The biology of coronavirus COVID-19 - including research and treatments

Cats can infect each other with coronavirus, Chinese study finds

https://www.theguardian.com/world/2...ch-other-with-coronavirus-chinese-study-finds

 

Coronavirus: Plasma therapy has begun in 5 US patients. Will it work?

https://eu.usatoday.com/story/news/...apy-5-us-patients-covid-19-donors/5090946002/

 

https://twitter.com/user/status/1245810499297652749

 

People are talking about recombining ACE2 with the FC region (antibody attachment site) to block the virus spikes and mark it for disposal.

https://f1000research.com/articles/9-72

https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2.full.pdf

Not sure what this is but it looks like its on sale for lab testing already!
https://www.sinobiological.com/recombinant-proteins/human-ace2-10108-h02h

Which looks interesting but having wrestled with trying to understand Antibody Dependant Enhancement of infection, I cant help wondering if it would carry any risks.

https://en.wikipedia.org/wiki/Antibody-dependent_enhancement

 

No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection
https://www.sciencedirect.com/science/article/pii/S0399077X20300858

Moderator note:
For more discussion of hydroxychloroquine and chloroquine, see this thread
Chloroquine and Hydroxychloroquine as treatments for Covid-19

 

Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2
https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdf

 

"BCG (TB) vaccine might protect against Covid19"

I didn't realise they'd stopped this in the UK.

But tuberculosis is bacterial, or doesn't that make any difference?
@Jonathan Edwards

eta:
https://www.reuters.com/article/us-...-help-fight-the-new-coronavirus-idUSKBN21K372

 

The tubercle bacterium has a particularly potent innate immune stimulant in it that became the central ingredient what was called Freund's adjuvant. It boosts reactivity to any vaccine given. Whether it would boost immunity to a clever virus or not is speculative but it might. The down side of the immune stimulant effect of TB is that it is probably part of the way the bacterium tricks the host into keeping it alive - by getting eaten by macrophages in which it then lives.

BCG is a benign variant of TB that can live locally in the host for a period of days and produce a local infection that is then controlled. I think the adjuvant effect would be fairly slow to take hold - over many days, which would be of little benefit in someone already very ill but might be relevant to people in the early mild phase seen in some Covid19 cases. BCG is instilled into the bladder to stimulate a local immune response that can help destroy bladder cancers.

 

Article about this in today's Irish Times.

Tuberculosis vaccine ‘potential game-changer’ in Covid-19 fight (via @IrishTimes)


https://www.irishtimes.com/news/hea...tial-game-changer-in-covid-19-fight-1.4220383

 

Vaccination in the past I think would be irrelevant. The helpful action of BCG would be only at the time of giving.

 

https://twitter.com/user/status/1246178651944693760

 

I hesitate to ask but I wonder if any of the 2215 members of the forum think they have had Covid19? nd what was it like? The only people I know so far who have had it are people who visit hospitals regularly.

This post has been copied and responses moved to this thread in the members only area.

 

It happened that I just came across this interesting review (already)

The neuroinvasive potential of SARS-cov-2 may play a role in the respiratory failure ...

abstract

Maybe it sheds even some light on ME/CFS?

 

Interesting article - linking BCG vaccination to reduced prevalence of COVID19

https://www.irishtimes.com/news/hea...-changer-in-covid-19-fight-1.4220383?mode=amp

 

There are many other uncontrolled factors, I wouldn't get too excited about this. It may even be a reporting bias, namely the non-BCG countries are reporting infection rates that are more accurate. There is a clear geographical bias between countries with current BCG vaccination policies and not: http://www.bcgatlas.org/ (on the map)

There is no reactivity between antibodies towards BCG and coronavirus.

 

News article in the San Jose Mercury news on one of the first community prevalence studies in the US run by Stanford University with antibody sampling of 2500 volunteers.

Coronavirus: New Stanford research reveals if you’ve been exposed
https://www.mercurynews.com/2020/04...nford-research-reveals-if-youve-been-exposed/

This snippet in the news article about whether antibodies provide protection was concerning

 

https://www.sciencedirect.com/science/article/pii/S0166354220302011

The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

I used it in animals but I prefer levamisole.

 

omg, a Spanish biologist answering questions on COVID 19:

 

Got something from ProMED mail that you all might find interesting.

