Immunologist cautions on lead vaccines

17 November 2020

Byram Bridle, a viral immunologist at the University of Guelph, cautions New Zealanders that the lead vaccines against Covid19 may not be the solution they are expecting to end its isolation under the elimination strategy.

The main points of his caution are:

  1. NZ will have to wait at least two years before the Pfizer vaccine is available, because it is in strict isolation and low on the priority list for the 500m doses available in 2021.
  2. Not enough data has been released to know whether the vaccine prevents or weakens the symptoms of Covid19, or how long the protection will last.
  3. The safety data will be incomplete if it is approved for use next year, so monitoring will need to be carried out on vaccinated people for some years.
  4. The Pfizer data has not been rigorously peer-reviewed.
  5. There is no available data on the qualitative nature of the immune response. Vaccines like this can be misinterpreted by the immune system as an extracellular pathogen, which can cause them to respond poorly to natural infections with future coronaviruses.

“Pfizer’s vaccine is a RNA-vectored vaccine. This technology is relatively new and has not been approved for clinical use before. The company has been able to move surprisingly fast. If the recent data is indicative of what data from the rest of the trial will look like, there is a good chance the vaccine could receive emergency approval by early in 2021.

However, there are many nuances…”

Insufficient public data

“The study is only partially complete. There exists the possibility that the final data set will fail to secure regulatory approval (but it looks like they may be on track).

Data that accompanied the Pfizer press release was extremely superficial and, therefore, difficult to interpret. Data being collected for the Pfizer study cannot accurately be commented on until it undergoes rigorous peer review for publication in a good quality scientific journal.”

Effectiveness of protection

“90% effectiveness sounds surprisingly high. But we have no idea what the demographics look like. Although they opened the trial to high-risk people, we have no idea who contracted COVID-19. As an extreme example, if all the vaccinated volunteers that got COVID-19 were elderly and that number was not significantly different from the elderly among the non-vaccinated volunteers that got COVID-19, that would tell us that the vaccine does not work in those who need it most.

Most of the cases of COVID-19 in the study were presumably mild to moderate since no hospitalizations or deaths were reported, so we don’t know how protective the vaccine will be for those who are susceptible to severe cases.

There is no data regarding immunological memory, which is the entire point of a vaccine. If the memory response is weak or wanes too quickly, people will not be protected over the long term. This would be a fatal flaw because the global roll-out of a vaccine will take a very long time.

Pfizer hasn’t stated what the qualitative nature of the vaccine-induced immune response is. Sub-unit vaccines like theirs have been known to be misinterpreted by the immune system as being an extracellular pathogen. If that is the case, people who receive this vaccine might have a bias imprinted on their immune system that could cause them to respond to natural infections with future coronaviruses in a sub-par fashion.”

Two dose vaccine.

  • “It can be hard to get people back for a second dose. It is probably achievable in urban centres but could be hard to get the same people back 21 days later in remote and/or difficult-to-access places, especially in developing countries.
  • A vaccine that needs two doses is arguably a ‘weak’ vaccine. For this vaccine, it will take 28 days to build up sufficient protection. So there will be a one-month window during which people will remain susceptible. A better quality, single-dose vaccine could probably reduce this to 10-14 days.
  • Fewer than 500 million people could be vaccinated within a year of the vaccine being approved. The company is going to try to stockpile 50 million vaccines this year in anticipation of the vaccine being approved, and they optimistically predict that they can make 1.3 billion doses by the end of 2021. This sounds like a lot, but a two-dose regimen cuts the number of people that can be immunized in half. The person to get the 500 millionth dose will have to wait a year compared to the person who gets the first one. Some will wonder why some people get two doses while they get none. The vaccine won’t be protective unless two doses are given.”

Roll out internationally

“What about the rest of the population? As many of us have been predicting, it could take years to roll out these vaccines. Approval of a vaccine doesn’t help anyone; what matters is when it has been administered and sufficient time has passed for the immune system to respond. Of course, where in this very long timeline for the roll-out will countries that have used strict isolation to control their cases be (arguably, low on the priority list). Pfizer’s press release is essentially saying that everyone beyond the first half-million people will have to wait over 1 year. Presumably, it also means that people beyond the first billion or so may have to wait over 2 years.”

Long term safety

“Long-term safety in people is inferred based on animal models (such as rodents) that have shorter lifespans. Usually, clinical trials are done sequentially and span quite a few years. So acute and some long-term (i.e. 4 or more years) safety data would be in-hand. With the different trial stages overlapping and being run faster than normal, we will likely have less than a year’s-worth of safety data. Ultimately, the only way to be completely sure about long-term (i.e. beyond the duration of the clinical trial phase) safety in people is to monitor vaccinated people for a long period of time after the roll-out. Things like long-term kidney damage, etc. can often (but not always) be predicted/ruled out by things like blood chemistry within the acute stages.”

