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A group from Beijing Proteome Research Center, etc. has reported results of quantitative and comparative urine proteome analysis from healthy individuals, mild and severe COVID-19 positive patients.
https://pubmed.ncbi.nlm.nih.gov/33688631/

A total number of 2656 proteins was identified from healthy control samples. There were 1008 proteins being commonly identified and quantified among healthy, mild and sever cases. However, 211 and 63 proteins were uniquely expressed in COVID-19 patients and recovery samples.

Some proteins increased in COVID-19, but some proteins decrease inversely in COVID-19.
Typical examples are listed below. However, from a view point of this blog Admin, there is some question if urine proteome can be used as a diagnostic tool, because it seems that urine proteome can not discriminate severity of COVID-19 from moderate, mild, to sever. But, it would definitely contribute to elucidation of COVID-19 pathology. The fact that the urine proteome of recovered patients is not the same as healthy individuals would suggest that the aftereffects are remaining for a longer time.

IGLV1-40: 14 times higher in the severe COVID-19
FKBP1A: 13 times higher in the severe COVID-19
LUNA: 37 times higher in the severe COVID-19
PARK7: 7 times higher in the severe COVID-19

CD9: 1/12 times lower in the sever COVID-19
EGF: 1/25 times lower in the sever COVID-19
MME: 1/18 times lower in the sever COVID-19
CUBN: 1/19 times lower in the sever COVID-19

A group from Amsterdam UMC, etc. has reported on mechanisms of immune modulations in pancreatic ductal adenocarcinoma (PDAC) through aberrant glycan modification, especially upregulated α2-3 sialic acids.
https://www.nature.com/articles/s41467-021-21550-4.pdf

PDAC is surrounded by dense fibrotic stroma and suppressive immune cells, mostly of the myeloid lineage such as dendric cells and macrophages (called TME). It has been known that aberrant glycosylation changes in PDAC are upregulation of sialyl Lewis^x, sialyl Lewis^a, truncated O-glycans, increased branched and fucosylated N-glycans, and are related to tumor cell proliferation, invasion, metastasis, and inflammation. However, their detailed link to the immune cell function in PDAC is still unknown.

Authors have deep dived into the link between the aberrant sialylation and immune cells, and further its relationship with survival rate of PDAC. Composition of myeloid linkage cells composing TMA is greatly different between PDAC and healthy tissues. In PDAC, monocyte-derived macrophages (moMac) and monocyte-derived dendritic cells (moDC) accounted for the majority of the composition. Interestingly, patients with a higher presence of moMac over moDC had shorter survival, and the other myeloid populations did not correlate with the survival rate.

It was clearly shown that upregulated α2-3Sia bound to Siglec-7 and Siglec-9 expressed on myeloid cells, and drove the differentiation of monocytes to moMac with upregulation of CD206. Further, these changes induced upregulation of immune check point molecule PD-L1 and secretion of immunosuppressive cytokines such as IL-10.

A group from University of California, San Francisco, etc. has reported recently emergent SARS-CoV-2 variants in San Francisco Bay area from Nov. 2020 to Jan. 2021.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941666/

In the Bay Area, it seems that B.1.427 and B.1.429 variants are dominant. Please refer to the figure below (L452R, S13I, W152C are major spike mutations). Additional studies are required to understand differences between those variants.

A group from Nagoya Univ. has identified a counter-receptor of Siglec-7.
https://www.jbc.org/article/S0021-9258(21)00251-9/fulltext

Siglec-7 binds to sialic acids and are expressed on natural killer (NK) cells and monocytes. Siglec-7 suppress cytotoxicity of NK cells through interaction with a counter-receptor on it. However, the counter-receptor of Siglec-7 has not been identified yet completely. Authors purified the receptor with using K562 cells, FC-Siglec-7 fusion protein, diSia-dextran polymer, and identified it as leukosialin (CD43) with MS analysis. Additionally, they demonstrated that the cytotoxicity of NK cells toward K562 cells was suppressed by overexpression of leukosialin in a Siglec-7-dependent manner.
 

A group from Harvard Univ. and Emory Univ. has reported on the interaction between ABO(H) blood group and SARS-CoV-2 RBD.
https://ashpublications.org/bloodadvances/article/5/5/1305/475250/The-SARS-CoV-2-receptor-binding-domain

It has been suggested that SARS-CoV-2 NTD might be bid to ABO(H) blood antigens, because SARS-CoV-2 RBD shares sequence similarity with a galectin family. Authors have confirmed that SARS-CoV-2 RBD could bind to A blood type I antigen expressed on respiratory epithelium cells with using glycan arrays.

