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Posts Tagged ‘Science progress’


Where are we in the pandemic?

The bottom line here is that anyone making the statement ‘coming out of the Covid environment’ has not kept up with the data, which demonstrate the following:

1. Transmission is ~ 98% via airborne aerosols, known since March 2020 and firmly established by initial rules on masking and regions where this is maintained.

2. The pandemic is unabated. Cases remain high, with several waves a year. This to the extent that hospital beds fill up every wave, world-wide health care workers are burning out due to overwork and waiting lists are getting so long that the best option is becoming the avoidance of ill health.

3. Deaths are lower due to vaccines, but SARS-CoV-2 is an adept immune escapologist

4. Long Covid is a growing socio-economic problem, a consequence is the loss of members of an organisation’s workforce.

5. Viral persistence is measurable 15 months after recovery, and among the targets is bone marrow and the immune system.

6. There is no cure and no efficacious treatment, and this is true  for acute infection (when you have overt symptoms for ~ 10 days), viral persistence (months/years, see below) and LongCovid (see below). This is in contrast to HIV.

The consequences of the above are that organisations need to:

A. Explicitly state that masks are expected to preserve the health of yourself and of your co-workers and provide masks to the workforce.

B. Explicitly provide details on ventilation of rooms occupied by the workforce and/or install HEPA filters in all such rooms.

C. Expect those with even partial symptoms have a clear LFTs before returning to work.

D. Provide updates on the status of current variants, how much we don’t know and the extent to which Public Health surveillance is reliable.

Anything else is a gross dereliction of duty on the part of an organisation’s management.

Below I take each of the above statements and provide the evidence, including links. If any reader from my workplace, the University of Liverpool can come up with an argument based on evidence why we should not take all possible measures against transmission, then I will accept that the University does not need to take such measures. Until then, not doing so remains a gross dereliction of duty.

Transmission

Transmission is ~98% by airborne aerosols. Aerosols DO NOT drop to the ground, they remain airborne, and the only protection is to reduce their concentration. This is achieved by two complementary routes:

Masks to reduce the amount of aerosols put into the air by an infected person;

Ventilation and filtration to ensure rapid dilution.

Some resources and comments on these

A nice article in PNAS on how secondary physical measures work, which should be on the desk of every organisations’ Health and Safety Office.

A very simple message from JAMA in an article on this subject

“Because no single approach is 100% effective in preventing COVID-19, prevention measures work best when layered, including vaccination and nonpharmacologic interventions that reduce inhalation of infectious particles.”

The same article makes further excellent points. One on the long-term implications for building design

“Reducing contaminants in shared air by improving air handling systems in buildings is an attractive, broadly effective structural measure that does not require repeated individual actions.”

There is a nice Sci-Comm piece here.

The evidence on the efficacy of the different layers of is that you are safer in a small room with an unvaccinated person, both wearing a FFP2/N95 masks, than in the same room, both vaccinated but  without masks.

We should of course as far as possible have all measures in place.

Pandemic is unabated

Data acquisition is being dismantled, so it is essential to employ critical faculties. The testing programme is no longer functional, since you cannot report the results of tests purchased privately. Moreover, the excellent ONS survey will soon be limited, so we will have even less information on the number infected later in the year, and the only proxy will then be NHS data on admissions and bed occupancy.

For the record the ONS survey data are here and for the week ending 29 June 2022 for England the estimated number of people testing positive for COVID-19 was 2,154,000 (95% credible interval: 2,062,600 to 2,247,100), equating to 3.95% of the population, or around 1 in 25 people.

There are very useful analyses of these data, which I recommend, e.g., @TravellingTabby on Twitter who maintains an excellent data web page from the ONS data

The idea that the virus is attenuating is WRONG. As usually small numbers, large effect sizes, when we go to a good sized study (130 k patients) there is no evidence that Omicron is milder

Deaths are lower

The estimate from WHO is that vaccines have avoided 20 M deaths. However, excess deaths over historical average still substantial. The problem is that the efficacy of the vaccines is good, but not nearly good enough. This is compounded by giving the virus a free reign so that natural selection can operate at extremely high throughput. The result is a virus that was already good at immune escape is now a master. Some data in the links below.

The Tweetorial from Deepti Gurdasani covers a recent Science paper that demonstrates immune escape and that T-cell immunity to Omicron is poor at best

The paper is here.

Long Covid

This occurs in a significant number of people after they recover from acute infection. The risk only reduced a little by vaccination according to this large study of 33 k people infected after vaccination with over 13 M controls!

