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

[Hutan]

From the information about the FLiRT variant above:

How long does long covid last?
Most people with Covid-19 feel better within a few days or weeks of their first symptoms and make a full recovery within 12 weeks, the NHS states.

Effects can last longer, however, with longer symptoms typically including fatigue, shortness of breath, dizziness and joint ache or pins and needles.The length someone typically suffers with long covid is not known due to the recency of the virus. According to News Medical Life Sciences, however, the symptoms do improve after two years.

So, that's alright then...

 

[Trish]

According to News Medical Life Sciences, however, the symptoms do improve after two years.

From the conclusion of the linked article:

The findings suggested that while both symptoms showed improvements over a span of two years in approximately 50% of the patients, specific risk factors such as depressive symptoms and headache predicted non-recovery from fatigue in the long term. Old age and male sex were two of the risk factors indicating non-recovery from cognitive deficits in long-COVID patients.

 

[Ash]

From the information about the FLiRT variant above:

So, that's alright then...

+…?

 

[rvallee]

Why the new FLiRT group of variants is expected to bring a new wave of Covid (msn.com)

 

[rvallee]

From the information about the FLiRT variant above:

So, that's alright then...

What a cheap cop out, to use the "novelty" of the virus but to use 2 years, as a point where symptoms improve in some but not all, when it's already been 4. Which of course ignores the fact that this problem has been known for decades.

Medicine is really putting out a masterclass in how to destroy the credibility of experts. Of all experts, sadly. This is explicitly using professional credibility to lie to and mislead people, with clear intent and purpose.

 

[SNT Gatchaman]

Preprint showing hydroxycholoroquine may have been a bad idea, upregulating endothelial ACE2 expression.

Chloroquine Up-regulates Expression of SARS-CoV-2 receptor Angiotensin Converting Enzyme-2 in Endothelial Cells
Hien C Nguyen; Shuhan Bu; Lynn Wang; Aman Singh; Krishna K Singh

BACKGROUND AND PURPOSE
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) posed a serious threat to global public health. Hydroxychloroquine (HCQ), which is a derivative of Chloroquine (CQ), was a WHO-recommended drug to treat COVID-19 with mixed effects. The purpose of the present study is to evaluate the plausible mechanisms of HCQ actions behind its observed mixed effect.

KEY RESULTS
We demonstrate that CQ-treatment significantly up-regulates mesenchymal markers and SARS-CoV-2 receptor ACE2 in cultured endothelial cells.

CONCLUSIONS & IMPLICATIONS
The detrimental effect of HCQ in seriously ill COVID-19 patients might be due to CQ-induced increased expression of endothelial ACE2 exacerbating the severity of SARS-CoV-2 infection. Our study warrants further investigation in animal models and humans and caution while prescribing HCQ to patients with an impaired renin-angiotensin-aldosterone system, such as in hypertension, cardiovascular diseases, or chronic kidney disease; particularly with ACE-inhibitors or statin therapy.


Link | PDF (Preprint: BioRxiv) [Open Access]

 

[SNT Gatchaman]

Preprint showing hydroxycholoroquine may have been a bad idea

Sabine Hossenfender — Unapproved Trial for Discredited COVID Cure: Scandal In France

"In 2020, French physician Didier Raoult claimed that hydroxychloroquine was a cure for Covid-19. The results could later not be reproduced, but tens of thousands of people died because they did not receive or not seek treatment that might actually have helped them. Unbelievable as it sounds, the story of his unethical practices continues to this day. I have the summary."

 

[Wits_End]

Mainly USA:

https://www.huffingtonpost.co.uk/entry/covid-summer-2024-surge-symptoms_l_6679820de4b0d2f6354efe63

"The FLiRT variants are offshoots of JN.1, which was the dominant variant in the U.S. this past winter.

This family of variants appears to be very contagious, thanks to mutations in the spike protein that may improve the virus’s ability to bind to human cells. “When we look at their molecular profile, some of those mutations potentially could allow the [virus] to escape from previous immunity,” Hopkins explained."

 

[wastwater]

Covid-19: First coronavirus was described in The BMJ in 1965

The history of coronaviruses since 1931
https://www.bmj.com/content/369/bmj.m1547/rr-2

I also wondered if coronavirus have been modified for biological warfare if there maybe a mk1 and mk2 or just natural evolution

What happens if you are modified with a coronavirus (like Cytomegalovirus causing birth defects)

Does infection with coronavirus activate EBV to do endothelial damage
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292739/

 

[Amw66]

Could be a significant evolutionary mechanism .
Reinstatement of previous deletions , not possible with stepwise evolution , but via a previous lineage without deleted variations .
Does this happen in any other virus ?

https://twitter.com/user/status/1736526826179092781


The ∆69-70 pendulum is in the midst of yet another swing.
What makes the alternation from ∆69-70 to S:H69+ S:V70 even more remarkable is that deletions are one-way mutations. They essentially cannot be reversed. There has never been an insertion at S:69-70 in SARS-CoV-2. 1/5

So how, after repeated deletion of S:69-70, have S:H69 + V70 been restored? This cannot happen via stepwise evolution/antigenic drift.

