On the validity of a second lockdown in the UK

I believe I have stated many times before that I don't like fashion science TV, in the sense that it keeps talking exhaustively about a topic mumbling and chewing up on things that have been explored/exploited many times before, and actually outputting very little of novel valid information for the public. UnHerd TV is the opposite of this, at least, most of the times! And this is why I like to regularly look up on what they're debating because their broadcasts scrutinise real science, from real scientific backgrounds, supported by real scientific tools and opinions of really experienced science people. 

Recently, I came across an interview with Professor Tim Spector, an epidemiologist involved in the project development of an application called ZOE app. This is allegedly an app funded by the British government and that became quite popular over the past weeks for having already demonstrated that, prior to the decision of a second-imposed lockdown, the number of reported infected cases was already on a downfall.

In that sense, I committed myself to listening to the whole interview and collected the most relevant opinions that I personally believe can be demonstrative of what Professor Tim Spector, and also the UnHerd YouTube Channel have disclosed, meaning, THIS SECOND LOCKDOWN WAS UTTERLY UNNECESSARY!!! But why not read now the most revealing and relevant statements:

Who pays for the Zoe app?

The first 6 months were funded by Zoe in addition to the "citizen scientists" who were using the app and funded it. Then a fundraiser campaign came into place where about 70 thousand contributors helped maintain the app. Then in the Summer, the Department of Health started funding the project.

Does the funding by the government limit free speech?

Yes, in terms of what is said by researchers on social media, but not in terms of the data disclosed and shared in the app itself. Moreover, the researchers/scientists involved in the development of this project are not restricted in their freedom to criticise the government.

Was a second lockdown a needed approach in the UK?

If their Zoe app data had been taken into consideration, the governmental authorities would have made different conclusions and decisions considering that the data showed that, for some parts of the United Kingdom, a fall on daily reported covid cases was already a reality. That was already a reality when the UK was coming out of the tiered approach!

Even in tier 1 areas and immediately when the lockdown was decided and announced there was already a fall of in cases reported, ergo that downfall was not a result of the lockdown but already a trend that was taking place.

Different studies where the government based their decision on (e.g., Face value, REACT and ONS [the government official survey] operated almost as a decoy driving the government to such decision).

How did we go from one scenario to the other when grave impact on businesses and people lives were a risk?

Because no alternate views were shown and it was decided by the government to operate on a worst-case scenario prospect.

The fact that most likely during meetings with SAGE (Scientific Advisory Group for Emergencies) the government wasn't presented with an optional plan, resulted in unavailability of options for the former. But since there is inadequate information coming from those meetings to the public, this is just speculation.

What additional risks came in with the second lockdown decision?

Loss of quality of life in terms of physical and mental health (number of suicides, extreme anxiety and depression cases), less medical appointments for the common population or special population (cancer, stroke, heart attack patients, and the like), loss of longevity, loss of economic growth or just maintenance of financial stability was not even considered, and that is an undeniable fact. And the general media supported this idea by being blunt as to just focusing on the number of confirmed cases and the number of deaths covid-wise. It's like for them the only important factor was a body count. As referred by Prof Tim Spector, "in most Novembers and Decembers in the UK, 50 thousand people die; these numbers are actually trivial compared to the expected rates. As an epidemiologist, and there are a number of people who think like myself, we should be taking a much broader view of this" and "politicians and scientists only seem to be punished when we underestimate [...] in society we are very risk adverse". There was no balancing of the different impact on different sections of society.

Were the curves coming down because of a greater degree of immunity in the population?

From what has been observed in other epidemics this is a natural occurrence as infection rates don't simply go up constantly, they respond in waves; these infections tend to lose strength when they've infected enough people or when infected new people; the infection meets an enhanced immunity against the viruses. It is possible that in certain places people who did not self-isolate or did not respect social distancing and did not get infected were indeed already immune, an immunity that is recognised to be on average present for 6 months. Different views can support different ideas in different regions showing different curves, what Prof. Tim Spector said of "micro-arguments".

Why has the conversation between sections of society and authorities become so poisonous?