A key take home message from this paper is:

Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI. 

Importantly, the risk of LongCovid increases with each infection.

The ONS (UK) data form early April 2022 indicate 1.7 million people with LongCovid in the UK (2.7% of the population), and it also affects the young…:

“40,000 aged 2-11 (confidence intervals 32K-48K) 59,000 aged 12-16 (confidence intervals 52K-66K) That’s a total of 99,000 children “

For those aged 17-24, that’s 89,000 (CI 77K-102K)

For those with an illness duration of at least A YEAR: 14,000 aged 2-11 (confidence intervals 9K-19K) 17,000 aged 12-16 (confidence intervals 13K-20K) That’s a total of 31,000 children. For those aged 17-24, that’s 45,000 (CI 36K-54K).

Unfortunately, those affected cannot pursue their usual lives and work, studies, hobbies, etc., are largely or completely suspended.

There is good evidence that micro clots are part of the problem and it seems likely that viral persistence in our organs may also contribute.

Viral persistence

Data from autopsies demonstrate viral persistence in organs in even moderate cases (so no hospitalisation) up to 15 months post infection. These data are likely to get worse, rather than better as we progress into the pandemic and we acquire more time-dependent data.

There is no cure and vaccines are an aid, but not a solution

The drugs we have are merely re-purposing existing ones, and their efficacy is modest, at best. It will be some time, 5 to 10 years  perhaps, before we have drugs that specifically target SARS-CoV-2 functions such as its polyprotein protease. There is good evidence for microclots playing a role in LongCovid, but we haven’t yet got a clinical trial running with preregistered outcomes etc. – so far we have case reports only.

Current vaccines are losing efficacy against variants more adept at immune escape, an entirely predictable outcome given near zero measures to reduce transmission, so the virus has had an evolutionary field day exploring host-pathogen interactions, to our detriment of course.

The future without measures beyond vaccination

Attrition of the workforce, most pronounced in those exposed to large numbers of humans in small spaces, such as healthcare and education.

Attrition of the student population able to undertake studies.

The outcome is that society is not sustainable, in the same way that Medieval societies were not sustainable in the face of population loss due to the Plague. One only has to consider the complex chain of skills that underpin basic everyday aspects of life:

The mobile phone, needs cutting edge sills in materials, chips, telecommunications networks, GPS satellites, electricity production, and of course software in all elements of the chain. 

Take out 10% of the workforce and we struggle. Currently over 2.7 % of the population are affected, ~0.9 % to the extent they cannot work, and this after just 2.5 years of the pandemic. What can we withstand? 5%, 10 %? I don’t know, but I cannot see a valid argument for testing the hypothesis that society can withstand X% of LongCovid. If you have one, let me know.

The Future 

Future A We continue to ignore the evidence, and see whether our society can withstand the impact of a large % of its population with LongCovid requiring care and being unable to work. This is a course of action taken by an ideologue, and is not possible for a scientist to act in this way, since in science we critically evaluate evidence.

Future B We apply mitigation measures so as to reduce the frequency of transmission, reduce infections and so the number with LongCovid, until such time as the pandemic is over and/or we have drugs that really work. This is the course of action of any organisation that has the well being of its staff (and students) as a core value, it is evidence- and knowledge-driven, and aims to be sustainable, that is to exist in a recognisable form in 10-50 years time.

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What is important for your career in the Faculty of Health and Life Sciences at the University of Liverpool

With Project SHAPE progressing in the Faculty of Health and Life Sciences at the University of Liverpool, we have now moved onto the compulsory redundancy stage. As a senior member of staff who went back to the trenches after ten years in management, I have been contacted informally by a number of staff who have been sent a notice that they are at risk of redundancy. So I used my experience in management and my knowledge of the University to figure what may be important for retention in the Faculty of Health and Life Sciences at the University of Liverpool and, perhaps more important, what may kill your career and result in a P45.

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I made my first New Year’s resolution on December 31, 2013: to only undertake reviews for open access and learned society journals.  This I have stuck to well, as I noted a year later for the simple reasons that it makes sense and it frees up my time.

Today I had a request to review a manuscript for Nature Publishing Group’s Scientific Reports, and I realised that I need to clarify my position.

I am on strike. (more…)

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This is a question raised at the end of the excellent article by @Amy_Harmon regarding Open Access and preprints is can biomedical scientists evaluate each other without journals?

The short answer is a resounding yes.  Physical scientists and mathematicians have been posting much of their research as preprints on arXiv for a few decades, with no prejudice to their ability to evaluate the quality of work or of individuals.

