Serum extracellular vesicles profiling is associated with COVID-19 progression  and immune responses.

[en] Coronavirus disease 2019 (COVID-19) has transformed very quickly into a world pandemic with severe and unexpected consequences on human health. Concerted efforts to generate better diagnostic and prognostic tools have been ongoing. Research, thus far, has primarily focused on the virus itself or the direct immune response to it. Here, we propose extracellular vesicles (EVs) from serum liquid biopsies as a new and unique modality to unify diagnostic and prognostic tools for COVID-19 analyses. EVs are a novel player in intercellular signalling particularly influencing immune responses. We herein show that innate and adaptive immune EVs profiling, together with SARS-CoV-2 Spike S1(+) EVs provide a novel signature for SARS-CoV-2 infection. It also provides a unique ability to associate the co-existence of viral and host cell signatures to monitor affected tissues and severity of the disease progression. And provide a phenotypic insight into COVID-associated EVs.

Disciplines :

Laboratory medicine & medical technology
Immunology & infectious disease
Biotechnology

Author, co-author :

Yim, Kevin Ho Wai; Institute of Experimental Immunology University of Zurich Zurich Switzerland.

Borgoni, Simone; Institute of Experimental Immunology University of Zurich Zurich Switzerland.

CHAHWAN, Richard ; University of Luxembourg ; Institute of Experimental Immunology University of Zurich Zurich Switzerland.

External co-authors :

yes

Language :

English

Title :

Serum extracellular vesicles profiling is associated with COVID-19 progression and immune responses.

Publication date :

April 2022

Journal title :

Journal of Extracellular Biology

eISSN :

2768-2811

Publisher :

Wiley

Volume :

Issue :

Pages :

e37

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBilu :

since 20 March 2026

Statistics

Number of views

30 (0 by Unilu)

