Archive 20/12/8

CD147 is also suspected as a route of infection in the new coronavirus (SARS-CoV-2)

In envelope-having viruses, the binding of receptors and envelope proteins on the cell membrane surface of the host cell initiates the infection. In the new coronavirus (SARS-CoV-2), it is generally recognized that ACE2 is its receptor. ACE2 is expressed in the liver, lungs, stomach, kidneys, and large intestine, but ACE2 expression in the lungs is rather low, and it is suspected that other infection routes exist in view of the severity of COVID-19. C-type lectins, which are widely expressed in immune cells, are also candidates, but the following groups indicate that CD147 can be an infection pathway.

The interaction between CD147 and S-protein has been verified by SPR and ELISA methods, and actual infection experiments using VeroE6 and BEAS-2B cells have also been conducted.
Infection through CD147 is said to be endocytosis, not cell membrane fusion, as an infection mechanism.

A disposable qPCR chip for detecting the new coronavirus (COVID-19)

A group of  Imperial College London has reported a prototype of a disposable new coronavirus (COVID-19) detecting qPCR chip. Of course, this chip can also be used for other infections.

The chip has a very simple structure and is built on a Si substrate (the size of the chip is about 1 cm square). The cost when manufactured with a Si 4-inch wafer was about 40 yen/chip, so it will certainly be disposable.
The temperature control of the chip is done by controlling electric current flowing in the Si substrate, and the detection is performed electrochemically using methylene blue (MB) as a redox reporter. Since MB acts also as an intercalator of DNA, the electrochemical current changes when DNA is amplified.

Obesity is dangerous in covid-19

A group of Jinyun People’s Hospital, China has reported a relationship between covid-19 and obesity.

Statistical analysis through 12,591 COVID-19 patients showed that the BODY Mass Index (BMI Index) in humans infected with covid-19 was higher than that of mild individuals (MD (average difference in BMI) of 2.48 kg/m2, 95% [2.00 to 2.96 kg/m2]CI). In addition, obesity was shown to be more likely to develop severer disease in the pathology of COVID-19, for example, ICU treatment (OR = 1.57, 95% [1.18–2.09]CI, ECMO use (OR = 2.13, 95% [1.10–4.14]CI).

Excessive infiltration of naïve B cells triggers severe coronavirus (COVID-19)

In patients with the new coronavirus (COVID-19), excessive infiltration of CD4+/CD8+ cells, plasma cells, and macrophages into lung tissues is common, which is believed to lead to severe damages to lung tissues and pulmonary fibrosis.
A group of the National Defense Medical Center, Taipei has reported that excessive infiltration of naïve B cells triggers  observed pathophysiology of COVID-19.

Possible mechanisms include:
COVID-19 causes the accumulation and activation of naïve B-cells in the mediastinal lymph nodes through activation of β2-integrin and α4β1 integrin. Excessive infiltration of naïve B-cells activated by SARS-CoV-2 S-proteins secretes large amounts of IgM and activates the humoral immune
response. This recruits a large amount of monocytes into lung tissues, and the monocytes differentiate to macrophages. The secreted IgM simultaneously activates the complement system, Fc receptors on dendritic cells, and macrophages, increasing the antigen presentation of SARS-CoV-2 and enhancing phagocytosis. In addition, an increase in antigen presentation of SARS-CoV-2 accelerates the extrafollicular response through stimulation of IL-12-dependent plasma cell differentiation in naïve B cell to produce more IgM , suppressing formation of germinal centers and B-cell proliferation.

In conclusion, the importance of therapies targeting naïve B-cells has been proposed.

Depletion in IgM Memory B cells correlates with severity in the new coronavirus (COVID-19)

In the new coronavirus (COVID-19), it is generally considered that impaired immune responses triggers unfavourable outcomes.
A group of Univ. of Pavia, Italy, suggests that the depletion of IgM Memory B cells is related to severe disease.

A median value of IgM Memory B cell numbers was 65.0/uL (IQR: 51.0 – 85.0/uL) in healthy people, whereas a median vale was 5.9/uL  (IQR: 2.1 – 13.9/uL) in COVID-19 patients. Although the number of COVID-19 patients assessed was as small as 66, but the depletion in IgM Memory B cells was correlated with severe disease.
There was no correlation between age, sex, and the depletion in IgM Memory B cells.

A potential glycan marker for hepatocellular carcinoma derived from HCV infection: bi-antennary N-type glycan with Core Fucose and Bi-secting GlcNAc

There is a research report on biomarkers of hepatocellular carcinoma with cirrhosis derived from HCV infection.

It has been concluded that A2G1(6)FB (bi-antennary N-type glycan with Core Fucose and Bisecting GlcNAc) could be an excellent glycan marker.




