Proteomics of extracellular vesicles in plasma reveals the characteristics and residual traces of COVID-19 patients without underlying diseases after 3 months of recovery

Abstract

More and more patients suffered from Coronavirus disease 2019 (COVID-19) have got recovery gradually due to suitable intervention. Increasing data mainly studies the clinical characteristics of recovered COVID-19 patients, and their molecular changes especially proteome changes also play the same important role in understanding of biological characteristics of recovered COVID-19 patients as clinical characteristics do. In our study, we reported the whole lung-ground glass-CT value-average of mild/severe recovered patients 3 months after discharge without underlying diseases was significantly lower than that of healthy subjects. Then we isolated the extracellular vesicles (EVs) of plasma from 19 healthy subjects and 67 recovered COVID-19 patients. Mass Spectrometry was used to catalogue the proteins of these EVs compared to a defined group of controls. Identified 174 proteins were differentially expressed in the EVs of COVID-19 patients compared with healthy subjects, which involved in lipid metabolic process, response to cellular, and response to stress oxygen-containing compound. Besides, we identified several protein of plasma EVs in recovered patients associated with coagulation activity, inflammatory reaction, immune response, and low organ function. In addition, proteins correlating with clinical index such as alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were also detected. Moreover, we also identified many unique or characteristic associations found in the recovered COVID-19 patients, which especially involved the kidney, serum electrolyte levels, and inflammation functions. This finding suggests that monitoring the situation of recovered patients might be useful, especially the indexes of coagulation, inflammation, immunity, and organ function, which can prevent bleeding, reinfection and organ dysfunction.

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2

“…To further elaborate, we found enrichment of the complement proteins properdin, C1r, C5, C1q, C1QB, C4BPB, C4BPA, and C8A in the ChipEXO compared with exosomes from healthy donor plasma. Similar observations have been reported by Mao et al ( 22 ) and Sin Man Lam et al ( 47 ). Activation of the complement system is necessary to induce anti-SARS-CoV-2 immunity, yet it can also contribute to endothelial cell damage and multiorgan failure ( 48 , 49 ).…”

“…Through protein and RNA cargo, exosomes can convey information to distant remote cells upon uptake by endocytosis. Elegant studies by Mao et al ( 22 ) showed that the size distribution of exosomes from patients with SARS-CoV-2 infection was similar (55 to 145 nm) but the protein content varied with infection severity. There have been experimental models to study the immunomodulatory ( 23 , 24 ), tropic ( 25 ), and antifibrotic ( 26 ) activities of plasma-derived exosomes.…”

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

“…Aside from studied soluble immune factors like antibodies and cytokines, EVs are emerging as novel and potent intercellular signalling mediators. EV cargos are under study as predictive tools for COVID‐19 severity (Balbi et al., 2021 ; Fujita et al., 2021 ; Mao et al., 2021 ). However, such recent studies required mass spectrometry and RNA‐seq of EVs cargo which is not easy to convert into routine clinical diagnostics due to the tedious processing and high expertise required.…”

“…EV cargos are under study as predictive tools for COVID-19 severity (Balbi et al, 2021;Fujita et al, 2021;Mao et al, 2021). However, such recent studies required mass spectrometry and RNA-seq of EVs cargo which is not easy to convert into routine clinical diagnostics due to the tedious processing and high expertise required.…”

Liver Dysfunction in COVID-19: From Onset to Recovery

“…For patients in severe condition, international normalized ratio decreased during the process of recovery, while TBIL increased. 89 During the recovery, the outlier ratio of ALT, AST, and GGT remained high within the 14 days after discharge, but decreased significantly at 40 days after discharge. Meanwhile, the outlier ratio of ALP remained high during the follow-up period.…”