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Let’s Prioritise COVID-19 Vaccines for Antibody-Negative High-Risk Individuals

Let’s Prioritise COVID-19 Vaccines for Antibody-Negative High-Risk Individuals

A woman passenger in PPE waits for a train in New Delhi, November 2020. Photo: PTI/Kamal Kishore.

The whole world is eagerly waiting to receive its first dose of a COVID-19 vaccine. Governments, politicians, and the people are all equally concerned about the implications of the pandemic at the individual and community levels, and its healthcare and economic implications. We expect a vaccine to miraculously alleviate the severity of the pandemic – but this is likely to happen only to an extent.

Should we vaccinate all 1.35 billion Indians and in fact the 7.7 billion global citizens? It may take at least two or three years to do so, due to the short vaccine supply and logistical issues. So most countries are planning to vaccinate their high-risk populations first and the rest later, when enough doses will be available. India, in the first stage, plans to vaccinate 250 million citizens who are in its high-risk list. This strategy is indeed a good one.

Individuals who have recovered from the disease, whether symptomatic or not, are immune to reinfection for a certain period. The reports of reinfection are still relatively rare.

Since January this year, more than 60 million individuals have contracted the virus and 40 million have already recovered.

Researchers are still working out the exact mechanism of immunity and the relative contribution of antibodies and cell-mediated immunity. But we are indeed confident of one thing: this far, there hasn’t been a significant challenge of en-masse reinfection. Currently, some 11 months after the emergence of SARS-CoV-2, more than 99% of the 40 million individuals who have recovered from COVID-19 have not reported a second episode of infection.

The existing body of evidence suggests the antibody response after a COVID-19 infection is reliable and sustained. Due to the inevitable shortages in the supply of COVID-19 vaccines, we must prioritise high-risk groups.

We can streamline the process further if we vaccinate the COVID-19 antibody-negative high-risk individuals first and then the positive antibody individuals. We can also offer antibody tests free of cost.

Second, we can also request those citizens who are antibody-positive to opt out of being in the priority list and receive their doses once the antibody-negative high-risk individuals have all been vaccinated. The political leaders of various countries can appeal to their citizens along these lines.

A COVID-19 vaccine, like any other drug or vaccine, is not expected to be 100% safe. Mild adverse events could be very common, moderate ones not uncommon and severe ones not rare. Considering the risks of contracting a severe COVID-19 infection and the aftereffects, such as ‘long COVID’, it is perfectly sensible and essential to get vaccinated.

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Why should those who are already recovered from the disease and hence immune from reinfection receive the vaccine, when they are still antibody-positive? The earlier stories of waning antibody titres do not hold good any more. There is plenty of published high-quality data on the sustained and robust immune response after infection.2

The earlier reports of rapidly waning antibody titres could have been a manifestation of the intermediate contraction phenomenon, whereby the antibody titres demonstrate a fall after the initial peak, but stabilise later.2 A more recent study revealed that the anti-Spike-protein IgG antibody was relatively stable over more than six months. Spike-specific memory B cells, responsible for the production of antibodies against the novel coronavirus’s spike protein, were more abundant at six months than they were at one month. The reportedly low titres in some studies could also be due to methodological issues.3

More than 90% of seroconverters have detectable neutralising antibody responses.2 The vast majority of positive individuals have moderate-to-high titres of anti-spike-protein antibodies. Those individuals who are antibody-negative after a natural infection have strong cell-mediated immunity, protecting them from a severe disease if reinfected.

Unfortunately, testing for cell-mediated immunity needs sophisticated laboratories and are not suitable for public-health interventions. We have absolutely no data on any additional protection a vaccine can provide in those who are already antibody-positive. No COVID-19 vaccine trials have enrolled antibody-positive individuals to assess the immune response, extra protection and safety profile.

The earlier argument, of the unreliability of antibody testing with high false negativity and false positivity, also does not hold right now. The COVID-19 antibody-testing method and data is now far more developed than it used to be at the beginning of the pandemic. ELISA antibody kits with very high sensitivity and specificity are now available. All vaccine trials are testing recruits for antibodies before enrolment and after administration of the vaccine. If antibody testing is considered reliable in vaccine trials, why can’t we believe the same testing is reliable on the ground?

The novel coronavirus virus is unlikely to disappear from the face of Earth, ever. The virus is well-adapted to human transmission, so the pandemic will turn into an endemic, and occasional flare up into epidemic proportions. We need a vaccine for the faster control of the pandemic and to prevent epidemics after that.

There is no doubt that antibodies to COVID-19 or even cell-mediated immunity is unlikely to last a lifetime. The antibody in already positive individuals will indeed wane in time. Hence, antibody-positive individuals will require vaccination at a later stage. But there may not be a need to vaccinate antibody-positive individuals when they currently have antibodies to the novel coronavirus.

How practical and cost-effective is it to perform antibody tests for the entire population? The process will incur additional resources and logistics, of course, but mass-testing could be far more cost-effective than vaccinating antibody-positive individuals, provided we identify areas where the strategy will work out best.

The existing seroprevalence data can guide us in selecting regions where prevalence is already high. Many metropolitan cities in India have indeed reported very high seroprevalence. Antibody tests before vaccination will be practical and cost-effective in these regions.

At the same time, the strategy may not be so cost-effective in places that have reported a low seroprevalence. Collecting seroprevalence data in all areas can guide us as to where a selective vaccination strategy might work better. For example, a non-trivial fraction of healthcare workers could already be antibody-positive, and so we can prioritise the COVID-19 vaccine for antibody-negative healthcare workers.

In sum: let us vaccinate our antibody-negative high-risk population first. We can simultaneously generate data on the usefulness of the vaccine in individuals who are already immune. We need to utilise our precious resources wisely.

Dr Abdul Ghafur is a consultant in infectious diseases, Apollo Hospital, Chennai.

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