/ends

No appreciable risk of Covid19 infection from close contact with children

Another piece of evidence against lockdowns; research shows close contact with children under 11 has no increased risk of Covid19 infection, close contact with those 12-18 has a small increased risk of infection, while there was no impact on outcomes of being infected with Covid19. As a bonus, closeness to children reduces non-Covid19 deaths….

Working on behalf of NHS England, we conducted a population-based cohort study using primary care data and pseudonymously-linked hospital and intensive care admissions, and death records, from patients registered in general practices representing 40% of England. Using multivariable Cox regression, we calculated fully-adjusted hazard ratios (HR) of outcomes from 1st February-3rd August 2020 comparing adults living with and without children in the household.

Findings Among 9,157,814 adults ≤65 years, living with children 0-11 years was not associated with increased risks of recorded SARS-CoV-2 infection, COVID-19 related hospital or ICU admission but was associated with reduced risk of COVID-19 death (HR 0.75, 95%CI 0.62-0.92). Living with children aged 12-18 years was associated with a small increased risk of recorded SARS-CoV-2 infection (HR 1.08, 95%CI 1.03-1.13), but not associated with other COVID-19 outcomes. Living with children of any age was also associated with lower risk of dying from non-COVID-19 causes. Among 2,567,671 adults >65 years there was no association between living with children and outcomes related to SARS-CoV-2. We observed no consistent changes in risk following school closure.

Interpretation For adults living with children there is no evidence of an increased risk of severe COVID-19 outcomes. These findings have implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.

Funding This work was supported by the Medical Research Council MR/V015737/1.

Evidence before this study We searched MEDLINE on 19th October 2020 for population-based epidemiological studies comparing the risk of SARS-CoV-2 infection and COVID-19 disease in people living with and without children. We searched for articles published in 2020, with abstracts available, and terms “(children or parents or dependants) AND (COVID or SARS-CoV-2 or coronavirus) AND (rate or hazard or odds or risk), in the title, abstract or keywords. 244 papers were identified for screening but none were relevant. One additional study in preprint was identified on medRxiv and found a reduced risk of hospitalisation for COVID-19 and a positive SARS-CoV-2 infection among adult healthcare workers living with children.

Added value of this study This is the first population-based study to investigate whether the risk of recorded SARS-CoV-2 infection and severe outcomes from COVID-19 differ between adults living in households with and without school-aged children during the UK pandemic. Our findings show that for adults living with children there is no evidence of an increased risk of severe COVID-19 outcomes although there may be a slightly increased risk of recorded SARS-CoV-2 infection for working-age adults living with children aged 12 to 18 years. Working-age adults living with children 0 to 11 years have a lower risk of death from COVID-19 compared to adults living without children, with the effect size being comparable to their lower risk of death from any cause. We observed no consistent changes in risk of recorded SARS-CoV-2 infection and severe outcomes from COVID-19 comparing periods before and after school closure.

Implications of all the available evidence Our results demonstrate no evidence of serious harms from COVID-19 to adults in close contact with children, compared to those living in households without children. This has implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.

 

 

https://www.medrxiv.org/content/10.1101/2020.11.01.20222315v1

Coronavirus T-cell immunity lasts at least six months even when antibodies are undetectable

There was widespread alarmist media coverage in July and again in October of research by Kings College and Imperial College respectively of research showing anti-body reaction to covid19 disappeared within as short as time as a few weeks (average 2-3 months).

Both researchers obliged media by saying the results showed that  controversial ‘herd immunity’ concept could not work.

But a new study by University of Birmingham and Public Health England, shows memory T-cells were present in all 100 asymptomatic non-hospitalised patients they tested, meaning coronavirus patients have cellular immunity for at least six months after infection even when antibodies are undetectable.

It suggests that more people may have had Covid than previously thought but have lost their antibody response, meaning it would not show up in surveillance testing.

Previous studies have shown that Sars – a very similar virus to coronavirus – can induce a T-cell response that lasts 10 years, but it was unknown whether a cellular response also happened in Covid.

Dr Shamez Ladhani, consultant epidemiologist at PHE and the study’s author, said: “Cellular immunity is a complex but potentially very significant piece of the Covid-19 puzzle.

“Early results show that T-cell responses may outlast the initial antibody response, which could have a significant impact on Covid vaccine development and immunity research.”

Professor Paul Moss, the UK Coronavirus Immunology Consortium lead, of the University of Birmingham, said it was the first study in the world “to show robust cellular immunity remains at six months after infection in individuals who experienced either mild/moderate or asymptomatic Covid-19. Six months is an early time point, and cells can live for a very long time.”

Lead ‘ vaccine’ trials not designing actual vaccines

The ‘vaccines’ being prepared for covid19 won’t do what people (and Governments and media) expect of a vaccine.