Number of downloads

10 (0 by Unilu)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Babatunde, K. A., Yesodha Subramanian, B., Ahouidi, A. D., Martinez Murillo, P., Walch, M., & Mantel, P. Y. (2020). Role of extracellular vesicles in cellular cross talk in malaria. Frontiers in Immunology, 11, 22. https://doi.org/10.3389/FIMMU.2020.00022
Balbi, C., Burrello, J., Bolis, S., Lazzarini, E., Biemmi, V., Pianezzi, E., Burrello, A., Caporali, E., Grazioli, L. G., Martinetti, G., Fusi-Schmidhauser, T., Vassalli, G., Melli, G., & Barile, L. (2021). Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection. EBioMedicine, 67, 103369.
Bernstein, K. E., Khan, Z., Giani, J. F., Cao, D. Y., Bernstein, E. A., & Shen, X. Z. (2018). Angiotensin-converting enzyme in innate and adaptive immunity. Nature Reviews Nephrology, 14, 325.
Birnhuber, A., Fliesser, E., Gorkiewicz, G., Zacharias, M., Seeliger, B., David, S., Welte, T., Schmidt, J., Olschewski, H., Wygrecka, M., & Kwapiszewska, G. (2021). Between inflammation and thrombosis: Endothelial cells in COVID-19. European Respiratory Journal, 2100377.
Cervia, C., Nilsson, J., Zurbuchen, Y., Valaperti, A., Schreiner, J., Wolfensberger, A., Raeber, M. E., Adamo, S., Weigang, S., Emmenegger, M., Hasler, S., Bosshard, P. P., De Cecco, E., Bächli, E., Rudiger, A., Stüssi-Helbling, M., Huber, L. C., Zinkernagel, A. S., Schaer, D. J., … Boyman, O. (2021). Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. Journal of Allergy and Clinical Immunology, 147, 545.
Cervia, C., Zurbuchen, Y., Taeschler, P., Adamo, S., Hasler, S., Raeber, M. E., Bächli, E., Rudiger, A., Stüssi-Helbling, M., Huber, L. C., Held, U., Nilsson, J., & Boyman, O. (2021). Immunoglobulin signature predicts risk of post-acute covid-19 syndrome. SSRN Electron Journal, https://doi.org/10.2139/ssrn.3850036
Cocozza, F., Névo, N., Piovesana, E., Lahaye, X., Buchrieser, J., Schwartz, O., Manel, N., Tkach, M., Théry, C., & Martin-Jaular, L. (2020). Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus. Journal of Extracellular Vesicles, 10(2), 12050. https://doi.org/10.1002/jev2.12050
de Jong, O. G., Verhaar, M. C., Chen, Y., Vader, P., Gremmels, H., Posthuma, G., Schiffelers, R. M., Gucek, M., & van Balkom, B. W. M. (2012). Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. Journal of Extracellular Vesicles, 1, https://doi.org/10.3402/jev.v1i0.18396
Dhar, S. K., Vishnupriyan, K., Damodar, S., Gujar, S., & Das, M. (2020). medRxiv, https://doi.org/10.1101/2020.08.15.20175844
Dong, E., Du, H., & Gardner, L. (2020). An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases, 20, 533.
Fujita, Y., Hoshina, T., Matsuzaki, J., Yoshioka, Y., Kadota, T., Hosaka, Y., Fujimoto, S., Kawamoto, H., Watanabe, N., Sawaki, K., Sakamoto, Y., Miyajima, M., Lee, K., Nakaharai, K., Horino, T., Nakagawa, R., Araya, J., Miyato, M., Yoshida, M., Kuwano, K., & Ochiya, T. (2021). Early prediction of COVID-19 severity using extracellular vesicle COPB2. Journal of Extracellular Vesicles, 10, e12092.
Galani, I. E., Rovina, N., Lampropoulou, V., Triantafyllia, V., Manioudaki, M., Pavlos, E., Koukaki, E., Fragkou, P. C., Panou, V., Rapti, V., Koltsida, O., Mentis, A., Koulouris, N., Tsiodras, S., Koutsoukou, A., & Andreakos, E. (2021). Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nature Immunology, 22, 32.
Hettich, B. F., Ben-Yehuda Greenwald, M., Werner, S., & Leroux, J. C. (2020). Exosomes for wound healing: Purification optimization and identification of bioactive components. Advance Science (Weinheim, Baden-Wurttemberg, Ger.), 7(23), 2002596. https://doi.org/10.1002/ADVS.202002596
Han, H., Ma, Q., Li, C., Liu, R., Zhao, L., Wang, W., Zhang, P., Liu, X., Gao, G., Liu, F., Jiang, Y., Cheng, X., Zhu, C., & Xia, Y. (2020). Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerging Microbes & Infections, 9, 1123.
Jin, M., Shi, N., Wang, M., Shi, C., Lu, S., Chang, Q., Sha, S., Lin, Y., Chen, Y., Zhou, H., Liang, K., Huang, X., Shi, Y., & Huang, G. (2020). CD45: A critical regulator in immune cells to predict severe and non-severe COVID-19 patients. Aging (Albany NY), 12, 19867.
Levy, J. H., Iba, T., & Gardiner, E. E. (2021). Endothelial injury in COVID-19 and acute infections. Arteriosclerosis, Thrombosis, and Vascular Biology, 41, 1774.
Lichtenauer, M., Goebel, B., Fritzenwanger, M., Förster, M., Betge, S., Lauten, A., Figulla, H. R., & Jung, C. (2015). Simulated temporary hypoxia triggers the release of CD31+/Annexin+ endothelial microparticles: A prospective pilot study in humans. Clinical Hemorheology and Microcirculation, 61, 83.
Lu, L., Zhang, H., Dauphars, D. J., & He, Y. W. (2021). A potential role of interleukin 10 in COVID-19 pathogenesis. Trends in Immunology, 42, 3.
