Test, treat, isolate and support
Mohsen Shahmanesh examines the effectiveness, safety and likely take-up of the Covid vaccines
So we now have a vaccine against Covid-19. To be exact, in the UK we have one approved vaccine, two more ready for submission for approval and many more in the pipeline.
We are clearly entering a new era. But can we talk of a post-Covid era? Let us demystify the mystique surrounding this moment. What do the vaccines do? What do the figures bandied about mean? What do we mean by herd immunity? And, finally, where are we with ‘test and trace’, and Boris Johnson’s magic ‘moonshot’?
Currently more than 170 different vaccines are being developed across the world, with 12 in the final, phase 3 stage.1 Before I discuss the different mechanisms of creating a vaccine, we need to understand that there is a difference between being infected and being ill with that infection. That is because infection and illness are not necessarily the same thing and in fact the majority of people infected with Covid-19 have no symptoms. This is true of most infections. Virtually all of us become infected with human papilloma virus (which causes warts and some cancers) through our life, but only a minority will have visible warts or develop cancer of the cervix and mouth. All the vaccines for Covid-19 that are being tested across the world, to my knowledge, have as their end-point the prevention of the Covid disease and not whether the person vaccinated can become infected or not. In other words, we cannot know whether the vaccines will prevent the spread of the virus in the community. This is an important point to understand when we think about herd immunity - more on that later.
The aim of all vaccines is to offer a part of the virus - usually a section on its outer surface - that the immune system can recognise and mobilise against. In the case of Covid-19, this is the spike protein, which is the key allowing the virus to lock onto the susceptible cell, enter it and hijack its reproductive machinery in order to make millions of copies of itself. There are four major ways of inducing an immune response to a pathogen. Three of them use technologies that have been employed in the manufacture of other vaccines. The fourth is a new, and exciting, technology:
- Inactivated virus: Here the mechanism for reproduction of Covid-19 is inactivated rendering it harmless. Vaccines in phase-3 development are all from China: Valneva Sinovac Biotech, Sinopharm and China National Biotec Group (CNBG). The UK has pre-purchased 60 million doses of the Valneva vaccine, with the option of another 40 million doses.2
- Adenovirus vaccines: The Covid-19 spike protein is linked to a non-replicating, harmless virus. Examples are the ‘Oxford’ AstraZeneca vaccine (where a monkey adenovirus which does not infect humans is used as the adjuvant) and the Jensen vaccine. China is currently vaccinating its army with its CanSino Biologics3 vaccine, even though the phase 3 trials are incomplete. The Russian Sputnik V vaccine belongs to this category and is being rolled out - again before phase-3 trials have been completed. The UK has bought 100 million doses of the ‘Oxford’ vaccine.
- Protein adjuvant: The Covid-19 spike protein is presented to the body in association with an inert protein as an adjuvant. Vaccines in development are the GSK/Sanofi Pasteur and Novavax. The UK had purchased in advance 60 million doses of each.
- Messenger RNA (mRNA). This is a totally novel approach, where the mRNA that normally codes for the Covid-19 spike protein is synthesised in the laboratory. When injected into the body, the mRNA will produce the spike protein, which is then recognised by the body’s immune system as an intruder and will stimulate an immune response. Both the Pfizer/BioNTech and Moderna vaccines are made in this way. The advantage of this technology is that it is entirely synthesised in the laboratory - quick to develop and easy to scale up. The disadvantage at present is the fragility of the product at room temperature - needing deep refrigeration and cold chain - keeping it cold at all times. The UK has ordered 40 million doses, and the Medicines and Healthcare products Regulatory Agency has approved the Pfizer/BioNTech vaccine for general use.
The numbers currently being quoted for the efficacy of the three vaccines that have completed phase-3 trials should be understood with two provisos. Firstly the effectiveness figures reported (90%-95%) will almost certainly be lower, once they are rolled out. But they still remain impressive, when we consider that the flu vaccine is only 50% effective in preventing influenza (the disease). Secondly, as mentioned we do not know if they prevent infection. But the results show that they are safe to use, with only minor side effects.
Some people are freaked by long-term side effects but I know of no other vaccine that produces long-term effects - the MMR scare having been clearly shown to be based on defective science. The issue of cold storage (-70C in the case of the Pfizer vaccine) also makes it difficult to roll out even in advanced industrial countries, and near impossible in other settings.
The truly disgusting scramble by various states to buy out whatever vaccine is in the process of being produced, in total disregard of the fact that Covid-19 does not recognise frontiers, was predictable. Thus a campaign to force rich nations and big pharma to contribute to the global pool of vaccine and fund its distribution is vital for the left and other progressive forces. What has also emerged is the affect on the poor and disadvantaged - which in the west to a great extent translates as predominantly ethnic minorities. This too will require focus by the left. Thus even within these hoarding states the issue of the equitable use of the initially limited vaccine availability should form a central platform for the left.
What has been striking on the international scale is the close collaboration between scientists regardless of nationality - contrasting sharply with the nationalist clamour for the spoils of their endeavours. Currently, under the umbrella of the World Health Organisation, the Vaccine Alliance (Gavi) and the Coalition for Epidemic Preparedness Innovations (Cepi) have formed the Covax facility to supervise the equitable distribution of the various vaccines that come into the market in countries that do not have access to them. Currently Covax is grossly underfunded, only having received $2 billion of the $7 billion it estimates will be required. Yet without a global vaccination effort, like the one that led to the total eradication of smallpox and the near total eradication of polio, Covid-19 will continue on its devastating course.
