IL-1R7 antibody would be effective in COVID-19 to suppress cytokine storms

A group from University of Colorado Denver Anschutz Medical Campus has reported that IL-1R7 antibody would be effective in COVID-19 to suppress cytokine storms.
https://www.jbc.org/article/S0021-9258(21)00416-6/fulltext

Excessive inflammation observed in macrophage activation syndrome (MAS) results in severe diseases with high mortality. The cytokine storms observed in COVID-19 patients would be a typical example similar to MAS.
Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms

IL-18 binds its specific receptor IL-1 Receptor 5 (IL-1R5, also known as IL-18 Receptor alpha chain), leading to the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7, also known as IL-18 Receptor beta chain).

Authors found that the anti-IL-1R7 antibody significantly suppressed IL-18-mediated NFκB activation, IL-18-stimulated IFNγ production, and IL-6 production in human cell lines.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in COVID-19 patients 

A group from Juntendo University Faculty of Medicine has reported seroprevalence of IgG and IgM antibodies in COVID-19 patients, although the cohort size was small including only 34 patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023454/

Using a chemiluminescent microparticle immunoassay (CMIA)-based SARS-CoV-2 IgG test (cat. # 06R90, Abbott),
Severe/Critical cases:within a week after symptom onset=40%、1~2 weeks=88%、after two weeks=100%,
Mild/Moderate cases:within a week after symptom onset=0%、1~2 weeks=38%、after two weeks=100%.

Using an IC IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test (cat. # RTA0203, AutoBio),
Severe/Critical cases:within a week after symptom onset=60%、1~2 weeks=63%、after two weeks=100%,
Mild/Moderate cases:within a week after symptom onset=17%、1~2 weeks=63%、after two weeks=100%.

In this study, IgG titers remained at significantly elevated levels for 2 months, regardless of disease severity. These results indicate that IgG serologic tests could be used as a complementary test to PCR to diagnose COVID-19 from 14 days after symptom onset. However, since this cohort is so small without including asymptomatic individuals, a larger scale cohort is needed to conclude final answer.
     

Difference in site-specific glycosylation of SARS-CoV-2 spike proteins (all recombinants) among several laboratories

A group from University of Southampton, etc. has compared site-specific glycosylation of SARS-CoV-2 spike proteins (all recombinants) among five laboratories.
The cells used for Sproten expression were as follows.
HEK293: Amsterdam, Harvard,
HEK293F: Southampton/Texas,
HEK293T: Oxford,
CHO: Swiss,
It is celarly shown that site-specific glycosylation changes considerablly with reflecting differences in cells and culture conditions.
Fundamentally speaking, it is a mixture of oligo mannose and complex type N-glycans.

Blog admin is interested in how much these differences cause difference in the infectivity, how glycosylation changes with SARS-CoV-2 mutations, and how much the glycosylation changes due to mutations affect the infectivity.
https://www.biorxiv.org/content/10.1101/2021.03.08.433764v1.full

A cocktail monoclonal antibody (REGN-COV2) is unaffected by B.1.1.7, B.1.351, P.1 variants, however, the vaccine Pfizer BNT162b2 shows markedly reduced inhibition against B.1.351, P.1 variants 

A group from German Primate Center, Göttingen, etc. has reported on the effectiveness of major monoclonal antibodies for COVID-19 (Casirivimab, Bamlanivimab, Imdevimab)against SARS-CoV-2 variants, that of a cocktail monoclonal antibody (REGN-COV2: consisting of Casirivimab and Imdevimab), and also that of Pfizer BNT162b2 vaccine against those variants.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980144/

A cocktail monoclonal antibody (REGN-COV2)efficiently inhibited infection mediated by the S proteins of all variants (B.1.1.7, B.1.351, P.1). However, infection mediated by the S proteins of the B.1.351 and P.1 variant was completely resistant to REGN10989 and Bamlanivimab.

On the other hand, the Pfizer BNT162b2 vaccine is based on an mRNA that encodes for the SARS-CoV-2 S protein and is said to be highly protective against COVID-19. All sera from 15 donors immunized twice with BNT162b2 efficiently inhibited entry driven by the WT S protein and inhibition of entry driven by the S protein of the B.1.1.7 variant was only slightly reduced. However, 12 out of 15 sera showed a markedly reduced inhibition of entry driven by the S proteins of the B.1.351 and P.1 variants

 

Diagnostic accuracy of COVID-19 Chest CT images with using Deep Learning methodology

A group from Sejong University, Seoul, etc. has reported on the accuracy of COVID-19 diagnosis in chest CT images with applying Deep Learning.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249450

The neural network using in Deep Learning was composed of 20 stages, and convolution and pooling functions were incorporated. The resolution of the input images were (224 x 224, and the sizes of convolution were (3 x 3)and(5 x 5). The obtained overall accuracy was 99.83%(sensitivity=0.9286, specificity=0.99). In the future, it will be accelerate to adopt Deep Learning in diagnostic applications.

