Monday, 28 December 2020

Opportunities, Challenges, and Considerations related to laboratory reporting of infectious diseases to Public Health England


Considering that Infectious Diseases, especially those deriving from zoonotic sources, currently contribute approximately 20% of the global annual death causes and 10% of the total disease burden in the European continent [1]; and that the likely losses of a pandemic influenza outbreak could reach 3 trillion American dollars (~5% of the global Gross Domestic Product) [2], the different states within the European Union decided to prioritise health areas that include proactive monitoring and reactive responding, with special focus on antimicrobial resistance (AMR), vaccine preventable diseases, tuberculosis, influenza, and sexually transmitted infections. 

In this respect, it is crucial to understand the pathway that takes data to realistically travel from clinical laboratories onto integrated-monitoring pieces of highly advanced software, as it is, the case with national governmental agencies (e.g., Public Health England). The disease surveillance program commissioned by Public Health England (PHE) covers 37 infectious diseases, including influenza. 


Clinical microbiology laboratories (CMLs) demonstrate their ability to:

o inform and improve individual patient care, 

o contribute to outbreak management and hospital infection control, and 

o provide accurate surveillance data on infectious diseases and AMR. This information can be subsequently used in the reviewing of local treatment guidelines and the designing and evaluating of national health policies. [1]

In that sense, In vitro diagnostics play an important role in the scrutinising process - There are at least three major areas where in vitro diagnostics can provide essential contributions to diagnostic reasoning and managed care of patients with suspected or confirmed infection:

o aetiological diagnosis, 

o patient monitoring, 

o and epidemiologic surveillance. [3]

With special interest in the Reporting of bacterial and viral infections - In general, we can segregate the detection of viruses into three main categories: 

o direct detection of the virus, 

o viral RNA/DNA detection, and 

o antibody detection. [4]

Data reporting feeds two very important surveillance systems, the UK Biobank (UKB) (an international health resource  with 500K subjects allowing research into the genetic and lifestyle determinants of common diseases), as well as the Public Health England’s Second Generation Surveillance System (SGSS) (a centralised microbiology database covering English clinical diagnostics laboratories) participate in the national surveillance of highly relevant notifiable infections, bacterial isolations, and antimicrobial resistance. [5]

Analysis of shared data fed into these systems allows an improved management of relevant epidemiological scenarios based on:

o Rapid early detection validated by a large number of samples with high accuracy diagnosis supporting an enhanced surveillance.

And this process will synergistically assist the:

o Review of local treatment guidelines, and the

o Evaluation of National Health Policies


There are many challenges associated to laboratory reporting within the public health surveillance system: 

o Data artifacts - missing, inconsistent and implausible data; gaps in data transmission;

o Constant change of guidelines and instructions – rapidly changing indicators; 

o Heterogenous procedures - systematic differences between labs and in the utilisation of services; patient linkages over time, different data sources, numerous registries, and indicators, 

o Time burden for busy providers

o Idiosyncratic +/- reporting - even though false positive/negative reporting is associated to (A) a low concentration of antibodies usually present in fluidic samples; (B) presence of homologous proteins; and (C) lack of sensitivity from the detection instrument, the fact that not all negatives are reported and that not all are reported via the same reporting systems and to the same surveillance agencies, enhances the monitoring difficulties associated to the process. [3] [4]

o Shortage of resources for high volume/frequency testing

o Incongruent shipment to reference labs          

o Numerator-Denominator Incompatibility - a systematic distortion due to a denominator that does not match the numerator, or vice versa.

o Difficulties in exposure assessment 

o Inadequate/Insufficient Environment/Equipment

o Culture of lax charting (e.g., ISO15189, ISO17025) - Regulatory standards demand clinical laboratories to establish and document their own performance guidelines for laboratory-developed tests in order to make sure the obtained results are done accurately and with precision results, even prior to implementation of the test. The relevant aspects that are to be considered are: accuracy, precision, reportable range, reference interval, analytical sensitivity, and analytical specificity.


But not all illations are challenges, as the present times offer enormous levels of learning that can be brought to practice. Probably, the most important lesson that businesses learned from COVID-19 is the need for adequate remote working opportunities and capabilities (arguably the greatest practical legacy left behind for business owners to read).