Clearly not all information has been shared which created discredit in many sections of society. Decisions were made as to not discuss more than compliance, a restricted number of symptoms, "there was only two symptoms until the Zoe app uncovered the loss of taste and smell, other countries have much broader ideas and do share more".

Will lives go back to normal in Spring 2021 now that a vaccine has been announced?

"It's great to have some optimism. We have a vaccine that looks like it may work which means that if that one doesn't others will probably do. I think it's dangerous to think this will be actually working for us in the Spring; we don't know how long it lasts [...] whether it works on old people [...] We do need a plan to go back to normal to accept that continued infections and continued deaths are here for the rest of the year".

Should this new vaccine be administered on a voluntary- or mandatory-basis?

"[...] the number one group to sort out are the vulnerable. Cover them and their carers, we could effectively shield them pretty well and everyone could just put up with the virus apart from some cases of long covid; we could cope as a country and get economically back to normal [...] I think we try a voluntary approach... once we know more about it as all these vaccines are very novel... once we know more about the risks people are taking, people wouldn't necessarily accept that and one thing we are doing in the app is adding a vaccine function to it where people could take the vaccine and report the long term effects to it to feel safer about it themselves".

For downloading or just reading more on the Zoe app, please access HERE.

For viewing the full interview yourself please access HERE.

1st image kindly taken from UnHerd TV.

2nd image by by Matt Seymour on Unsplash

Herd Immunity - the unheard of approach for managing this Pandemic

By the start of this corona virus pandemic, my wife and I sat down and immediately agreed that in order to save the global economies, one would have to make concessions, and the most difficult one is who to save. Amid a pandemic it's impossible to fix the Titanic, save every one on board, take them to a comforting safe place and allow the band to play amusingly throughout the whole process. Life is just not like that, and only politicians like to portrait reality as a do-or-die strategy. That only works in two basic assumptions, 1) when they have no idea how to fix the issue and need to show voters they are still in command, 2) when they want to publicise the Armageddon as near and somehow their incredible wits are here to save the day and rescue us from the abyss. Both assumptions only work with dumb people who don't offer a second to deep thinking and are fairly hypocritical in fallaciously attempting to show control of the supposed unknown. 

As I was initially saying we had immediately understood, not because we are incredibly clever but because we are not easily decoyed by small talk, that herd immunity would be the only capable approach to reduce the overall damage whilst allowing the limited available strengths to focus on risk groups and those most in need of support. But Hell no, a primitive approach with no previous example of success was immediately put in place as the only feasible concrete strategy to contain the supposedly unfamiliar invisible enemy. Some of our friends criticised us for lack of democratic heart, for a heartless artificial selection of those who should be living, and liberally shouted the need to protect lives before economies, as if things weren't immediately and directly linked synergistically.

Before such aggressive response from others we refrained to disclose more vividly our opinion on herd immunity, especially because the concept itself was so falsely dilapidated of sense that somehow turned into an irresponsibility of the ignorant rather than having its logic presented to the public in an adequately scientific fashion. 

But luckily, more and more scientists started gaining the correct timing and plateau to display the positives of such understanding of what life is and must be, an intricate complex web of valences that intertwine and interact naturally by means of forces that are prompted by stimuli inputs, by all of us, viruses included. And this feeding of stimuli learns from its inter-relations as it unfolds, it is not a closed environment and it is not an immutable one. One must go on actively learning the inferences to predict fast and apply strategies for more positive results. 

Many have ridiculed the idea of a herd immunity basically because the idea itself never had time and a stage to properly disclose the ins and outs of the approach. But that changed since the meeting of three expert scholars, expert epidemiologists (read their names and their respective alma matter at the end of the post) who met in agreement for redacting a declaration pro-herd immunity approach. They fairly and thoroughly explained the reasons for their meeting and the final objective in the shape of a declaration that I hope you can sign and pass on, if you agree with the principles of it; but the most important part of it is the scientific backing of all they say, contrarily to the verbiage that some State Representatives constantly make use of and that is supported only by their political agenda.