And then there is the cost. Some of the producers, such as AstraZeneka, have undertaken to sell at cost price (though the details of how that price is determined remain unclear). Glaxo and Sanofi has also claimed it will not make a profit from the vaccine and have pledged 200,000 doses to Covax - a drop in the ocean. Others - and significantly the mRNA vaccines now on the market (Pfizer/BioNTech, Modena) - have made no such undertaking. There are, after all, bucketfuls of money to be made in this bear market. Meanwhile China, with four vaccines in phase-3 trials, has been embarking on systematic “vaccine diplomacy”, rolling out its trials in at least 16 countries and promising them early access to the vaccine if successful, and even the technological knowhow to manufacture them locally.4
We cannot leave this discussion without mentioning the voices raised against the vaccines. Social media is being saturated by an avalanche of disinformation. Sadly this wave is impervious to facts and evidence, but here goes. Short-term side effects from the vaccines given to several hundred thousand volunteers are no more than you would expect: a sore injection site and a day or two of mild flu-like illness. As for long-term complications, it is too early to say what they might be, but I do not know of any vaccine in the entire history of mass vaccination that has actually caused long-term side effects. Nor would I expect one, other than those caused by the occasional bad batch as a result of some manufacturing defect or contamination - as can occur with any drug.
The MMR vaccine scare has been conclusively shown to be faulty, if not fraudulent. I know the anti-vaccine crowd will take no heed of facts, in the same way that the HIV deniers once ignored science. In South Africa, for example, ex-president Thabo Mbeki’s denial that HIV caused Aids resulted in the death of over 300,000 people.5 Their blood is on his hands - as the blood of millions who may be misled will be on the hands of the fact-deniers in today’s pandemic.
The debate around herd immunity has truly entered the realm of the absurd. So let us just look at the facts. There is, to my knowledge, no known case of any pathogen - whether bacterial, viral or protozoal - causing natural herd immunity that eradicates disease. Before vaccination came along, almost all children would get measles and mumps. The few adults who miraculously missed getting the infection as a child would catch it in later years - in a more serious form. Until we had anti-tuberculosis treatment TB was rife within populations, with no evidence of herd immunity, as was (and is) malaria. Scarlet fever died out not because of herd immunity, but because of the availability of antibiotics.
A low degree of population immunity did exist against common infections, as shown by the devastating effect of introducing these pathogens to populations never exposed to them (native Americans, for example), but this low-level immunity was not enough to stop the infections spreading in those communities too, albeit in a less explosive form. So I do not know where the Swedish public health authorities went to university to come up with what is clearly a failing policy (which they are now quietly shelving).
What is undoubtedly true is that after mass immunisation with some vaccines, herd immunity can stop the spread of the infection to the minority who had not been vaccinated. The proportion of people needed to be vaccinated to convey this form of herd immunity depends on the efficacy of the vaccine and whether it prevents infection - as well as the disease, on the one hand, and the infectivity of the organism on the other. In the case of measles, which is very infectious, herd immunity is achieved when upwards of 80% of the population are vaccinated.
If the current 90% or greater efficacy of the Covid-19 vaccines in preventing disease remains valid for preventing infection, then we would expect herd immunity after vaccinating about two thirds of the population.
Test and trace
A lot has been written about the sham of the UK government’s ‘test and trace’ programme. Suffice to say, it was needlessly expensive (about £12 billion); completely wasteful; peppered with cronyism; ineffective (incompetent companies subcontracting to other equally incompetent companies); absurdly centralised - when we already had a ready-made NHS local public health network, trained for this very thing and proven superbly efficient at delivering local public health at a fraction of the cost. And it missed out the two other critical aspects of ‘test and trace’, namely ‘isolate and support’ - TTIS.
Now the Johnson administration is rolling out another totally wasteful mass screening of the general population, using lateral flow test kits - the so-called ‘moonshot’. The government has just spent £500 million on the Innova lateral flow test (used in Liverpool). These are easy to do, quick, not exorbitantly expensive and with a sensitivity of about 80% in laboratory conditions, although this figure falls to 58%, when done by self-trained members of the public - the very people who are meant to use this test kit. In other words, 20%-40% of those infected will be missed. What about falsely labelling those that are not infected - the false positives? On the face of it the rate of false positives appears low (0.3% of all those tested) and looks reasonable. That is, until you translate that into what happens in real life.
In a recent BMJ article Jon Deeks, professor of biostatistics at Birmingham University, made an interesting calculation. If 100,000 people are tested in a city where the prevalence of Covid-19 is 400 per 100,000 (a figure slightly lower than Manchester in November), then, using a sensitivity of 58%, this test will give us 630 positive cases.6 But of these 630 only 230 will have the infection and the other 400 will be labelled as infected when in fact they are not - ie, false positives! So moonshot screening, as it stands, will miss the moon by a factor of nearly 2 to 1. It is clearly unsuitable for population testing in the government’s Test and Release scheme, though it might be useful in screening individual visitors to, say, care homes and in testing care staff. The government recently advertised a contract for £912 million to deliver rapid testing across the country - which would be better used to improve the dismal Test, Trace, Isolate, Support programme.7
There is no substitute for a proper lockdown, followed by a scheme to test, treat, isolate and support those that get infected. This must be linked to a systematic, equitable vaccination programme, based on vulnerability and need, rather than income and status. And, of course, this must be a global policy.
Reuters Health News, June 2020.↩︎
P Chigwedere, GR Seage, S Gruskin, TH Lee, M Essex. ‘Estimating the lost benefits of antiretroviral drug use in South Africa Journal of Acquired Immune Deficiency Syndromes October 2008, pp410-15.↩︎