The first and possibly the most important lesson that policymakers and hospital administrators MUST learn from COVID-19 is that the continuing cut down on human and economic resources generates a huge impact in the healthy functioning of structures that can easily lead to collapse of the public/private health system, including the clinical laboratories with their enhanced testing demand. [3]

Established labs are an important resource 

The linkage of COVID-19 test results to the UKB provides an invaluable resource to the international research community that has the potential to uncover new risk factors for severe infection. UKB is one of the largest and closest-studied cohorts in the world. [5]

Biomolecular data exchange between databases - As is so well stated in Lenert and Sundwall (2012) "Clinical providers must exchange specified types of data with the public health system, such as immunisation and syndromic surveillance data and notifiable disease reporting. However, a crisis looms because public health’s information technology systems largely lack the capabilities to accept the types of data proposed for exchange. Cloud computing may be a solution for public health information systems. Through shared computing resources, public health departments could reap the benefits of electronic reporting". [6]

IT infrastructural autonomy - It is understandable that each organisation wishes to maintain its autonomy, however and for the sake of a prompt positive intervention, such is completely impracticable in a diasporic multifaceted system. The idea is even considered to be OBSOLETE [6] and goes against the prominent technological inflection dictated by 'democratic' and very functional cloud services.


Ten final considerations are therefore learned and directly cited from the available literature (for sake of authenticity in origin), and hereby listed adding to the brainstorming of a surveillance system able to work effectively if so by all input sources:

"Establishment of an efficient network of regional clinical laboratories, involving those which are not directly challenged by the outbreak and where samples can be conveyed, is a feasible solution, provided that a straightforward regulation for specimen transportation and biosafety is set and monitored. This, in turn, highlights an unavoidable need to place major efforts for allowing better and wider harmonization of laboratory results and information, encompassing both analytical and extra-analytical issues." [3]

Efficient communication to appropriate stakeholders - "It is essential that the laboratory personnel be instructed to communicate test results to the appropriate stakeholders (i.e. to the people who are officially in charge of dealing with the outbreak), thus avoiding to spread information that could generate unjustified panic, or inappropriate reassurance, among the general population." [3]

Accurate diagnosis VS Patient stigmatisation - "Achieving, maintaining, and improving accuracy, timeliness and reliability of test results are key deliverables of diagnostic laboratories. Late or false-negative SARS-CoV-2 test results will lead to delays in or even preclude correct diagnosis, jeopardizing timely isolation and prevention of transmission. In turn, false-positive tests will waste public health resources, will lead to incorrect epidemiologic data, and might even lead to patient stigmatisation. Quality control is a cornerstone of safe, consistent, reliable diagnostics, and many studies and frameworks outline the structure of quality-management systems suitable for diagnostic laboratories."[7]

Integration into biorepositories - "The significant role of the CML networks should not be underestimated in the sharing of routine clinical metadata or data collected. Their potential integration into a common data set (biorepositories—as proposed by the Clinical Data Interchange Standards Consortium) would maximize the opportunities for patient contributions to be translated into therapeutic and diagnostic solutions. The consolidation process for example provides a tangible opportunity to extend the scope of pooled analyses of individual patient biomarker data from heterogeneous laboratory platforms and cohorts into population-level studies using merging algorithms." [1]

"The availability of commercial diagnostic kits in peripheral centres shall be part of the strategy for early and accurate identification of the largest possible number of infected patients." [3]

Locally - "Near-patient testing would include so-called 1- to 2-h “plug-and-play” nucleic acid amplification tests for which a rapid result can directly impact patient care. Centrally - More-complex/high-volume tests would be dispatched to a core facility. In addition, the ability of networked CMLs to access multiple different partners, geographies, and clinical specialties can enhance their capabilities to provide advanced disease surveillance and early outbreak recognition." [1]

Harmonised SOPs - "Laboratory professionals may also be made available on-site, where they could help define standard operating procedures (SOPs) for specimen collection and transportation. The choice between these possible solutions will obviously depend on many economic, legislative, juridical, logistical, environmental, and technical issues." [3]

Same-day direct assays - "A major advantage of the consolidated CMLs is the expansion of the range of activities, able to accommodate high technology and sophisticated tests with increased sensitivity and specificity (30), while the usual day coverage is extended through a second (and third) shift. Same-day, direct assays, including molecular assays for selected organisms, are performed as a matter of routine thus reducing time to obtain results." [1]

Inherent system flexibility - "The availability of increased amounts of high-resolution data at a lower cost creates an anticipation, requirement, and downstream cost(s) for the accommodation, analyses, and interpretation of these data. The inherent systemic flexibility that is necessary to receive different types of data at different speeds and from different locations—and link all that to routinely collected clinical data and report back—is not an insignificant task by itself." [1] 

Ethical implications of big data analysis - "A number of questions are raised regarding the new pathways that might be necessary, the different regulatory approaches within Europe to handling this data under the EU personal data protection directives, and data quality issues. If not correctly addressed by the inclusion of ethical design in the creation of big data, such ethical issues might become limiting factors preventing reaching of full potential." [1]


[1] Vanderberg, O., Kozlakidis, Z., Schrenzel, J. et al (2018). "Control of Infectious Diseases in the Era of European Clinical Microbiology Laboratory Consolidation: New Challenges and Opportunities for the Patient and for Public Health Surveillance". Frontiers in Medicine, 5(15), pp. 1-7.