But it can if a new variant derives from an old, vanished lineage that's never had ∆69-70 & has spent months evolving in a single person. 2/5

There has been great work on deletions in the NTD region of spike by @GuptaR_lab, @EnyaQing, @GroveLab, & others, some of which I tried to describe in the thread below.
But a precise explanation for the ∆69-70 pendulum remains elusive. 3/5
x.com/LongDesertTrai…. Thread link reference https://twitter.com/user/status/1569025039109873668


Is SARS-CoV-2 the only virus in which successive dominant variants derive from long-term intrahost evolution in individual hosts?
It seems so, but with better genetic surveillance, perhaps we'll find others—Norovirus is a candidate. Maybe noro guru @Chris3Ruis can elaborate? 4/5

I wrote the thread below in April 2022, incorporating some history of science, in an attempt to decipher if the ∆69-70 pendulum was a real phenomenon that would continue or, like so many other things, just an odd, meaningless coincidence. 5/5
x.com/LongDesertTrai…

Related thread
https://twitter.com/user/status/1722352486638354663

 

[SNT Gatchaman]

Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations
Jingyi Liu; Yuanling Yu; Fanchong Jian; Sijie Yang; Weiliang Song; Peng Wang; Lingling Yu; Fei Shao; Yunlong Cao

P.3, a subvariant of JN.1, has rapidly emerged as the dominant strain of SARS-CoV-2 in several countries, and has been designated as a Variant Under Monitoring. Previous studies indicate that the unique Q493E substitution in KP.3 Spike glycoprotein enhances its receptor ACE2-binding affinity and immune evasion, enabling it to outcompete KP.2.1–6 Notably, KP.3.1.1, which only carries one additional S31 deletion compared to KP.3, has surpassed KP.3 to become the new dominant strain globally (figure A; appendix p 4).7 Meanwhile, XEC, a recombinant variant of KS.1.1 and KP.3.3, shows strong potential to become the next dominant strain, rapidly expanding across Europe and North America. Compared with KP.3, XEC has only two additional spike mutations, F59S and T22N (appendix p 4). Both S31del and T22N introduce potential glycosylation on the N-terminal domain. Consequently, there is an imperative need to characterise the antigenicity and infectivity of KP.3.1.1 and XEC.

Link | PDF (The Lancet Infectious Diseases) [Open Access]

 

[boolybooly]

Reinstatement of previous deletions , not possible with stepwise evolution , but via a previous lineage without deleted variations .
Does this happen in any other virus ?

Probably.

"Recombination in Coronaviruses, with a Focus on SARS-CoV-2" Focosi & Maggi
https://www.mdpi.com/1999-4915/14/6/1239

Recombination represents a major contributor to RNA virus evolution [1] together with re-assortment (which exclusively operates in RNA viruses with segmented genomes). Recombination can occur both in segmented [2,3] and non-segmented RNA viruses [4,5,6,7] and avoids an accumulation of irreversible deleterious mutations typical of asexual reproduction (so called “Muller’s ratchet” [8]). “Donor” and “acceptor” are conventional terms used to refer to the strain represented in a greater and lesser amount, respectively. Recombination within different sublineages of the same virus invariably requires co-circulation and co-infection of the same host.

Speaking subjectively as a zoologist it seems inevitable really. If viruses persist in carriers with asymptomatic infection, who we know exist by the epidemiology of COVID spread, possibly in those who have long covid though there has been a failure to find active virus in long covid patients in the literature which may be due to a failure to identify refugia but it implies their immune system is active and they are not shedding viable virus. So it is a possibility that replicating strains of covid can coinfect the same cells in carriers.

There are likely to be a great many such carrier individuals aka "Typhoid Marys", not a few, as viral carriage is likely to be an evolutionarily advantageous strategy as with grey squirrels, the strategy being to pass the virus on so that the individual concerned is not at a disadvantage and everyone else has the same infection to contend with. Grey squirrels have evolved to use the squirrelpox virus as a biological weapon in their competition with the red squirrel. This kind of evolutionary pressure could also well explain the evolution of sneezing which if you think about it is the perfect way to spread respiratory viruses and we all do that.

