Genetic Variations that Predispose People to Severe COVID-19, Cause of Acute Deadly Hepatitis in Children Likely Identified, SARS-CoV-2 Origin Still Being Investigated

There’s Science and then there’s conjecture. Where politics and science are intentionally intermingled you will find the latter.

Genetic Variations that Predispose People to Severe COVID-19

Research published today in the journal Nature identified 49 genetic variants, 16 previously unreported,  associated with critical COVID-19 infection. The team of researchers analyzed the genetics of 24,202 patients with severe cases of SARS-CoV-2 infection requiring continuous cardiorespiratory monitoring or organ support.

“Figure 2. a,b, The predicted effect of change in protein concentration (a) and gene expression (b) on the risk of critical COVID-19 is shown for proteins and genes significantly linked to critical COVID-19 by GSMR (false-discovery rate (FDR) < 0.01). The bars show 95% confidence intervals.

This research may contribute to the development of additional SARS-CoV-2 therapeutics and treatment protocols as many of the genes identified are ‘druggable’ targets, meaning a drug can possibly be developed to reduce the severity of SARS-CoV-2 infection. Interestingly, the group found no differences in gene expression between the sexes though men are known to die at a higher rate from SARS-CoV-2 than women.

In a previous publication the same group identified association between low expression of IFNAR2, or high expression of TYK2 with severe disease. A recent clinical trial demonstrated that a JAK inhibitor Baricitinib which can target TYK2 showed clinical improvement.  Baricitinib is an oral drug approved for treatment of arthritis and was granted EUA for treatment of COVID-19 in the hospital setting in the United States. This research published in Lancet validates the use of genome wide screening for identification of therapeutically relevant targets in the face of a new disease. The clinical trial can be found here: ClinicalTrials.gov (NCT04381936).

Cause of Acute Deadly Hepatitis in Children Likely Identified

Do you remember the sudden 2022 spike in cases of deadly hepatitis in children where researchers couldn’t find the cause? I do.

A massive collaboration across 19 departments in the UK led to this publication in Nature in March 2023 identifying the likely cause of these deadly infections, now identified in 35 countries with 1010 probable cases.

It turns out the causal agent is co-infection with two viruses combined with genetic pre-disposition related to the highly variable immune system genes HLA class II. The HLA-DRB1*04:01 allele combined with adeno-associated virus 2 (AAV2) and what the authors say is most likely co-infection with human adenovirus that acts as a ‘helper virus’ to support AAV2 replication.

What’s concerning is the question, what changed?

This genotype is relatively common among HLAs, it is not rare, particularly in Northern Europe. HLA-DRB1*04:01 is highly associated with autoimmune diseases such as RA, T1D, and pemphigus, and is also associated with asymptomatic SARS-CoV-2 infection.

Likewise, AAV and co-infection with a helper virus is not new. AAV viruses are considered endemic, infecting 35-80% of the population with AAV2 being the most prevalent serotype (77% of infections in some studies).

The authors do show that a wave of SARS-CoV-2 cases preceded the spike in hepatitis cases. (Figure 1, below). So, while the casual virus infection may have been identified, I personally, can’t help but wonder if we need to dig a little deeper into the etiology of this disease, especially in the context of COVID-19 induced immune system dysfunction and dysregulation.  

SARS-CoV-2 Origin Still Being Investigated  

Today, a report led by Marco Rubio was published detailing the activities of China prior to and during the initial years of the SARS-CoV-2 pandemic. I have gone through the 329 pages and below I discuss a few of the things that caught my attention.

From the report:

“To be clear, it is the aggregate picture that emerges from this report – not any particular piece of information standing as a proverbial ‘smoking gun’ – which matters most when assessing the origin question,” the report stated.

As an objective observer I can say that this would be the first known example of a lab-leaked of man-made origin if this were to be true. Is it possible? It cannot be ruled out definitively. Is it likely? Current evidence including positive samples in the Wuhan Seafood market in booths with animals that are known carriers indicate it is still unlikely.

It is known that the intelligence community has not reached a consensus on the origin of the pandemic despite having all of the same information.

Here’s the tally:

The Energy Department and the FBI support the theory that the virus accidentally emerged from the lab in China with “weak evidence”.

Four other agencies and a national intelligence panel said they believe the pandemic likely started with natural transmission from animal to human.

Two other agencies including the CIA, are undecided.

What this new report details (all 329 pages with just under 100 pages of references) are the activities of government officials, speeches, safety precaution implementation as early as July 2019, and airport drills run for both radioactive material and a novel corona virus.

Since the report failed to review prior frequency of many of these issues being addressed the fact that they were performed in 2019 without a historical context becomes meaningless. Biosafety drills and “war games” are run by countries around the world on a regular basis. Therefore it’s difficult to conclude the timing was anything more than coincidental.

The report cites a speech given by Xi Jinping in great detail. The CCP leader spoke of great conflict and difficulty ahead. This may have well been about growing US – China tensions over Taiwan.

In another area of the report they cite an article published by Dr. George Fu Gao in March, 2019 regarding the risk of genetically modified pathogens. I can assure the authors of this report this is far from the first time an article discussing the risk of genetically modified pathogens was published by a scientist.

The report continues with detailing the various activities of scientists and the Chinese government during this time. None of it a conclusive indication of a lab leak, as admitted by the authors of the report who I suggest engage in further understanding of the scientific world and scientists’ activities if they wish this snapshot in time to appear relevant (or perhaps it won’t and that’s the problem).

Here is what concerns me in the report:

First the report detailed poor laboratory conditions in the new BSL-4 facility. It is difficult to confirm all of the sources for this report. However, if true this is incredibly serious and begs international involvement and inspection of laboratory facilities operating at a BSL-4 level. I imagine something similar to the way nuclear sites are inspected.

If we do definitively confirm that the SARS-CoV-2 virus came from a laboratory (most scientists reviewing the evidence do not believe this to be true). It would be a massive blow to the global research community. The public backlash, rightfully so, would be significant. There are several BSL-4 laboratories all over the world. They operate without incident. However, this new BLS-4 laboratory was arguably cutting corners. Would all research stop? I believe that would be a mistake. Researching deadly pathogens is critical for being prepared for inevitable pandemics. Just because we stop investigating deadly viruses does not mean nature will stop creating them. We could be caught flat-footed when (not if) the next deadly virus arrives.

Many different strains of evidence support and suggest that the spread of SARS-CoV-2 was well under way before December of 2019. This report does detail some of that evidence, but there is more that it missed. For example, spike protein binding antibodies found in the blood supplies around October of 2019. As we have seen SARS-CoV-2 mutate in our population once all eyes were turned towards it’s trajectory, it is possible that a pre-Wuhan variant was in circulation and much like we’ve seen with other variant evolution a crowded Wuhan market became the jumping-off point for the next more infectious and deadly version. This however, still does not support a ‘lab leak’ theory as zoonotically (animal to human) transmitted viruses behave the same.

Finally, the report discusses bioweapons programs. Much like a nuclear arms race, bioweapons programs are both terrifying and have been supported by every developed nation for decades. This is not evidence of a laboratory leak. But, if I were asked my opinion, I’d tell the world to knock It off we have enough problems.