In the figure below, TNM stands for Tumor-node-metastasis, and TNM=1, TNM=2, TNM=3, and TNM=4 represent the stage of hepatocellular carcinoma. The existing markers, AFP, PIVKA-II, do not show a clear correlation with A2G1(6)FB, and show excellent potency as an HCC marker.

A good Indicator for determining covid-19 and influenza A/B

The initial symptoms of covid-19 and influenza are very similar.
Is RT-PCR or antibody testing the only way to distinguish between these two infections?

Sapienza Univ. of Rome’s group has reported that the absolute count of monocytes, a type of leukocyte, is a good discriminating index between the two.

If the absolute count of monocytes is 0.35×10^3/mL or more, COVID-19 can be distinguished from influenza A/B. AUC=0.68 (sensitivity=0.992, specificity=0.368)

This strongly suggests that covid-19 and influenza A/B have different immune responses.

S-protein or RBD-specific IgG is a key to recovering from covid-19 and completely eliminating viruses

From the laboratory tests of 1850 hospitalized COVID-19 patients in Wuhan, the following group discussed the dynamic changes in IgG to SARS-CoV-2. If the IgG level is low, the complete elimination of the virus becomes difficult, and thereby there is a chance that RT-PCR SARS-CoV-2 virus testing after recovery (i.e., after discharge) becomes positive.

Dynamic changes in IgG include:

  • In severe cases, IgG level tends to be delayed by nearly a week compared to those with mild cases.
  • In severe cases, the level of IgG is significantly higher, and even in the elderly, the level of IgG tends to be higher.
  • It should be noted that patients with low levels of IgG at the time of hospital discharge may positive with RT-PCR reteaching of SARS-CoV-2.

Identification of immune-related biomarkers associated with novel coronavirus (COVID-19) mortality

It has been established that cytokine storms are occurring in the severe case of covid-19, and there are many research studies about such changes in blood cytokine concentrations.
Some of the most noteworthy studies have already been introduced in this blog site.

This article introduces the results obtained from covid-19 patients in Italy.

Clinical parameters indicate that the increase of the neutrophil/lymphocyte ratio, LDH, CRP, and D-dimer correlates with mortality.

In this study, 66 types of cytokines in the blood were evaluated, suggesting that MCP-1/CCL2, sTNFRSF1A, MMP-9, NGAL, S100A9, sST2, IL-10, and IL-15 were deeply related to the serious disease of COVID-19.
As a site note,
MCP-1/CCP, sTNFRSF1A are NK-kB-dependent markers,
MMP-9, NGAL, S100A9 are derived from neutrophils,
sST2 is a septic marker,
IL-15 is associated with NK-cell activation and function,
IL-10 is a counteraction of severe pneumonia,
has been discussed as such.

As the mechanism of serious disease becomes more concrete, effective therapeutic drugs will be narrowed down.

In the new coronavirus (COVID-19), the role of immunonutrition is attracting attention as it becomes more severe in people over 65 years of age.

In the new coronavirus (COVID-19), immunonutrition is attracting attention so much, as it takes time to confirm the safety and efficacy of vaccines, and also because there are still no effective therapeutic drugs for COVID-19. In particular, the importance and urgency of immunonutrition research is increasing due to the high rate of severity in older people aged 65 and over.

The case fatality rate of COVID-19 increases with age. Reported rates are 0.2% for those aged 50-59, 0.4% for those aged 60-69, 1.3% for those aged 70-79, and 3.6% for those aged 80 and over.

Vitamin C, vitamin D, and zinc are the most important immunonutrition agents. The following is typical findings on each agent.

Role of vitamin C
Vitamin C has been confirmed to be effective in the treatment of pneumonia. Vitamin C is involved in maintaining and enhancing the activity of neutrophils, which are one of lymphocytes responsible for immune function, so it has the effect of enhancing immune function and resistance to viruses. In terms of potential mechanisms, it is well recognized that infectious diseases increase oxidative stress. Infections usually activate phagocytes that release active oxygen, which is an oxidising agent. Vitamin C becomes a well-known antioxidant that can cancel out these effects.

Role of vitamin D
Vitamin D receptors are expressed in many immune cells, and vitamin D is converted to 25 (OH) D3 in the liver and into an active form of 1,25 (OH) 2D3 in the function of immune cells. Vitamin D deficiency increases the risk of acute respiratory infections, and vitamin D metabolites are known to modulate the expression and secretion of inflammatory cytokines such as interferon IFN-γ, CXCL8, CXCL10 and chemokines, IL-6, and the tumor necrosis factor TNF-α.

The role of zinc
Zinc deficiency is known to cause impaired cellular immunity, including thymus atrophy with cd4+, CD8+ T-cell reduction, reduced peripheral blood lymphocyte count, reduced cytokine production from helper T-cells, reduced cytotoxic activity of NK cells, and inhibition of the formation of neutrophil extracellular traps (networks that bind to pathogens).

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