[2] Gebreyes, W. A., Dupouy-Camet, J., Newport, M. J., et al (2014). "The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings". PLOS Negletected Tropical Diseases, 8(11), e3257, pp. 1-7.

[3] Lippi, G and Plebani, M. (2020). "The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks". Clin Chem Lab Med, 58(7), pp. 1063-1069.

[4] Bhalla, N., Pan, Y., Farokh, A. (2020). "Opportunities and Challenges for Biosensors and Nanoscale Analytical Tools for Pandemics: COVID-19". ACS Nano, 14, pp. 7783-7807.

[5] Armstrong, J., Rudkin, J. K., Allen, N et al (2020). "Dynamic linkage of COVID-19 test results between Public Health England’s Second Generation Surveillance System and UK Biobank". Microbial Genomics, 6, pp. 1-9.

[6] Lenert, L., Sundwall, D. N., (2012). "Public Health Surveillance and Meaningful Use Regulations: A Crisis of Opportunity". American Journal of Public Health, 102(3), pp. e1-e7

[7] Homolka, S., Pawlowski, L., Andres, S. (2020). "Two Pandemics, One Challenge— Leveraging Molecular Test Capacity of Tuberculosis Laboratories for Rapid COVID-19 Case-Finding". Emerging Infectious Diseases, 26(11), pp. 2549-2554. 

Friday, 20 November 2020

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

Thursday, 19 November 2020

Did you know that ...

 

Altmetric is a tool that allows you to collect and collate research information spread out in the web using a really helpful interface that provides you information on how your own research is seen by others. This is a very useful tool for those scholars who publish, for investigators and even institutions, those who provide grants and those are involved in R&D. Finally a tool that makes all engage in the same platform whilst compiling relevant and useful data on their investigational projects. More information HERE.


Chronic fatigue in Sjogren's syndrome patients - it is known that chronic fatigue in patients dealing with Sjogren's syndrome is probably one of the most invisible debilitating traits of this set of 'diseases'. But a recent article has shed some new light on an agent that interferes with the immunological response and consequently on fatigue, the vagus nerve, that can be used to modulate the immune responses, and with the help of an electronic device, the noninvasive gammaCore. Initial results on a small number of female patients observed positive changes to the profile of fatigue and on the Epworth sleepiness scale (used to diagnose obstructive sleep apnoea) [1]. Reduction in these profiles were also accompanied by significant reduction in the presence of inflammation factors such as IL-6, IL-1β, IP-10, MIP-1α, and TNFα. More information HERE.


Free Resources for Science Pictures - Do you have a blog? Do you participate in a videocast? Are you writing a monograph, essay or any science piece of work that could use some visual attractiveness? Do you need science images but don't really have the money to pay for it. Well, this is the place where you have to go to. This platform suggests 7 places containing high-quality scientific research images that one can access and use at will. From figures, to micrographs, plots and diagrams the images available at the recommended sites will save one hours of unnecessary drawing up. More information HERE.


First Universal Flu Vaccine -  Now that the eyes of the world are layed upon the recent announcement of a vaccine to counteract the sars-cov-2 disease (covid-19), we nearly forgot that there are still numerous 'bugs', prions and viruses out there, roaming at will, looking for an opportunity to prevail. Influenza is just as such one of these and the research for a universal vaccine to prevent flu has been a long standing project. But in 2018 it was announced that the seasonal flu would meet a new defense guard, one that could even protect us against a emerging influenza mutation and avoid a pandemic. Approximately 20 years took these researchers to get to the phase III clinical trial stage where a new complex substance that induces immunity to the less varying parts of the virus (the core of the virus we would say), is to be tested on hundreds, or possibly thousands of human subjects. Knowing that the Influenza virus is made of two surface glycoproteins: hemagglutinin (aiding cellular access to host's moiety), and neuramidase (aiding the spread through), the new pipeline vaccine - BiondVax’s M-001 - will not focus on generating antibodies against the highly variable head of the virus, but instead focusing on producing an immune response against the stalk (a more conserved fragment in the viral structure). In fact, this project is so well advanced and scientifically robust that the researchers are also looking into adjuvants (substances that can aid the primary product work better in an improved fashion). On tof the adjuvants is called TRAC-478 and stimulates several toll-like receptors (TLRs) on antigen-presenting cells; the other one is known as TRAC-478 and can help the body recognise both bacterial and viral infections in a synergistic operation [2]. More information HERE.