Mao, K., Tan, Q., Ma, Y., Wang, S., Zhong, H., Liao, Y., Huang, Q., Xiao, W., Xia, H., Tan, X., Luo, P., Xu, J., Long, D., & Jin, Y. (2021). Proteomics of extracellular vesicles in plasma reveals the characteristics and residual traces of COVID-19 patients without underlying diseases after 3 months of recovery. Cell Death & Disease, 12, 541.
Martin, A., Chahwan, R., Parsa, J. Y., & Scharff, M. D. (2015). Somatic Hypermutation: The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. In F. W. Alt, T. Honjo, A. Radbruch, & M. Reth (Eds.), Molecular Biology of B Cells (2nd ed., pp. 363–388). Academic Press. https://doi.org/10.1016/B978-0-12-397933-9.00020-5
Merad, M., & Martin, J. C. (2020). Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nature Reviews Immunology, 20, 355.
Puelles, V. G., Lütgehetmann, M., Lindenmeyer, M. T., Sperhake, J. P., Wong, M. N., Allweiss, L., Chilla, S., Heinemann, A., Wanner, N., Liu, S., Braun, F., Lu, S., Pfefferle, S., Schröder, A. S., Edler, C., Gross, O., Glatzel, M., Wichmann, D., Wiech, T., … Huber, T. B. (2020). Multiorgan and renal tropism of SARS-CoV-2. New England Journal of Medicine, 383, 590.
Robinson, P. C., Richards, D., Tanner, H. L., & Feldmann, M. (2020). Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment. Lancet Rheumatology, 2, e653.
Silva, A. M., Lázaro-Ibáñez, E., Gunnarsson, A., Dhande, A., Daaboul, G., Peacock, B., Osteikoetxea, X., Salmond, N., Friis, K. P., Shatnyeva, O., Dekker, N. (2021). Quantification of protein cargo loading into engineered extracellular vesicles at single-vesicle and single-molecule resolution. Journal of Extracellular Vesicles, 10(10), e12130. https://doi.org/10.1002/JEV2.12130
Sheppard, E. C., Morrish, R. B., Dillon, M. J., Leyland, R., & Chahwan, R. (2018). Epigenomic modifications mediating antibody maturation. Frontiers in Immunology, 9, 355. https://doi.org/10.3389/fimmu.2018.00355
Tian, Y., Gong, M., Hu, Y., Liu, H., Zhang, W., Zhang, M., Hu, X., Aubert, D., Zhu, S., Wu, L., & Yan, X. (2020). Quality and efficiency assessment of six extracellular vesicle isolation methods by nano-flow cytometry. Journal of Extracellular Vesicles, 9(1), 1697028. https://doi.org/10.1080/20013078.2019.1697028
Troyer, Z., Alhusaini, N., Tabler, C. O., Sweet, T., Carvalho, K. I. L., Schlatzer, D. M., Carias, L., King, C. L., Matreyek, K., & Tilton, J. C. (2021). Extracellular vesicles carry SARS-CoV-2 spike protein and serve as decoys for neutralizing antibodies. Journal of Extracellular Vesicles, 10, e12112.
Veettil, M. V., Kumar, B., Ansari, M. A., Dutta, D., Iqbal, J., Gjyshi, O., Bottero, V., & Chandran, B. (2016). ESCRT-0 component Hrs promotes macropinocytosis of Kaposi's sarcoma-associated herpesvirus in human dermal microvascular endothelial cells. Journal of Virology, 90, 3860.
Vidarsson, G., Dekkers, G., & Rispens, T. (2014). IgG subclasses and allotypes: From structure to effector functions. Frontiers in Immunology, 5, 520. https://doi.org/10.3389/fimmu.2014.00520
Vitte, J., Diallo, A. B., Boumaza, A., Lopez, A., Michel, M., Allardet-Servent, J., Mezouar, S., Sereme, Y., Busnel, J. M., Miloud, T., Malergue, F., Morange, P. E., Halfon, P., Olive, D., Leone, M., & Mege, J. L. (2020). Journal of Infectious Diseases, 222, 1985.
Walsh, K. A., Spillane, S., Comber, L., Cardwell, K., Harrington, P., Connell, J., Teljeur, C., Broderick, N., de Gascun, C. F., Smith, S. M., Ryan, M., & O'Neill, M. (2020). The duration of infectiousness of individuals infected with SARS-CoV-2. Journal of Infection, 81, 847.
Welsh, J. A., Van Der Pol, E., Arkesteijn, G. J. A., Bremer, M., Brisson, A., Coumans, F., Dignat-George, F., Duggan, E., Ghiran, I., Giebel, B., Görgens, A., Hendrix, A., Lacroix, R., Lannigan, J., Libregts, S. F. W. M., Lozano-Andrés, E., Morales-Kastresana, A., Robert, S., De Rond, L., … Jones, J. C. (2020). Journal of Extracellular Vesicles, 9(1), 1816641. https://doi.org/10.1002/cyto.a.20623
World Health Organization. (2020). Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020. World Health Organization. https://apps.who.int/iris/handle/10665/330893
World Health Organization. (2020). Criteria for releasing COVID-19 patients from isolation: scientific brief, 17 June 2020. World Health Organization. https://apps.who.int/iris/handle/10665/332451
Wu, Z., & McGoogan, J. M. (2020). Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China. JAMA - Journal of the American Medical Association, 323, 1239.
Yim, K. H. W., Al Hrout, A., Borgoni, S., & Chahwan, R. (2020). Extracellular vesicles orchestrate immune and tumor interaction networks. Cancers (Basel), 12(12), 3969.