SARS-CoV-2 Coronavirus (COVID-19)

Very interesting! As I read it, the critical parts of the success stories are:

Testing of all at-risk incoming travelers even before cases start to occur (not true of US)
Mass country-wide testing done quickly at multiple labs (not done in US)
Contact tracing and quarantine of all contacts (not done in US)
Surplus hospital bed capacity for surge in demand (not true of US)

 

Found this interesting article.
CT scans might offer a more accurate way to diagnose Covid-19 - STAT

According to the article, current RT-PCR for COVID-19 testing is missing up to 30% of true positives. Using CT scan is said to be more accurate. This is amazing considering that most PCR platform in use in the US is very robust and quite sensitive. Most system can detect presence of virus down to 10 viral genome per 40ul of sample they run. As the article suggests, the high rate of false negative in current swab testing is not due to the sensitivity of the PCR but due to procedural error of nasopharyngeal swab sampling. I would think if FDA (or maybe CDC?) protocol allows sampling of saliva instead of swab, this should all be corrected very easily.

As for the use of CT scans for diagnosis, it would be very costly and far more time consuming than PCR as it is not amenable to automation like PCR testing. I also wonder if the CT scan would reveal asymptomatic patients infected by virus, which PCR testing can easily detect.

 

Testing by dogs?

 

I published this quiz about a week ago:

POP QUIZ

1. What is the role of the polybasic site in the spike protein in CoV-2 transmission? (A. The redundant proteins make it harder to make a universal antigen. It is the anti-antigen protector so there won't be a simple vaccine.)
2. What are the pathways involved in CoV-induced membrane remodeling, and how do RTCs temporally and functionally coordinate various stages of the viral lifecycle? (A. The 'noisy' or 'imprecise' virus replication means in addition to hardcore replicants there are large numbers of experimental variants. Most fail but if one of them finds an internal cell biology block, there is a chance one or two of the imprecise replicants can rapidly adapt and carry on the virus family.)
3. What are the biochemical activities and roles of the various proteins that form the replication-transcription complex, and how do they coordinate genome replication vs. transcription? (A. Virus replication is not 100% accurate but just enough to reproduce the original. However the inaccurate, often fatal variants, may include ones that can reproduce even in the presence of the known, cell molecular processes.)
4. How do CoVs maintain such a large genome and still have sufficient mutation rates for adaptation and trans-species movement? (A. Volume, volume, volume! The virus is so small that a single cell can easily make orders of magnitude more replicants.)
5. What are the functions of the CoV-2 accessory proteins, and how do they impact the in vivo growth and virulence of the virus? (A. Like having more than one engine on planes with unreliable engines, this increases how the virus can remain robust. The risk of a 'magic bullet' has been reduced.)
6. Will CoV-2 infected individuals (or vaccines) mount protective long-term immune responses? (A. No! It needs a wider response including more sensitive patient detection and contact tracing. Contact tracing is the "hand of God" to a virus.)

EXTRA CREDIT:
What is unique about the interferon response that makes CoV2 lethal? (A. Interferon is specific to the virus being defended against. So the imprecise virus replication means no one interferon can be the 'magic bullet.')

Ok, so how did I do?

Bob Wilson

 

Some breaking news:

Futures surge as Gilead coronavirus drug reportedly shows effectiveness

 

There is even a simpler method, Ultrasound:

 

Some surprising news:

China virus epicentre Wuhan raises death toll 50% | AFP.com

 

Interesting. But I still think lung CT or Ultrasound can diagnose COVID-19 only if the infected person has respiratory symptoms. I would think they miss people with milder non-respiratory symptom or asymptomatic infected indivisuals.

 

I think they are more for differentiating COVID-19 from flu and other types of pneumonia.

 

Yes, I think currently it is being used for the patients with "pneumonia" like symptom that are negative with swab test. But the article I linked above is arguing that due to lower rate of "missing" true positives, this very cumbersome CT scan test may be needed to be used for large population confirmation testing for the SARS-Cov2 infection before opening up the country. I just don't see that is plausible.

 

Thanks!

This link provides more details: Gilead data suggests coronavirus patients are responding to treatment

NOTE: Preliminary treatment reports are important but large scale, studies are needed too.

Bob Wilson

 

As I look at the microbiology, especially the protein spikes, I'm beginning to suspect coronavirus has multiple attack points, not just the lung. In effect, the noisy RNA replication can make derivatives that can attack other parts.

Bob Wilson

 

From the genomic sequence analyses, the SARS-Cov-2 is known to use the receptor protein ACE2 on the cell surface to gain the entrance to the cell which is shared with very similar SARS-Cov (the virus responsible for the 2002-2003 SARS pandemic).
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor - ScienceDirect

As you can see from the link below, ACE2 receptor is expressed in many organs in human body beside lung, including endocrine organs, GI organs, liver, kidney, muscle, reproductive organs, etc. Any cells expressing ACE2 receptor can be targeted by SARS-Cov-2.

Tissue expression of ACE2 - Summary - The Human Protein Atlas

 

Stanford study out for pre-print:

...Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARSCoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer’s data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both.

Results The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50- 85-fold more than the number of confirmed cases.

Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections....

...We can use our prevalence estimates to approximate the infection fatality rate from COVID-19 in Santa Clara County. As of April 10, 2020, 50 people have died of COVID-19 in the County, with an average increase of 6% daily in the number of deaths. If our estimates of 48,000-81,000 infections represent the cumulative total on April 1, and we project deaths to April 22 (a 3 week lag from time of infection to death22), we estimate about 100 deaths in the county. A hundred deaths out of 48,000-81,000 infections corresponds to an infection fatality rate of 0.12-0.2%. If antibodies take longer than 3 days to appear, if the average duration from case identification to death is less than 3 weeks, or if the epidemic wave has peaked and growth in deaths is less than 6% daily, then the infection fatality rate would be lower. These straightforward estimations of infection fatality rate fail to account for age structure and changing treatment approaches to COVID-19. Nevertheless, our prevalence estimates can be used to update existing fatality rates given the large upwards revision of under-ascertainment....

https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1.full.pdf

 

The woman who discovered the first coronavirus - BBC News

 

The AlCovid-19 Study - brainandbehaviourlab

 

High Levels Of SARS-CoV-2 Discovered In Urban Wastewater System