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

Children in more danger from lockdown than Covid19

“…benefits [of lockdown], however, are overshadowed by the negative consequences of the lockdown. First and foremost is the direct impact on their health. Emergency departments in the UK experienced unprecedented reductions of >50% in attendances during lockdown. [8] In Scotland, children’s emergency department attendances fell proportionally more than any other age-group.  This raises concerns that children with critical illnesses were not accessing health services on time and, therefore, suffering potentially avoidable harm.

 

60% of paediatricians responded within 7 days and, and 241 (32%) of 752 emergency department paediatricians had witnessed delayed presentations. Free text responses revealed diabetes mellitus (new diagnosis/diabetic ketoacidosis) as by far the most common delayed presentation, followed by delayed presentations of sepsis and new cancer diagnoses.

 

There were also nine deaths, resulting mainly from sepsis and malignancy, where delayed presentation was considered by the reporting paediatrician to be a significant contributing factor – higher than the total number of childhood covid-19 deaths reported over the same period in England.

Lockdown measures reduced the risk of covid-19, but had unintended consequences for children

Sunetra Gupta on unprofessional conduct of pro-lockdown scientists

Sunetra Gupta, founding signatory of the Great Barrington Declaration, wrote for the Daily Mail. Here is an edited set of excerpts.

I was utterly unprepared for the onslaught of insults, personal criticism, intimidation and threats that met our proposal. The level of vitriol and hostility, not just from members of the public online but from journalists and academics, has horrified me.

… Covid-19 is not a political phenomenon. It is a public health issue — indeed, it is one so serious that the response to it has already led to a humanitarian crisis. So I have been aghast to see a political rift open up, with outright abuse meted out to those who, like me, question the orthodoxy.

That is why I have found it so frustrating how, in recent weeks, proponents of lockdown policies have seemed intent on shutting down debate rather than promoting reasoned discussion.

 

It is perplexing to me that so many refuse even to consider the potential benefits of allowing non-vulnerable citizens, such as the young, to go about their lives and risk infection, when in doing so they would build up herd immunity and thereby protect the lives of vulnerable citizens.

 

Yet rather than engage in serious, rational discussion with us, our critics have dismissed our ideas as ‘pixie dust’ and ‘wishful thinking’.

This refusal to cherish the value of the scientific method strikes at the heart of everything I, as a scientist, hold dear. To me, the reasoned exchange of ideas is the basis of civilised society.

 

So I was left stunned after being invited on to a mid-morning radio programme recently, only for a producer to warn me minutes before we went on air that I was not to mention the Great Barrington Declaration. The producer repeated the warning and indicated that this was an instruction from a senior broadcasting executive.

I demanded an explanation and, with seconds to go, was told that the public wouldn’t be familiar with the meaning of the phrase ‘Great Barrington Declaration’.

 

And this was not an isolated experience. A few days later, another national radio station approached my office to set up an interview, then withdrew the invitation. They felt, on reflection, that giving airtime to me would ‘not be in the national interest’.

 

But the Great Barrington Declaration represents a heartfelt attempt by a group of academics with decades of experience in this field to limit the harm of lockdown. I cannot conceive how anyone can construe this as ‘against the national interest’.

 

Moreover, matters certainly are not helped by outlets such as The Guardian, which has repeatedly published opinion pieces making factually incorrect and scientifically flawed statements, as well as borderline defamatory comments about me, while refusing to give our side of the debate an opportunity to present our view.

 

I am surprised, given the importance of the issues at stake — not least the principle of fair, balanced journalism — that The Guardian would not want to present all the evidence to its readers. After all, how else are we to encourage proper, frank debate about the science?

 

On social media, meanwhile, much of the discourse has lacked any decorum whatsoever.

 

I have all but stopped using Twitter, but I am aware that a number of academics have taken to using it to make personal attacks on my character, while my work is dismissed as ‘pseudo- science’. Depressingly, our critics have also taken to ridiculing the Great Barrington Declaration as ‘fringe’ and ‘dangerous’.

 

But ‘fringe’ is a ridiculous word, implying that only mainstream science matters. If that were the case, science would stagnate. And dismissing us as ‘dangerous’ is equally unhelpful, not least because it is an inflammatory, emotional term charged with implications of irresponsibility. When it is hurled around by people with influence, it becomes toxic.

 

But this pandemic is an international crisis. To shut down the discussion with abuse and smears — that is truly dangerous.

Yet of all the criticisms flung at us, the one I find most upsetting is the accusation that we are indulging in ‘policy-based evidence-making’ — in other words, drumming up facts to fit our ideological agenda.

 

I have been accused of not having the right expertise, of being a ‘theoretical’ epidemiologist with her head in the clouds. In fact, within my research group, we have a thriving laboratory that was one of the first to develop an antibody test for the coronavirus.

Clearly, none of us anticipated such a vitriolic response.