Microneedle array delivered recombinant coronavirus vaccines
Date: Thu 2 Apr 2020

(Apologies for the length, but when about 20 years ago I asked for permission to re-post some of their mails they wanted the whole mail sending. Probably a good idea anyway, as means anyone looking at it can find sources and previous sources.)

============>>>

[5] Microneedle array delivered recombinant coronavirus vaccines
Date: Thu 2 Apr 2020
Source: The Lancet [edited]
<https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30118-3/fulltext>


ref: Kim E, Erdos G, Huang S, et al. Microneedle array-delivered
recombinant coronavirus vaccines: immunogenicity and rapid
translational development. EBioMedicine. 2 Apr 2020. doi:
<https://doi.org/10.1016/j.ebiom.2020.102743>.
--------------------------------------------------------------------------------
Abstract
---------
Background
Coronaviruses pose a serious threat to global health as evidenced by
severe acute respiratory syndrome (SARS), Middle East respiratory
syndrome (MERS), and COVID-19. SARS coronavirus (SARS-CoV), MERS
coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed
2019-nCoV, and now officially named SARS-CoV-2, are the causative
agents of the SARS, MERS, and COVID-19 disease outbreaks,
respectively. Safe vaccines that rapidly induce potent and
long-lasting virus-specific immune responses against these infectious
agents are urgently needed. The coronavirus spike (S) protein, a
characteristic structural component of the viral envelope, is
considered a key target for vaccines for the prevention of coronavirus
infection.

Methods
We 1st generated codon-optimized MERS-S1 subunit vaccines fused with a
foldon trimerization domain to mimic the native viral structure. In
variant constructs, we engineered immune stimulants (RS09 or
flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric
design. We comprehensively tested the pre-clinical immunogenicity of
MERS-CoV vaccines in mice when delivered subcutaneously by traditional
needle injection, or intracutaneously by dissolving microneedle arrays
(MNAs) by evaluating virus-specific IgG antibodies in the serum of
vaccinated mice by ELISA and using virus neutralization assays. Driven
by the urgent need for COVID-19 vaccines, we utilized this strategy to
rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their
pre-clinical immunogenicity in vivo by exploiting our substantial
experience with MNA MERS-CoV vaccines.

Findings
Here we describe the development of MNA-delivered MERS-CoV vaccines
and their pre-clinical immunogenicity. Specifically, MNA-delivered
MERS-S1 subunit vaccines elicited strong and long-lasting
antigen-specific antibody responses. Building on our ongoing efforts
to develop MERS-CoV vaccines, promising immunogenicity of
MNA-delivered MERS-CoV vaccines, and our experience with MNA
fabrication and delivery, including clinical trials, we rapidly
designed and produced clinically translatable MNA SARS-CoV-2 subunit
vaccines within 4 weeks of the identification of the SARS-CoV-2 S1
sequence. Most importantly, these MNA-delivered SARS-CoV-2 S1 subunit
vaccines elicited potent antigen-specific antibody responses that were
evident beginning 2 weeks after immunization.

Interpretation
MNA delivery of coronaviruses-S1 subunit vaccines is a promising
immunization strategy against coronavirus infection. Progressive
scientific and technological efforts enable quicker responses to
emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit
vaccines enabled us to rapidly design and produce MNA SARS-CoV-2
subunit vaccines capable of inducing potent virus-specific antibody
responses. Collectively, our results support the clinical development
of MNA-delivered recombinant protein subunit vaccines against SARS,
MERS, COVID-19, and other emerging infectious diseases.

--
communicated by:
ProMED-mail
<promed@promedmail.org>

[Microneedle arrays (MN) are minimally invasive devices that
painlessly bypass the skin's stratum corneum, which is the principal
barrier to topically applied drugs. MN (50-900 micrometre in height,
up to 2000 MN per square centimetre) have been extensively
investigated in recent years as a means to enhance transdermal drug
and vaccine delivery.
(<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627464/>)