In the intracellular environment containing coinfections by different variants which the carrier strategy probably creates, crossover events might occur, where one RNA strand is joined with another, most of which would not be viable but these would be naturally selected for viability and the viable recombinants would emerge from infected cells to replicate within the individual and then spread to others.

 

[forestglip]

Science: Infamous paper that popularized unproven COVID-19 treatment finally retracted
By Cathleen O’Grady

A 2020 paper that sparked widespread enthusiasm for hydroxychloroquine as a COVID-19 treatment was retracted today, following years of campaigning by scientists who alleged the research contained major scientific flaws and may have breached ethics regulations. The paper was pulled because of ethical concerns and methodological problems, according to a retraction notice.

But scientists immediately raised concerns about the paper, noting the sample size of only 36 patients and the unusually short peer-review time: The paper was submitted on 16 March 2020 and published 4 days later. On 24 March, scientific integrity consultant Elisabeth Bik noted on her blog that six patients who were treated with hydroxychloroquine had been dropped from the study—one of whom had died, and three of whom had transferred to intensive care—which potentially skewed the results in the drug’s favor. Larger, more rigorous trials carried out later in 2020 showed hydroxychloroquine did not benefit COVID-19 patients.

Critics of Raoult’s paper have pointed out more damning problems since. In an August 2023 letter published in Therapies, Bik and colleagues noted the cutoff for classifying a polymerase chain reaction test as positive was different in the treatment and control groups. The letter also raised questions about whether the study had received proper ethical approval, and noted an editorial conflict of interest: IJAA’s editor-in-chief at the time, Jean-Marc Rolain, was also one of the authors. (A statement saying he had not been involved in peer review was later added to the paper.) The letter called for the paper to be retracted.

To date, 32 papers published by IHU authors have been retracted, 28 of them co-authored by Raoult, and 243 have expressions of concern.

Link

 

[rvallee]

It's kind of funny reading the reasons for the retraction and how they all super standard problems in psychobehavioral studies that form the entire psychosomatic evidence base, most of which is even worse. It's well-known that those studies are worthless based on their methodology and design. And still it takes such a high profile example 4 years to get to a retraction.

 

[Yann04]

It's kind of funny reading the reasons for the retraction and how they all super standard problems in psychobehavioral studies that form the entire psychosomatic evidence base, most of which is even worse. It's well-known that those studies are worthless based on their methodology and design. And still it takes such a high profile example 4 years to get to a retraction.

Yeah. At this point I’m starting to wonder if peer review is more harmful than anything.

It doesn’t seem to do much quality control wise, but it seems to be a way of enforcing the standard view of academics in the field and rejecting questionings of the norm.

 

[rvallee]

Yeah. At this point I’m starting to wonder if peer review is more harmful than anything.

It doesn’t seem to do much quality control wise, but it seems to be a way of enforcing the standard view of academics in the field and rejecting questionings of the norm.

Yeah I think at this point peer pressure is a more accurate term. Not much reviewing going on, certainly not based on any actual standards.

 

[SNT Gatchaman]

Previously (2020/1) we had a lot of "children don't get COVID" which morphed into "children aren't severely affected" and Children are unlikely to be the main drivers of the COVID-19 pandemic – A systematic review (2020, Acta Paediatrica)

All those confident statements turned out to be very not true (along with "not airborne", "one and done", "no lasting effects" etc etc). Here's a Belgian study.

Assessing the role of children in the COVID-19 pandemic in Belgium using perturbation analysis (2025)
Angeli, Leonardo; Caetano, Constantino Pereira; Franco, Nicolas; Coletti, Pietro; Faes, Christel; Molenberghs, Geert; Beutels, Philippe; Abrams, Steven; Willem, Lander; Hens, Niel

Understanding the evolving role of different age groups in virus transmission is essential for effective pandemic management.

We investigated SARS-CoV-2 transmission in Belgium from November 2020 to February 2022, focusing on age-specific patterns. Using a next generation matrix approach integrating social contact data and simulating population susceptibility evolution, we performed a longitudinal perturbation analysis of the effective reproduction number to unravel age-specific transmission dynamics.

From November to December 2020, adults in the [18, 60) age group were the main transmission drivers, while children contributed marginally. This pattern shifted between January and March 2021, when in-person education resumed, and the Alpha variant emerged: children aged under 12 years old were crucial in transmission. Stringent social distancing measures in March 2021 helped diminish the noticeable contribution of the [18, 30) age group. By June 2021, as the Delta variant became the predominant strain, adults aged [18, 40) years emerged as main contributors to transmission, with a resurgence in children’s contribution during September-October 2021.

This study highlights the effectiveness of our methodology in identifying age-specific transmission patterns.

Link | PDF (Nature Communications) [Open Access]