 

The abuse that has followed has been nothing short of shameful.

But rest assured. Whatever they throw at us, it won’t do anything to sway me — or my colleagues — from the principles that sit behind what we wrote.

Professor Sunetra Gupta is an infectious disease epidemiologist and a professor of theoretical epidemiology at the Department of Zoology, University of Oxford.

https://www.dailymail.co.uk/debate/article-8899277/Professor-Sunetra-Gupta-reveals-crisis-ruthlessly-weaponised.html

Elimination proponent admits it means no return to normal

An early proponent of New Zealand’s elimination strategy has now admitted that the approach means the country cannot go back to normal.
In early interviews Souxsie Wiles claimed to be “excited” about vaccines for Covid19, but now says the early ones are unlikely to prevent death or transmission (see BMJ assessment of lead vaccines).
Wiles she says this is particularly problematic for New Zealand because it “stamped out” Covid19. A partially effective vaccine would not allow us to open borders and go back to normal (we presume she means that covid19 would re-enter the country and/or resume transmission).
Wiles has therefore clarified that it is New Zealand’s strategy which means New Zealand can not go back to normal.
This will be surprising and unpleasant news to most citizens. Wiles embraced the strategy and the government’s plan to eliminate and wait for a vaccine.
This is precisely the dilemma that Covid Plan B predicted would happen, and why we opposed the elimination and lockdown strategy.
We said that if elimination was the goal, our quandary was that we could not have a situation where covid19 was in transmission. Which meant we had to wait until a totally effective vaccine was available. We doubted that such a vaccine would be ready even in 2021.
In her Stuff article, Wiles seems to be happy with the idea that this isolation is the new normal. We are not.
 

How have dire predictions for Sweden panned out?

An article in the NZ Herald on May 27, 2020 predicted Sweden would have 56,000 more COVID-19 deaths and had made “a fatal mistake”. At the time of publishing Sweden had experienced 4408 deaths.

So, how’s that prediction looking five months on?

It was wrong. The deaths have not been 56,000, but as at 23 October, 5,933.

In the past five months a further 1525 people sadly died.

Daily deaths plateaued in July, and over the following three months (23 July to 23 i.e., 92 days) 202 people – an average of just over 2 a day – have died. To put that into perspective, ca. 246 people die every day in Sweden; 77 from cardiovascular disease (Sweden’s biggest killer).

Despite an upsurge in cases (starting ca. 4th September) that now matches the peak of cases recorded in June 2020,  the average daily death since 4 September has been 1.8 deaths per day. Over the last seven days, (16 to 23 October) the daily death rate was 0.57.

Data taken from:

https://ourworldindata.org/coronavirus/country/sweden?country=~SWE

https://www.statista.com/statistics/525353/sweden-number-of-deaths/

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

Call for data on Covid-19 health impacts

22 October 2020

New Zealand has not released any analysis about the negative health impacts of the Covid-19 elimination and lockdown policy.

This is highlighted by studies released in the UK this week which indicates that their lockdowns are responsible for thousands of deaths and new illnesses, principally as a result of delayed cancer diagnoses (see note below).

The only known study of lockdown health impacts in New Zealand was of a Dunedin primary health clinic, where referrals and tests had dropped 100% and 99% respectively. Anecdotal evidence provided to the Covid Plan B group is that referrals and tests may be down across the country by two thirds. Auckland District Health Board is also investigating after four women died during and after pregnancy this year, with three dying since alert level 3 was instituted in late March. Expected numbers of deaths are between 0 and one from previous years.

Evidence provided from affected individuals indicate illnesses and health prognosis have worsened due to delayed tests and treatment. Whether these cases represent a wider problem is not known.

Dr Simon Thornley, spokesman for Covid Plan B, said the Government’s elimination and lockdown policy was based on hope, because little analysis of the downsides of the policy has been carried out.

“If you base your rationale on discredited models and you don’t count impacts, this is not a policy based on evidence.

“This is a policy based on an assumption that the low Covid-19 impact is the result of the lockdown policy. There is no proof of that, and international studies indicate it is unlikely.

“This is also a policy continued on the assumption that there are no negative effects. But firsthand testimony in New Zealand and overseas statistics suggest this is not true. Economic analysis from the government and independent sources indicate that lockdowns are a disproportionate response to Covid-19. The effect on unemployment is now clear, with a 38% rise in adults on the jobseeker benefit since late March. Now, the impact of delayed diagnosis and under treatment of other conditions must be considered.

“We are not even trying to count what the other effects have been on health. We do not know how many people have died, had conditions or prognosis worsen because of the ways lockdown and fear have affected healthcare.

“We call on the Ministry of Health to undertake the same studies we’ve seen in the UK, and to weigh those costs against what they imagine, or count, are the benefits of the elimination strategy,” Simon Thornley says.

– ends

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.