As mentioned in the report above, the researchers used a new approach
to deliver the drug, called a microneedle array, to increase potency.
This array is a fingertip-sized patch of 400 tiny needles that
delivers the SARS-CoV-2 S protein pieces into the skin, where the
immune reaction is strongest. The patch is applied similarly to a
plaster, and then the needles, made entirely of sugar and the protein
pieces, dissolve into the skin. Furthermore, according to the vaccine
developers, the system is highly scalable. The protein pieces are
manufactured by a "cell factory" -- multiple layers of cultured cells
engineered to express the SARS-CoV-2 S protein -- that can be stacked
further to multiply yield. Purifying the protein can be conducted at
industrial scale. Mass-producing the microneedle array involves
spinning down the protein-sugar mixture into a mould using a
centrifuge. Once manufactured, the vaccine can sit at room temperature
until it is needed, eliminating the need for refrigeration during
transport or storage.
(<https://www.europeanpharmaceuticalr...eveloped-to-deliver-covid-19-vaccine-to-mice/>)

This sounds extremely promising. The use of MN-mediated vaccine
delivery for SARS-CoV-2 and other emerging pathogens will hold immense
potential for expanding access to vaccines, particularly to access
populations in developing countries. - Mod.UBA]

[See Also:
COVID-19 update (79): research update
http://promedmail.org/post/20200404.7182653
COVID-19 update (78): countries with high local transmission
http://promedmail.org/post/20200404.7182833
COVID-19 update (77): global, polio vacc on hold, new countries, WHO
http://promedmail.org/post/20200404.7182744
COVID-19 update (76): China (HU) animal, cat, owned, stray,
seropositive http://promedmail.org/post/20200403.7179946
COVID-19 update (75): China (Hong Kong) cat, OIE
http://promedmail.org/post/20200403.7179945
COVID-19 update (74): countries with high local transmission
http://promedmail.org/post/20200403.7178356
COVID-19 update (73): global, cruise ships, new countries, WHO
http://promedmail.org/post/20200403.7178355
COVID-19 update (72): countries with high local transmission
http://promedmail.org/post/20200402.7174839
COVID-19 update (71): global, Taiwan, new countries, WHO
http://promedmail.org/post/20200402.7174769
COVID-19 update (70): China (Hong Kong) cat, pets & stock
http://promedmail.org/post/20200402.7173286
COVID-19 update (60): global, cruise ships, lessons learned, WHO
http://promedmail.org/post/20200329.7156949
COVID-19 update (50): China (Hong Kong) dog, 2nd case PCR positive,
OIE http://promedmail.org/post/20200323.7129951
COVID-19 update (40): global, Europe epicenter, lockdown, phone
tracking, WHO http://promedmail.org/post/20200315.7092618
COVID-19 update (30): China (Hong Kong) dog, susp, serology pending
http://promedmail.org/post/20200306.7057595
COVID-19 update (20): China, global, Italy, Iran, Nigeria, imported
cases, WHO http://promedmail.org/post/20200228.7032761
COVID-19 update (10): China, global, Iran, WHO
http://promedmail.org/post/20200219.7005749
COVID-19 update (01): China, global, EVZD, reporting criteria, WHO
http://promedmail.org/post/20200213.6984084
Novel coronavirus (42): China, global, COVID-19, SARS-CoV-2, WHO
http://promedmail.org/post/20200211.6979942
Novel coronavirus (41): China, global, clinical pics, asymptomatic
trans., WHO http://promedmail.org/post/20200210.6976117
Novel coronavirus (40): animal reservoir, pangolin poss intermediate
host, RFI http://promedmail.org/post/20200210.6972104
Novel coronavirus (30): updates, China, Viet Nam, research
http://promedmail.org/post/20200202.6945658
Novel coronavirus (20): China, wildlife trade ban
http://promedmail.org/post/20200127.6922060
Novel coronavirus (10): China (HU, GD, BJ)
http://promedmail.org/post/20200119.6898567
Novel coronavirus (01): China (HU) WHO, phylogenetic tree
http://promedmail.org/post/20200112.6885385
Undiagnosed pneumonia - China (HU) (10): genome available, Hong Kong
surveill. http://promedmail.org/post/20200111.6883998
Undiagnosed pneumonia - China (01): (HU) wildlife sales, market
closed, RFI http://promedmail.org/post/20200102.6866757
2019
---
Undiagnosed pneumonia - China (HU): RFI
http://promedmail.org/post/20191230.6864153]
.................................................uba/tw/sh

------------------------------

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End of ProMED Digest, Vol 94, Issue 13
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