A group from University of Ferrara, etc. has reported on the difference in biomarkers between ICU patients with COVID-19-related ARDS and classical ARDS.
https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03499-4

Evaluated marker were as follow, Receptor for Advanced Glycation End Products (RAGE), Angiopoietin-2 (Ang-2)、soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), E-Selectin, and P-Selectin.

Ang-2 is a growth factor (glycoprotein) promoting vascularization,
ICAM-1 is a member of immunoglobulin superfamily and a ligand for activated leukocytes,
VCAM-1 functions as a cell adhesion molecule like ICAM-1, but is usually not expressed on endothelial cells, and needs IL-1, TNF-α stimulations,
E-Selectin is a leukocyte-endothelial cell adhesion molecule expressed on vascular endothelial cells,
P-Selectin is a leukocyte adhesion molecule, and expressed in platelets and vascular endothelial cells.

RAGE has almost no relationship with COVDI-19 suggesting that the ARDS is caused by virus infection. Ang-2, ICAM-1, BVCAM-1, and E-Selectin are higher in COVID-19 (P-Selectin is lower on the contrary) suggesting that vascular endothelial cells are heavily damaged in ICU patients of COVID-19. 

On a blog article posted on Feb. 19th, 2021, it was reported that new variants (Q677H, Q677P) are increasing from the end of the last year in North America.

A group from Univ. of Bern, etc. has reported on the effect of Q677 variants on SARS-CoV-2 infectivity with using a SWISS MODEL.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885944/

The S1/S2 cleavage site contains the multibasic cleavage site (RRAR Motif). Although the position 677 is outside the polybasic site (furin binding pocket), the presence of a proline at this site may introduce a favorable kink that promotes the dynamic conformational changes necessary for cleavage at the S1/S2 junction, which is governed not only by furin-like activities, but also by trypsin-like proteases (e.g., TMPRSS2) and cathepsins. Moreover, the introduction of a proline in this model appears to be 3.7 angstroms away from the carbon backbone of S689 (relative to 4.9 angstroms for the native glutamine), which may promote atomic interactions that encourage conformations favorable for proteolytic cleavage. In the case of the S:Q677H substitution, histidine protonation could similarly act as a conformational switch affecting accessibility to proteases. These conformational changes may accelerate virus infection. 

In the new coronavirus (COVID-19), there is a broad spectrum of disease severity from asymptomatic to severe. How the immune reaction is different in the disease spectrum? There are so many studies are ongoing in the world to uncover this problem. A group from Third Military Medical University, Chongqing, China, etc. has reported there is a clear difference in the balance of humoral immunity and cellular immunity between asymptomatic/mild and moderate/severe.
https://www.nature.com/articles/s41392-021-00525-3

Let’s classify disease severity into two categories, asymptomatic/mild and moderate/severe. In the case of asymptomatic/mild, the expression of SARS-CoV-2 specific IgG is weak and transiently terminated without developing germinal center. In contrast, in the case of moderate/sever, the expression of SARS-CoV-2 specific IgG increases greatly and circulating cT_FH cells and chemokine CXCL13, which indicate the magnitude of ongoing germinal center, are upregulated, suggesting that the humoral immunity is strongly activated.
On the other hand, in the case of asymptomatic/mild, IFN-γ producing CD8+ T cells、SARS-CoV-2 specific T_H1 cells, Granzyme B（GZMB）are greatly upregulated, suggesting that cellular immunity is strongly activated. (Granzyme B（GZMB）is a Serine Protease expressed on cytoplasmic granules of activated cytotoxic T cells and NK cells, and induce apoptosis of target cells)

That is, asymptomatic/mild is a result of SARS-CoV-2 infection suppression with activate cytotoxic T-cells and NK cells (not mentioned here), and if the viruses are not cleared with this process, the humoral immunity comes to the front to combat viruses, or we can say that it is a result of the balance between humoral immunity and cellular immunity.
Further, recent studies found there exists cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2I. So, it is of great interest to examine whether the history of “common cold” coronavirus infection with pre-existing SARS-CoV-2 cross-reactive T cells could account for the clinically asymptomatic state in COVID-19 patients.