Please find below the most relevant aspects of the video I analysed for you and I hope that the words of these three experts do indeed alert people to the most relevant fact that is presented to us by this pandemic - our lives must go on whilst protecting the most vulnerable ones, but not at the expenses of All, but with the participation of ALL. Especially in this day and age where people who have the disease are being stigmatised, and us forced to believe that it is perfectly acceptable to be imposed by governments in accepting a fully Orwellian control/track application that deeply offends your privacy and freedom, backed by the ridiculous fact that supposedly we already offer so much of our privacy away by using social networks that this would not be a massive sting to our already deeply wounded dignity/identity: 

A) The approach taken on tackling covid-19 has produced enormous collateral damage, e.g., less cancer screening, less vaccination rates, less medical appointments.

B) There is need for a continuous herd immunity so the most vulnerable can be taken care of whilst young people and those who are not high-risk can continue with their lives.

C) Herd immunity is not a strategy, herd immunity is a fact across numerous diseases that spread in the human population.

D) Even when we have a vaccine we would be relying on herd immunity for this epidemic.

E) Herd immunity is a recognition of a biological fact, not a strategy... There is a misconception when people hear the words 'herd immunity'.

F) The proposal offers concrete ways to address the needs of the vulnerable... The premise is not to do something reckless, the premise is to take account of all the public health.

G) The key thing is that whatever strategy we use, we will reach herd immunity so we should be taking care of the most vulnerable... and there is various ways to do this, e.g., in nursing homes (with frequent testing and less turnover among the staff); teachers above the age of 60 should be working from home but there is no reason for a teacher in his 30s to avoid going to work.

H) We can never protect people 100%. We should move towards this regime [herd immunity] immediately, remembering this would not be a permanent state of affairs, but a period of approximately three months that would take for the virus to sweep through the population. It's a fundamental feature of the pathogen as the kind of infection period that sars-cov-2 has that it should rise-peak-drop off in that sort of period, and this has been observed in many countries... Then we would reach a time when the most vulnerable wouldn't see the younger ones as a danger. The policy that we currently have extends the period where the grandmother and granddaughter need to be distanced from one another. The herd immunity strategy is more humane. 

I) A focused protection expands freedom in the sense that it allows one to re-engage. Freedom is important but we need an informed freedom.

J) With the current focussed approach [taken almost globally] we are protecting low-risk college students and low-risk adults in privileged classes while placing on the poor classes the job of generating immunity that will eventually protect all of us, especially on the backs of the urban working class.

K) [With the herd immunity approach] an over 60s bus driver would not work, he would take a sabbatical with social security support, and other welfare support, for three to six months until immunity would [surface].

L) The present strategy [used by the different governments] exposes poor people to risk whilst protecting the rich. Herd immunity promotes equality while the present strategy promotes inequality. Science and morality must point in the same direction in what concerns public health... Lockdown was pure damage to society.... 130 million people would starve to death if a new lockdown is imposed. 

M) The present difference risk between youngsters and elders is a 1000-fold in terms of mortality, and this is the weakness of this pandemic that \needs to be used in our advantage.

If you'd like to listen to the video conversation of the three experts who participated in the preparation of this declaration, please access the UnHerd TV video here. TO SIGN THE DECLARATION, please ACCESS HERE.

***

Dr Sunetra Gupta is a professor at Oxford University, an epidemiologist with expertise in immunology, vaccine development, and mathematical modelling of infectious diseases. [1]

Dr Bhattacharya is a professor at Stanford University Medical School, a physician, epidemiologist, health economist, and public health policy expert focusing on infectious diseases and vulnerable populations. [1]

Dr Kulldorff is a Professor of medicine at Harvard University, a biostatistician, and epidemiologist with expertise in detecting and monitoring of infectious disease outbreaks and vaccine safety evaluations. [1]

[1] Covid experts: There is another way, Unherd TV, [https://unherd.com/2020/10/covid-experts-there-is-another-way/], last update on the 5th of October 2020, last visited on the 18th of October 2020.