The counter argument raised by many in biomedical sciences, from scientists to some journal editors can be boiled down quite simply: We are special and cannot possibly do this.

Various arguments are put forward, from competition (=fear of scooping) to intellectual property. These arguments are heard in many biomedical/biology departments, sometimes leading to quite heated discussions. It is also interesting to note that the defenders of the status quo are not necessarily the older members of the community.

There is a simple answer. Yes you are special, but not in the good sense of the word. (more…)

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A tweet brought me to a PeerJ blog post on the uptake of open peer review. The post is worth reading. At PeerJ open review is an option – authors and reviewers can opt in or out, and only if both opt in is the reviewing history of a paper published.  One thing that caught my eye was that while 80% of authors opt in, the total number of paper with open reviews is just 40%, which indicates that reviewers are more reticent. (more…)

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This post assembles various comments I have posted and other thoughts on sci-hub and access to the scientific literature. It finishes with some ideas about what we should consider keeping and some of my better experiences, as a consumer and producer of the scientific literature.

Some time between clay tablet and the PDF

Once upon a time manuscripts were hand written, double spaced (fountain pen as ever outperforming all other tools), graphs transferred to tracing paper using a rotoring pen and Letraset (also alive and well) used for symbols. (more…)

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During a quick scan this morning of the “recent” comments on Pubpeer, an activity that I pursue regularly, as part of my reading, there seemed to be a lot more author responses.  So I counted.

70 articles featured with comments.

10 of these had an author response.

This is progress. I have no data, but my impression is that a year ago author comments were far rarer, maybe 1% or thereabouts. Now we are at 14%. Let’s hope this is not an anomaly, but a trend, and maybe in a few years papers without author responses will be in the minority.

Regardless of arguments about anonymity, etc., post publication peer review is growing, which is a sign of health in the scientific enterprise.

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Much has been written about the peer review process and its flaws. Richard Smith, a former editor of the British Medical Journal has stated that since peer-review doesn’t work, we shouldn’t do it

I have recently come across another example of the flaws in peer review. I reviewed a manuscript last year and identified what I believed to be technical problems and suggested at least major revision. The other two reviewers agreed; the three of us had homed in independently on the same technical issues.

Move forward a year and the paper is published in another (equally “prestigious”) journal, no changes.

So I will now amend my New Year resolution (still holding firm) from 2014 and 2015.

In addition to only reviewing for open access journals, I will from now on only review for journals where the review is open and published or where I am free to publish the review. That, at least, will avoid the ethical tension between participating in anonymous peer-review and then wanting to publish the critique when nothing has changed in the paper.

Why Groundhog day? This is not the first time I have had this experience.

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Of nanoparticles, cells and polyanions

It is the end of semester 2 so it’s marking season. Since we double mark (a good thing), the final year research projects are marked by both supervisor and an assessor, a member of staff who is not involved in the project. One of the projects I marked was Gemma Carolan’s on “How do SmartFlares RNA detection probes reach the cytosol? Available are the PDF of report, and posts here and here.

I had a sense of déjà vu while reading the project – the clear endosomal location of the SmartFlares, regardless of the DNA sequences brought me back to the days when antisense was the technology of the future for medicine.

While evaluating new technology it is useful to go back and look at other high flying technology. The reality is that it takes decades before we know whether the promise (and hype) were justified; this is true for any hot topic from stem cells to nanoparticles and graphene.

Antisense effects can be mediated by RNAse H, an enzyme that specifically cleaves RNA-DNA duplexes and which protects our cells from RNA viruses. There are other mechanisms, e.g., interference with splicing or translation, but the RNAse-H mediated transcript degradation should be central to many antisense effects. There were many papers reporting specific effects (evidenced by differences between sense, antisense and scrambled oligonucleotides sequences). These certainly contributed to success of individuals and of institutions, e.g., in UK Research Assessment Exercise and grant awards.
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I am a fan of PubPeer, as it provides a forum for discussion between authors and the wider community, something I have discussed in a number of posts (two examples being here and here). Two days ago, My colleague Mike Cross came by my office, having just delivered a pile of exam scripts for second marking (it’s exam and marking season), asking if I had seen a comment on our paper on PubPeer. I had not – too many e-mails and too busy to look at incoming!
So I looked at the question, which relates to panels in two figures being identical in our paper on neuropilin-1 and vascular endothelial growth factor A (VEGFA) – indeed they are labelled as being identical.
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