Using SARS-CoV-2 nanoparticles as a vaccine, a broadly neutralizing antibody strong to SARS-CoV-2 variants could be induced 

A group from Scripps Research Institute has reported that a broadly neutralizing antibody strong to SARS-CoV-2 variants could be induced by using SARS-CoV-2 nanoparticles as a vaccine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010731/

The main stream of the current vaccines is using platforms which deliver the recombinant SARS-CoV-2 spike as an antigen such as mRNA-encapsulated liposomes (e.g., BNT162b2 and mRNA-1273), adenovirus vectors (e.g., ChAdOx1 nCoV-19 [AZD1222], CTII-nCoV, Sputnik V, and Ad26.COV2.S). There vaccines are compatible with B.1.1.7 variant, but a notable loss of efficacy was reported for B.1.351 and P.1 variants. Therefore, it is required to develop vaccines that can elicit a broadly neutralizing antibody (bNAb) response to SARS-CoV-2 variants. For this purpose, those vaccines have to induce long-lived germinal center (GC) reactions to activate precursor B cells, stimulate affinity maturation, and form long-term immune memory.

The SARS-CoV-2 spike protein is a trimer of S1-S2 heterodimers. The S1 subunit contains a receptor-binding domain (RBD) to initiate infection. The S2 subunit consists of a fusion peptide (FP) and heptad repeat regions 1 and 2 (HR1 and HR2). Authors designed an HR2-deleted glycine-capped spike (S2GΔHR2) to increase the spike stability, and assembled those spikes on a nanoparticle platform called SApNP using I3–01v9 60-mers as a linker (S2GΔHR2-10GS-I3-01v9-LD7-PADRE (I3-01v9-L7P)). The I3–01v9-LP7 presents 20 stabilized spikes.

Using S2GΔHR2-10GS-I3-01v9-L7P as a vaccine, a bNAb were induced showing compatible titers for B.1.1.7, B.1.351, and P.1 variants. Compared with the soluble spike, this nanoparticle showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold higher germinal center reactions in lymph node follicles. The reason of this effect is not clear yet, but would be related to the size effect.

The effect of Transgenic Expression of Human C-Type Lectin CLEC18A in Aedes aegypti on suppressing Dengu Virus infectivity and proliferation

A group from National Health Research Institutes, Miaoli, Taiwan, etc. has established a transgenic Aedes aegypti line that expresses human CLEC18A, and has confirmed suppression of dengue virus (DENV) infection and proliferation in Aedes aegypti.
https://www.frontiersin.org/articles/10.3389/fimmu.2021.640367/full

A human C-type lectin protein CLEC18A binds to glycoprotein of dengue virus, induces type-I interferon secretion, making CLEC18A one of players in innate immune responses to DENV infection (detailed glycan binding specificity of CLEC18A is not clear, but usually C-type lectins bind to high mannose or Gal/GalNAc). This study suggests a possibility that could suppress the spread of DENV infection and proliferation by using transgenic mosquitoes.

Inactivation of the new corona virus (SARS-CoV-2) by UV-C irradiation

A group from University of Milan, etc. has reported on inactivation of SARS-CoV-2 with UV-C irradiation.
https://www.nature.com/articles/s41598-021-85425-w

Authors irradiated UV-C (254nm) on V6 cells with different Multipulicity of Infection (MOI). 0.05 MOI, 5 MOI, and 1000MOI. 0.05 MOI is equivalent to the low-level contamination observed in closed environments, 5 MOI corresponds to the average concentration found in the sputum of COVID-19 infected patients, and 1000 MOI is a very large concentration, corresponding to that observed in terminally diseased COVID-19 patients. In a range from 0.05 MOI to 5 MOI, a very small dose of 4 mJ/cm2 was enough to achieve full inactivation of the virus. Even at the highest value, 1000 MOI, virus was totally inactivated with a dose of 16.9 mJ/cm2.

Longitudinal analysis of IgG levels and memory B cells following Pfizer (BNT162b2)/Moderna (mRNA-1273) vaccination

A group from University of Pennsylvania Perelman School of Medicine has reported longitudinal analysis results of IgG levels and memory B cells following Pfizer (BNT162b2)/Moderna (mRNA-1273) vaccination.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941668/

  1. Vaccination boosts antibody levels for both SARS-CoV-2 recovered people and SARS-CoV-2 inexperienced people
  2. but, no additional boosting is observed after the second vaccine dose for SARS-CoV-2 recovered people
  3. Memory B cell responses continue to improve after the second dose for SARS-CoV-2 inexperienced people
  4. All ages benefit from vaccination, but vaccine induction of memory B cells declines with age
  5. No relationship between post-vaccine IgG levels and memory B cells in SARS-CoV-2 inexperienced people
  6. Memory B cells strongly correlate with post-vaccination IgG levels in SARS-CoV2 recovered people
  7. The importance of measuring memory B cells induced by the vaccination is emphasized

So, this means that SARS-CoV-2 recovered people do not need vaccination twice, but SARS-CoV-2 inexperienced people do need vaccination twice definitely.

Monochronal Antibody Cocktails would be effective in rapidly mutating RNA viruses such as SARS-CoV-2 

A group from Fred Hutchinson Cancer Research Center, etc. has investigated the effect of genomic mutations onto two types of monochronal antibodies (LY-CoV555 and LY-CoV016) against RBD of SARS-CoV-2.
https://www.biorxiv.org/content/10.1101/2021.02.17.431683v1

It was found that LY-CoV016 is very weak for K417N mutation, and LY-CoV555 is so weak for E484K mutation. In both cases, IC50 increased more than 1,000 times with these mutations. Therefore, a strategy using antibody cocktails with different monochronal antibodies with different target epitopes would be quite effective in developing therapeutic drugs for rapidly mutating RNA viruses such as SARS-CoV-2.