Peter Doshi, Associate Editor of the BMJ has analysed the lead candidates and concludes:

“None of the trials currently under way are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.”
https://www.bmj.com/content/371/bmj.m4037

The world has bet the farm on vaccines as the solution to the pandemic, but the trials are not focused on answering the questions many might assume they are. Peter Doshi reports As phase III trials of covid-19…
The world has bet the farm on vaccines as the solution to the pandemic, but the trials are not focused on answering the questions many might assume they are. Peter Doshi reports As phase III trials of covid-19 vaccines reach their target enrolments, officials have been trying to project calm. The US…

A devastating critique of the ten worst data failures of Covid19

Data has been the most disappointing factor about humanity’s response to Covid19.

It has been faulty, incomplete, inconsistent, skewed by design, and often, invented (ie. models).

It seems like most of the disputes over how dangerous Covid19 is, and what to do about it, hinge on data that is unreliable. Our ability to interrogate data far outstrips the quality of the data.

It’s not been a flattering picture for the future, of the capabilities of our modern age.
https://www.spectator.co.uk/…/The-ten-worst-Covid-data-fail…

Throughout the pandemic, the government and its scientific advisers have made constant predictions, projections and illustrations regarding the behaviour of Covid-19. Their figures are never revisited as the Covid narrative unfolds, which means we are not given an idea of the error margin….

NZ data – not many tested, not many positives

A sense of perspective on NZ Covid data

(from Jefferies et al. Lancet paper. https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(20)30225-5/fulltext)

Outer circle here is proportional to NZ population, grey is those tested. Blue is those who tested positive. Hospitalised and ICU cases too small to print.

Zeroing on test positive cases (blue circle above, now below), it is not possible from paper to know how many deaths actually went to ICU, so these cells may not be mutually exclusive…

Experts changing their minds as facts against Covid19 mount

Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the Coronavirus Disease 2019 (COVID-19) worldwide pandemic in 2020. In response, most countries in the world implemented lockdowns, restricting their population’s movements, work, education, gatherings, and general activities in attempt to ‘flatten the curve’ of COVID-19 cases. The public health goal of lockdowns was to save the population from COVID-19 cases and deaths, and to prevent overwhelming health care systems with COVID-19 patients. In this narrative review I explain why I changed my mind about supporting lockdowns. First, I explain how the initial modeling predictions induced fear and crowd-effects [i.e., groupthink]. Second, I summarize important information that has emerged relevant to the modeling, including about infection fatality rate, high-risk groups, herd immunity thresholds, and exit strategies. Third, I describe how reality started sinking in, with information on significant collateral damage due to the response to the pandemic, and information placing the number of deaths in context and perspective. Fourth, I present a cost-benefit analysis of the response to COVID-19 that finds lockdowns are far more harmful to public health than COVID-19 can be. I close with some suggestions for moving forward.

https://www.preprints.org/manuscript/202010.0330/v1

Deaths due to lockdown: UK

Thanks to good record keeping and research in the UK that country is now counting the cost of lockdown on health.

The Spectator reports:

A study by the London School of Hygiene and Tropical Medicine found delayed and cancelled breast cancer treatments will cause between 281 and 344 additional deaths. For colorectal cancer, there were an extra 1,445 to 1,563 deaths, lung cancer an additional 1,235 to 1372 deaths and 330 to 342 more oesophagal cancer deaths.

 

A University of Leeds study estimated that there have already been an extra 2,085 deaths from heart disease and stroke as a result of people not accessing timely medical help. A study by the University Hospital of Northern Tees reveals that the number of endoscopies — used to investigate and diagnose bowel cancer — fell to just 12 per cent of their normal level between 24 March and 31 May

 

The National Blood and Transplant Service looked at the period between 23 March and 10 May and found that, compared with the same period in 2019, the number of organ donors fell by 66 per cent and the number of transplants fell by 68 per cent. This year, 87 people died while waiting for an organ transplant, compared with 47 last year.

And in a report by the ONS, an extra 25,472 people have died at home than would otherwise be expected from the average past five years.

Pre-existing immunity is retarding Covid19

Sunetra Gupta talks about her most recent study showing preexisting resistance to Covid19, and that 15-20% sero-positivity in the population could retard Covid19 prevalence and probably already is.

She also refers to some strange behavior of people opposed to looking into these matters.

https://youtu.be/ZCnTtKM6RK8.

Immunity variations explains actual impact of Covid19

Fascinating study shows that removing homogeneity assumptions from population models, and replacing it with variations in virus susceptibility, returns data that better fits the actual impact of Covid19.

The results imply that most of the slowing and reversal of COVID-19 mortality is explained by the build-up of herd immunity.

The estimate of the herd immunity threshold depends on the value specified for the infection fatality ratio (IFR): a value of 0.3% for the IFR gives 15% for the average herd immunity threshold.

Now, compare this to the simplistic exponential models provided to governments across the world, and here in NZ.

https://www.medrxiv.org/conte…/10.1101/2020.09.26.20202267v1