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N. Engl. J. Med. 2020;383:120–128. doi: 10.1056/NEJMoa2015432. PubMed DOI PMC

Carsana L., Sonzogni A., Nasr A., Rossi R.S., Pellegrinelli A., Zerbi P., Rech R., Colombo R., Antinori S., Corbellino M., et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: A two-centre descriptive study. Lancet Infect. Dis. 2020 doi: 10.1016/S1473-3099(20)30434-5. PubMed DOI PMC

Li D., Chen Y., Liu H., Jia Y., Li F., Wang W., Wu J., Wan Z., Cao Y., Zeng R. Immune dysfunction leads to mortality and organ injury in patients with COVID-19 in China: Insights from ERS-COVID-19 study. Signal Transduct. Target. Ther. 2020;5:62. doi: 10.1038/s41392-020-0163-5. PubMed DOI PMC

Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin. Infect. Dis. 2020;2019:4–10. doi: 10.2139/ssrn.3541136. PubMed DOI PMC

Cao X. COVID-19: Immunopathology and its implications for therapy. Nat. Rev. Immunol. 2020;20:269–270. doi: 10.1038/s41577-020-0308-3. PubMed DOI PMC

Gong J., Dong H., Xia S.Q., Huang Y.Z., Wang D., Zhao Y., Liu W., Tu S., Zhang M., Wang Q., et al. Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia. medRxiv. 2020 doi: 10.1101/2020.02.25.20025643. PubMed DOI PMC

Zhang B., Zhou X., Zhu C., Feng F., Qiu Y., Feng J., Jia Q., Song Q., Zhu B., Wang J. Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19. medRxiv. 2020 doi: 10.3389/fmolb.2020.00157. PubMed DOI PMC

Tan M., Liu Y., Zhou R., Deng X., Li F., Liang K., Shi Y. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology. 2020 doi: 10.1111/imm.13223. PubMed DOI PMC

Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8:420–422. doi: 10.1016/S2213-2600(20)30076-X. PubMed DOI PMC

Zheng H.Y., Zhang M., Yang C.X., Zhang N., Wang X.C., Yang X.P., Dong X.Q., Zheng Y.T. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell. Mol. Immunol. :2020. doi: 10.1038/s41423-020-0401-3. PubMed DOI PMC

Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 2020:7–9. doi: 10.1038/s41423-020-0402-2. PubMed DOI PMC

Jain V., Yuan J.-M. Predictive symptoms and comorbidities for severe COVID-19 and intensive care unit admission: A systematic review and meta-analysis. Int. J. Public Health. 2020 doi: 10.1007/s00038-020-01390-7. PubMed DOI PMC

Li X., Xu S., Yu M., Wang K., Tao Y., Zhou Y., Shi J., Zhou M., Wu B., Yang Z., et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J. Allergy Clin. Immunol. 2020 doi: 10.1016/j.jaci.2020.04.006. PubMed DOI PMC

Skevaki C., Fragkou P.C., Cheng C., Xie M., Renz H. Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus. J. Infect. :2020. doi: 10.1016/j.jinf.2020.06.039. PubMed DOI PMC

Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S., Huang H., Zhang L., Zhou X., Du C., et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern. Med. 2020;180:934–943. doi: 10.1001/jamainternmed.2020.0994. PubMed DOI PMC

Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323:1061. doi: 10.1001/jama.2020.1585. PubMed DOI PMC

Roederer M., Nozzi J.L., Nason M.C. SPICE: Exploration and analysis of post-cytometric complex multivariate datasets. Cytom. Part A. 2011;79:167–174. doi: 10.1002/cyto.a.21015. PubMed DOI PMC

Zhang Y., Zheng L., Liu L., Zhao M., Xiao J., Zhao Q. Liver impairment in COVID‐19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int. 2020 doi: 10.1111/liv.14455. PubMed DOI

Thi Hong Nguyen C., Kambe N., Kishimoto I., Ueda-Hayakawa I., Okamoto H. Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement. J. Dermatol. 2017;44:789–797. doi: 10.1111/1346-8138.13792. PubMed DOI

Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S., Gommers D.A.M.P.J., Kant K.M., Kaptein F.H.J., van Paassen J., Stals M.A.M., Huisman M.V., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020;191:145–147. doi: 10.1016/j.thromres.2020.04.013. PubMed DOI PMC

Wilk A.J., Rustagi A., Zhao N.Q., Roque J., Martínez-Colón G.J., McKechnie J.L., Ivison G.T., Ranganath T., Vergara R., Hollis T., et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. 2020;26:1070–1076. doi: 10.1038/s41591-020-0944-y. PubMed DOI PMC

Moratto D., Chiarini M., Giustini V., Serana F., Magro P., Roccaro A.M., Imberti L., Castelli F., Notarangelo L.D., Quiros-Roldan E. Flow Cytometry Identifies Risk Factors and Dynamic Changes in Patients with COVID-19. J. Clin. Immunol. 2020 doi: 10.1007/s10875-020-00806-6. PubMed DOI PMC

Pan X., Baldauf H.M., Keppler O.T., Fackler O.T. Restrictions to HIV-1 replication in resting CD4 + T lymphocytes. Cell Res. 2013;23:876–885. doi: 10.1038/cr.2013.74. PubMed DOI PMC

Zhang Y., Wang X., Li X., Xi D., Mao R., Wu X., Cheng S., Sun X., Yi C., Ling Z., et al. Potential contribution of increased soluble IL-2R to lymphopenia in COVID-19 patients. Cell. Mol. Immunol. 2020;17:878–880. doi: 10.1038/s41423-020-0484-x. PubMed DOI PMC

Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: Management and challenges. Lancet Gastroenterol. Hepatol. 2020;5:428–430. doi: 10.1016/S2468-1253(20)30057-1. PubMed DOI PMC

Bangash M.N., Patel J., Parekh D. COVID-19 and the liver: Little cause for concern. Lancet Gastroenterol. Hepatol. 2020;5:529–530. doi: 10.1016/S2468-1253(20)30084-4. PubMed DOI PMC

Cai Q., Huang D., Yu H., Zhu Z., Xia Z., Su Y., Li Z., Zhou G., Gou J., Qu J., et al. COVID-19: Abnormal liver function tests. J. Hepatol. 2020 doi: 10.1016/j.jhep.2020.04.006. PubMed DOI PMC

Yang L., Han Y., Nilsson-Payant B.E., Gupta V., Wang P., Duan X., Tang X., Zhu J., Zhao Z., Jaffré F., et al. 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. 2020;S1934–S5909:30282–30284. doi: 10.1016/j.stem.2020.06.015. PubMed DOI PMC

Cheng Y., Luo R., Wang K., Zhang M., Wang Z., Dong L., Li J., Yao Y., Ge S., Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:829–838. doi: 10.1016/j.kint.2020.03.005. PubMed DOI PMC

Su H., Yang M., Wan C., Yi L.X., Tang F., Zhu H.Y., Yi F., Yang H.C., Fogo A.B., Nie X., et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98:219–227. doi: 10.1016/j.kint.2020.04.003. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...