Photo by Ryoji Iwata on Unsplash

Differences between pneumonitis occurring with immunotherapy and COVID-19

I've recently took some new training courses as part of my professional role as a medical information specialist, and in one of these I was lucky to be clarified on a current and important aspect related to COVID-19:

On the differences between pneumonitis occurring with immunotherapy and that of COVID-19

The information we were provided relates to what was known by then and might not be the most up-to-date at the time you might be reading this post, so please keep that in mind before assuming the details hereby shared with you are still actual.

Why is it important to understand such differences?

Because as for any chronic patient and due to the impact on the immune system of cancer patients (especially lung cancer ones), their risk of developing lung complications is much higher than for regular patients. In addition, COVID-19 also has the potential to trigger pneumonitis, and therefore a clear diagnosis must be conducted to differentiate.

What are the symptoms of pneumonitis in these groups?

Typical symptoms reported by cohorts from China and Europe refer dyspnoea (difficult breathing), pain, and other symptoms like cutaneous, gastrointestinal or endocrine ones (related to hormonal release); but it is cough, the pain profile and pyrexia (increased body temperature above what is believed to be the expected normal) that sees increased incidence in COVID-19 patients (in comparison to the other group). 

Timing and onset of symptoms is a very important aspect to retain!

Even though, times are not to be taken as absolute indicators for any of the groups, cancer patients reveal peak points with the highest toxicity grade (namely, colitis and pneumonitis) at about 6 and 12 weeks, respectively), whereas for COVID-19 patients the incubation times sits at an average of 4 days.

What other differences have clinicians observed?

In immune-related pneumonitis, the radiological aspect is of peripheral ground glass shadowing that tends to affect the lower lobe specifically; and is almost universally bilateral. This scenario evolves as disease progresses to a more severe condition. Because there is no specific test to scrutinise for a immune-related pneumonitis it might be relevant to associate to all the reported differences a few other relevant tests, such as, a lymphocyte count expected to be normal or higher than normal values in immune-related pneumonitis; also the presence of more than normally expected values of C-reactive protein (CRP) (a protein produced by the liver in response to inflammation), and even more than normal values of sedimentation rates for erythrocytes (usually these red blood cells sediment quite slowly in a normal subject, but for a body fighting with inflammation the sedimentation rate would be faster than expected). Finally, cancer patients undergoing pneumonitis would present with a bronchiolar lavage displaying prominence of eosinophils and lymphocytes.

As to pneumonitis in COVID-19 patients the first line of testing would immediately be the genetic/antibody recognition of the presence of the virus, by means of PCR, after a nasopharyngeal test. But at best this recognises the virus up to a sensitivity of 70-80%. In case of a negative test, a false-negative cannot be ruled out, so subsequent tests are then applied in order to positively affirm of the presence of the virus in patients suffering of pneumonitis, namely, a battery of tests known as liver function tests:

- the LDH test that is typically used to determine in a more accurate fashion where a certain damage is organ-located and the severity of the disease progression, 

- the creatinine kinase test to assed whether the pathology is of a cardiac or skeletal muscle nature (that in association with the troponin test provides a better understanding as to whether damage of the cardiac tissue has taken place); 

- by also checking the aforementioned inflammatory markers described in the paragraph below (especially when considering that clinicians recognise typical values around 100-150 mg/L, 

- a D-dimer test to check on the occurrence of blood clots (where they have noticed that in severely sick patients this indicator is quite elevated - even though such is not specific of thromboembolic disease, but can indicate severe inflammation);

But be sure that the variety of tests available for diagnosis is large and I cannot immediately discuss them all in detail hereby. However, I'd like to add to the pool of exams yet another one the clinicians mentioned, the Beta-D-glucan test that helps them rule out (or not!) pneumocystis infection with fluid buildup in the patients lung.

In summary

Differences and similarities exist between pneumonitis in these two populations of patients, but clinicians have plenty of biochemical options to scrutinise the profile of a immune-related pneumonitis from that of a pneumonitis caused by the new corona-virus.