The Language of Biosimilars - Have you ever heard of biosimilars? Have you ever been prescribed one? Well, to ignite your responses let us look briefly into what a biosimilar medical product is. A Biosimilar Medical product is a biological medicine considered highly similar to yet another already approved biological medicine (that for that matter is known as the 'reference medicine') and that are approved/licensed with exact the same standards of pharmaceutical quality, safety and efficacy that is applied to all biological medicines. In fact the same agency, meaning the European Medicines Agency (EMA) is the one body, in Europe, responsible for evaluating most of the applications to market biosimilars in the European Union (EU).

The active substances found in biosimilars, meaning the molecules that are indeed expected to do the trick and help cure the problem, are often purified proteins obtained from other living cells or organisms, such as animals, plants, or even smaller ones (microorganisms). The process of protein purification enhances the quality content of the product so the product can be used safely in responding to clinical needs usually related to chronic conditions.  

Confused? Biologic drugs are large, complex proteins, they are 'manufactured' from living cells in extremely complex manufacturing ways; but they are not what we know these days as generics. Roughly said, Generics are 'copy-paste' copies of chemical drugs where as Biosimilars are copies of a biologic medicine that is similar, but not identical, to the original medicine.

Considering that biologics are usually quite large 'protein' molecules with complex structures, biosimilars cannot be considered generic equivalents to these. Instead they are products developed and assessed for their efficacy and safety based on very rigorous processes that study their specific function in different steps of a clinical trial set to confirm similar efficacy and safety. These studies are not performed, or should not naturally be, to show clinical prevalence of these products. [2]


[1] Epworth sleepiness scale - Obstricive Sleep Apnoea (OSA), British Lung Foundation, [https://www.blf.org.uk/support-for-you/obstructive-sleep-apnoea-osa/diagnosis/epworth-sleepiness-scale], last access on the 19th of November 2020, last update on May 2016.

[2] Declerck, P., Danesi, R., Jacobs, I. (2017). "The language of biosimilars: Calrifications, Definitions, And Regulatory Aspects. Drugs, 77, pp. 671-677.

Monday, 19 October 2020

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

Friday, 25 September 2020

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

Tuesday, 22 September 2020

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

Saturday, 19 September 2020

The science of our days - a post a day!

I've been reading a lot of stuff during this crazy year of 2020, but haven't had the chance to compile and make sense of all the relevant information. I thought of  using the blog to aid me in the task of updating myself on the many levels of scientific information that I've been gathering throughout 2020 (yes, not all is covid-19 in the world, I promise you). 

In that sense and in the coming weeks until the very end of December 2020, I'll be posting a summary a day of quite short (500 words) and straight to the point chronicles addressing a magnitude of different savory scientific topics. 

I leave you with a small list of what is to be discussed and that will definitely entice you all to visit the blog... every single day (starting this Monday the 21st of September so pin it on your calendar):


  • Who’s talking about your research?

  • The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue and Immune Responses in Patients With Primary Sjögren's Syndrome

  • This medication for high blood pressure "increases the risk of lung cancer"

  • Life Sciences Industry Employee Engagement Report 2018

  • Are ketogenic diets really useful in treating cancer?

  • 7 Resources for Free Science Pictures

  • First Universal Flu Vaccine to Enter Phase 3 Trial

  • The promise and peril of gene drives

  • The toxin from a ParDE toxin‐antitoxin system found in Pseudomonas aeruginosa offers protection to cells challenged with anti‐gyrase antibiotics

  • Everything is awesome: Don't forget the Lego

  • One million mosquitoes and 500,000 tests later, new buzz about a malaria prevention drug

  • Major breakthrough in quest for cancer vaccine

  • New research: screen time is changing childrens brains

  • PANINI: Pangenome Neighbour Identification for Bacterial Populations

  • Annual Report to the Nation on the Status of Cancer

  • Ranking the 10 Best Survival Kits of 2020

  • 10 Most Dangerous Antibiotic-Resistance Bacteria

  • Recommended composition of influenza virus vaccines for use in the 2019-2020 northern hemisphere influenza season

  • The woman who took on Rockefeller

  • OPAT: Outpatient Parenteral Antimicrobial Therapy

  • What is CAR-T therapy?

  • The Rise of the Scientist Bureaucrat

  • Science Says Drinking Coffee Helps People Slow Aging, Lose Weight, and Cheat Death. These Fascinating Studies Explain Why It's a Miracle Drink

  • Micafungin treatment and eradication of candiduria among hospitalized patients

  • How stress contributes to autoimmunity-lessons from Sjögren's syndrome

  • COVID-19: some unanswered questions

  • How Do Food Manufacturers Calculate the Calorie Count of Packaged Foods?

  • Stress Hormone Causes Epigenetic Changes

  • Decoy antibiotics could get around bacteria’s defences
  • Sugar and cancer – what you need to know

Photo by Clay Banks on Unsplash