Despite a global effort, an effective vaccine for Covid-19 will be a very long time coming

To get meaningful results from trials, you need significant numbers of people to encounter coronavirus.

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On 21 May, the government announced that a programme of Covid-19 antibody testing will commence in June. This is distinct from the swab tests, which detect, with variable accuracy, whether someone is currently infected. Antibody tests aim to confirm who has had Covid-19 in the past, including those who had minor or no symptoms.

Initially, antibody tests will be offered to health and care workers, but clinicians will also be able to order them for appropriate patients. On the face of it, this sounds like good news. Indeed, Matt Hancock resurrected the prospect of coronavirus “passports”, issued to those proven by antibody testing to have previously had the infection – the idea being that a “passport” would allow them return to normal life as they are supposedly no longer susceptible.

The history of antibody testing has been chequered. In early April, the government ordered 17.5 million kits that proved so unreliable as to be useless. Covid-19 is only one of a number of coronaviruses (the others cause the common cold) and early tests were dogged by cross-reactivity from antibodies against these viral cousins – as well as, intriguingly, failure to detect Covid-19 antibodies in some patients definitely known to have recovered from the disease. 

The antibody test now being rolled out performs substantially better, with reported accuracy of close to 100 per cent. In order to achieve this, however, the test focuses on antibodies against proteins contained deep within the virus’s core – proteins that appear specific to this particular coronavirus, but which have nothing to do with its ability to infect cells. Core proteins only become “visible” to the immune system – and hence only provoke antibody production – once viral particles have been broken up during an established infection. While these core antibodies give a reliable signature that “Covid-19 was here”, they tell us nothing about the tested individual’s immunity – their ability to repel repeat infection.

The antibodies that might prevent Covid-19 causing infection are those that attack proteins in the virus’s outer coating, most importantly the “spike” or S-protein – the molecule that acts as a key and unlocks entry into human cells. The bulk of vaccine initiatives being pursued around the world aim to find ways to stimulate the immune system to produce S-protein antibodies; the idea being that when trying to infect a vaccinated individual, Covid-19 would encounter a sea of pre-formed antibodies that would bind to its key and render it ineffective.

These “neutralising” antibodies illustrate some of the complexity of the race to achieve an effective vaccine. Results from an animal study of one S-protein vaccine candidate suggest that it doesn’t prevent infection, though it may reduce the chance of Covid-19 causing pneumonia. Were that to be borne out in human trials, it may still be a worthwhile outcome – viral pneumonia appears to be the gateway into the severest form of the disease – but there are many unknowns. The life-threatening complications of Covid-19 are not generally a direct result of viral infection itself, but arise from an uncontrolled immune response characterised by huge inflammation. This typically appears after six to ten days, when antibody production is starting to kick in, raising the possibility that in some people antibody-mediated immunity may actually be harmful. How a vaccine that primes antibody production against Covid-19 will affect susceptibility to this inflammatory syndrome is unknown.

Other facets of the immune system may be vital in containing and eliminating Covid-19 while it is still a trivial infection. Certain T-lymphocytes, a sub-class of immune cell, are able to recognise and destroy cells infected with a wide range of viruses. This innate immune response fights viral infection before antibody production even begins, and may be the explanation why children – whose innate immunity is constantly stimulated by viral illnesses – appear more resistant to Covid-19. Weakened innate immunity may be at the heart of severe disease.

The only way of assessing whether vaccine-induced antibodies are helpful or harmful will be to track outcomes in volunteers divided into two random groups: one group given doses of the new vaccine, the other given a placebo. To get meaningful results, you would need significant numbers of people in each group to encounter coronavirus and see what happens. But the success of lockdown creates a paradoxical problem. Rates of new infection are currently low, so relying on participants to encounter Covid-19 naturally will mean trials will take a very long time to gather sufficient data.

One solution would be to turn these studies into “challenge” trials: deliberately exposing volunteers to live coronavirus. The World Health Organisation has cautiously endorsed this approach on grounds of the greater good: a vaccine is vital. It advises that volunteers should exclusively be fit young adults, the demographic least likely to suffer severe Covid-19. Such trials still wouldn’t provide information about how those most vulnerable would fare. And, even among fit young adults some volunteers may die.

Challenge trials may be ethically more acceptable were there an effective treatment with which to rescue volunteers who become seriously unwell. We are a long way from that. Trump’s much-vaunted hydroxychloroquine and azithromycin have now been shown to increase deaths among hospitalised patients. Repurposed antiviral drugs achieve at best marginal benefits. The global medical-scientific community is grappling with a complex new disease. Economic imperatives demand fast solutions. Biological reality suggests we are going to need to suppress and contain Covid-19 for a good while yet, to allow our understanding to grow.

Phil Whitaker is a GP and writes the New Statesman’s “Health Matters” column. His books include Chicken Unga Fever: Stories from the Medical Frontline (Salt)

This article appears in the 29 May 2020 issue of the New Statesman, The peak

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