Photo by CDC on Unsplash

A variant of SARS-CoV-2 can still be out there, and we may be the lucky ones to get it

A friend of mine has brought to my attention an article recently published on the effects of a major deletion in the SARS-CoV-2-genome [1] (the coronavirus genetic pool, let's say) on the severity of infection and its associated inflammatory response. We discussed it with a lot of interest, considering all the positive predictions such implications would have in the outcome of this very disturbing and concerning pandemic. And even though the article focus on a cohort study based in Singapore, meaning just a limited sample in a specific constricted time and space was analysed, certain 'extrapolations' could help foresee or predict positive outcomes. 

The researchers studied variants of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) at seven public hospitals by retrospectively identifying patients that had been screened for the Δ382 variant. And then they compared these with the ones infected with the wild-type. But what is the difference between this Δ382 variant and the wild-type? For those who are not familiar with genetics, imagine that the wild-type is the very first virus that presented itself to us humans, as wild as one can find it, straight from the jungle, no changes to its genome as this would be the very first of all. Then we have the Δ382 variant which is the wild-type but with something different, be it added or removed, like a car with three or five wheels. 

It happens that this Δ382 variant has something less than the wild-type, i.e., a deletion that truncates (slices a bit of a bigger important structure), and the researchers realised that this deletion possibly impacts on the virus transmissability and also on its virulence. In addition, they even realised that the structure affected by such deletion is the ORF 7b (an open reading frame - part of a reading frame in the genome that has the capacity to be translated) and consequently removes the ORF8 transcription-regulatory sequence of the genome. The result is a Δ382 variant  of SARS-CoV-2 that is likely to be associated to a much milder infection because this variant might be less effective at infecting a new host since the ORF8 structure is linked to lessened inflammatory potency. Why? Because the removed bit is a 82 nucleotides and 415 nucleotides in a very important genomic section, even though the biological function of the ORF8 protein in SARS-CoV-2  is still to be clearly known and described. But further in-vitro analysis have also shown that said deletion does not affect the replicative fitness, meaning the capacity for the virus to go out there and multiply like little crazy hot hormonal rabbits.

But again, what are the implications in terms of symptoms revealed by sick people infected with variant Δ382? When researchers compared people infected with this variant alongside those infected with the wild-type only, five aspects were quite clear and promising in the way that they add in to understanding how a pharmaceutical could be developed in the future; not to vaccinate but to inhibit/repress the viral protein proneness of this pandemic agent:

1) In terms of fever, those infected solely with the wild-type are about 4.2-fold more prone to pyretic effects... that is quite a difference!!!;

2) In terms of cough, an aspect that not only portraits a likely lung affliction but also impacts on the immediate transmissibility of the virus - those infected with the Δ382 variant solely are 3.1-fold less prone to reporting cough;

3) One of the most interesting aspects of this research is that they also studied the C-reactive protein concentration levels, a direct indicator of immediate inflammatory response. The more C-reactive protein the more inflammatory response. People infected with the wild-type only will have 2.07-fold higher levels of this inflammatory protein.

4) All together the observed data have also shown that the two most important traits in symptomatic patients, meaning hypoxia (lack of oxygen) and pneumonia (infection of the lung(s)) is tremendously reduced in those infected with the Δ382 in comparison to the wild-type, thus suggesting that this deleterious event that resulted in this mutant produces a much milder outcome.

5) This study finally concludes that the ORF8 can very likely become a successful target for a pharmaceutical or therapeutic strategy that studies this viral infection in humans. Event though the ORF8 deletion does not suppress the replicative capacity it does reduce the strength of consequences in the human body. And this is ever more important when we consider that this variant shows difficulties in attaching to a new host as the secretion of its infection proteins might be impaired.

And don't forget, this was the variant that was successfully transmitted in the early days of this pandemic even though the confinement and control measurements have wiped it prior to March this year. But lessons were learned so we can start applying the acquired knowledge for a future medical/pharmaceutical approach.

[1] Young, B. E., Fong, S-W., Chan, Y-H. et al (2020). "Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study". The Lancet, 396, pp. 603-611