No mortality difference between Sweden and Norway, but Norway result came at huge cost

An important study (preprint at time of this post) shows similar mortality rates in Sweden and Norway despite different national responses to the Covid19 virus. But critically, Sweden’s mortality outcome came at a much cheaper economic cost.
Despite an order of magnitude difference in case-fatality rates in Sweden (higher) compared to Norway, the two countries had very similar overall mortality profiles.
There was a big difference though in national costs. Norway’s more restrictive policies resulting in public spending 2.6-fold more than Sweden (Norway: 4,176 Euros per person & Sweden 1,580 per person) during the epidemic.
It also reveals that the spike in mortality in Sweden which had caused consternation, and some unfortunate glee among pro-lockdown observers, was most likely due to ‘displaced mortality’ from low mortality in earlier seasons. Norway had no overall mortality spike.

Lead vaccines: answers needed

As lead vaccines announce good results and intentions to register for fast-tracked safety authorisation in EU and the US, immunologist Byram Bridle, reminds us of questions that they will need to answer:

Dr. Byram Bridle, PhD, Associate Professor of Viral Immunology, University of Guelph, Ontario, Canada

  1. How many of the total study subjects are being reported on? Partial results can range from being representative of the entire data set to being biased.
  2. How many study subjects had detectable immune responses and what was the magnitude?
  3. Were there antibody responses in the respiratory tract, which is where SARS-CoV-2 infects, and did these antibodies efficiently neutralize the virus?
  4. Were SARS-CoV-2-specific T cells induced? A balanced anti-viral response should include antibodies to prevent infection and T cells to kill viruses that get past the antibody barrier.
  5. Did the immune responses have a ‘Th1’ or ‘Th2’ bias? The former type of immune response is optimal against viruses, the latter is usually sub-optimal and sometimes even dangerous in the context of respiratory viral infections.
  6. Did the vaccine confer long-term immunological memory? A prophylactic vaccine may be useless without this. If immunological memory is short-lived, vaccinated individuals could become susceptible to infection before enough people are immunized to achieve ‘herd immunity’. Another term for this is ‘duration of immunity’ (i.e. how long does immunological protection last?)
  7. How did the vaccine perform in senescent animals and/or elderly humans? Those most in need of protection against COVID-19 are the elderly and immunocompromised.
  8. How was safety assessed and what were the results?
  9. Have the results been published for review by other scientists? If not, when? It is recommended to publish in open-access journals, which are available to the public. Comments merely reflect opinions unless there are validated data to back them up.
  10. Related to #6 above, what is the plan to manufacture and roll-out enough vaccine doses to achieve herd immunity in any given country? What is the realistic timeline for this? If >1 year, there is no way to know if COVID-19 vaccines will confer protection for this long because they didn’t exist one year ago. The development of every historical vaccine took >4 years, so there were years-worth of ‘duration of immunity’ data. For example, optimistic projections suggest ~1 billion doses might be possible by the end of 2021, but for two-dose regimens, that means only 500 million people could potentially be vaccinated in just over one year. With the global population at 7.8 billion people, that represents only 6% of the world’s population. The lowest estimate to achieve herd immunity is 60%.
  11. How will equitable distribution of vaccines be accomplished? For example, pre-order waiting lists seem to be dominated by developed countries; are any developing countries on these waiting lists?
  12. What is the cost of a full vaccine regimen going to be? Is it affordable for developing countries? Some epidemiologists have predicted that efficient roll-out of vaccines to developing countries will require the price to be <$6 US.
  13. Storage conditions for vaccines could impact distribution and market competitiveness. What data are available to support the claimed storage conditions? For example, the default storage temperature for RNA in research laboratories is -80o This is based on a plethora of scientific evidence that RNA is more stable at this temperature compared to -20oC.

Danish mask study result; no statistical difference from not wearing one

Only two days after the NZ government announced mandatory mask wearing rules the much awaited Danish mask study was published, and it is conclusive; masks give no statistically significant protection from Covid19.

Here’s the study: https://www.acpjournals.org/doi/10.7326/M20-6817

Results:

A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was −0.3 percentage point (95% CI, −1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection.

Conclusion:

The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection.

Below is our Euler diagram summarising the findings of the Danish mask trial.

The small difference in event proportions, with a slightly higher proportion in the control group, was not distinguishable from a chance finding (“not statistically significant” is the boffin term).

This is probably the best evidence we have up to now, which is disappointing for advocates of mask use to prevent covid-19 infection. This evidence is consistent with previous trials which found no effect in trials designed to assess the effect of masks to prevent the community transmission of influenza.

That time when no one noticed Covid19

A study shows a ‘peak’ of Covid19 cases in Italy in September 2019, and no one had noticed.

This hints that Covid19 was circulating even earlier, as the study used blood samples from a lung cancer patient screening trial that had begun in September 2019.

This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic.

https://journals.sagepub.com/doi/10.1177/0300891620974755

Survey: Life in lockdown for NZ kids

A banal report from the Children’s Commissioner about life in lockdown for NZ kids has a few interesting findings when you dig into it.

By and large, it appears that our kids dealt reasonably resiliently with what the report stupidly claims to be “unprecedented times”

From their survey, half of kids’ parents worked at home and half went out to work – that’s a lot different from the “work from home” message that dominated the perspective of the Government.

Only 8% of kids list the public health messages as a memorable feature of the period.

The absolutely dominant feature and commonality among all kids is that they really missed and disliked the physical separation from their friends, particularly via school. That speaks to a reality of the lives of almost all of us – and something denied by lockdown and social distancing: we simply cannot live for very long separated from each other.

LifeinLockdown-OCC-Nov2020

 

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….