Issue #106: Booster vaccine shots, staying out of hospital with Omicron and Long COVID

Written by Nobel Laureate Professor Peter Doherty

The question many of us are no doubt asking is: how well is vaccination protecting us against the development of Long COVID (LC) following infection with the currently circulating Omicron BA.1 and BA.2 variants? Unfortunately, it’s too early to answer that, though there is some evidence that vaccination can, for a time at least, lessen the likelihood that we will be infected with SARS-CoV-2. Obviously, if we don’t catch the infection, we won’t develop LC.

We can be reasonably confident that taking that additional third or fourth ‘booster’ shot will help us to avoid the severest, acute manifestations of COVID-19. For Omicron BA.1, three vaccine doses can, at least for a time, be about 80% effective at keeping those testing positive out of hospital. This should substantially protect us against what I think of as Post COVID, the debility that results from permanent organ damage that can occur if we become very ill and require, for example, an ICU stay. As things stand, that ‘Post COVID’ effect is included under the LC classification.

Last week (#105), we looked at the tentative conclusion from UK National Health Service (NHS) data that 8-9% of triple-vaccinated people are developing some LC symptoms detected four to eight weeks after they returned a positive PCR test result.

As there are now so few unvaccinated, or previously uninfected, people anywhere on the planet, there’s no ‘zero’ baseline for determining vaccine efficacy. But the comparison can be made for subjects who received two vaccine doses, then did, or did not, get the additional ‘booster’ shot(s).

A massive study done in the US between February 14 and March 27, 2022, in nursing home residents, a very vulnerable population, compared COVID-19 incidence in subjects who had two doses of the Pfizer or Moderna mRNA vaccines, or a single dose of the adenovirus-vectored (like AstraZeneca) Jansen vaccine, with those who recently received an additional shot of an mRNA vaccine at least 14 days previously. At that time, the US was largely experiencing Omicron BA.1 infection. The conclusion was that the booster dose reduced the likelihood of catching the infection by about half, which is clearly a very significant effect in this type of community setting.

A separate study involving more than two million people in Qatar who had two versus three doses of one or other mRNA vaccine for protective efficacy against the Omicron BA.1 variants came to surprisingly similar conclusions. Here, the cumulative incidence of symptomatic infection by 35 days of follow-up was 2.4% in the three-dose cohort versus 4.5% in the two-dose recipients, while effectiveness against hospitalisation or death was 76.5% in favour of those who had been boosted.

A further Israeli study (published in April 2022) in health care workers who were given a third (August/September 2021) or a fourth (January 2022) dose of the Pfizer mRNA vaccine found that breakthrough infection rates for Omicron were 19.8% and 6.9% respectively.

As regards disease severity, a large Swedish study found that two doses of vaccine provided 54% protection against the need for hospitalisation following BA.1 or BA.2 infection, with that increasing to 80% following the third vaccine dose.

The obvious message here is to get that third or fourth booster shot as soon as possible.

I’ll summarise this briefly here, as we will want to come back to it, but these protection data fit very well with what we know from the analysis of serum neutralising antibody titres for the Omicron variants (#21, #93). The third and fourth shots with the current vaccine are bringing up cross reactive antibodies to Omicron BA.1 and BA.2 that are not detected after two-dose priming. What we also know is that these serum antibody levels fall off at a predictable rate after the booster shot, though it is likely that memory B cell populations with the capacity to differentiate into antibody secreting plasma cells will have increased in numbers and be primed for rapid recall (#93) after a further vaccination dose, or natural infection with the SARS-CoV-2 virus.

What that suggests is that protection against infection following these vaccine boosts, which likely depends on the immediate availability of antibodies, will fall off as serum antibody levels drop with time. The capacity to limit severe disease (#96), which could well be a function of antibody production from the restimulated memory B cell compartment, will, though, still be there to protect us from the worst (at least in the acute phase) of this infection. Another factor is that preventing severe disease may also involve the engagement of primed and restimulated CD8+ T cells (#34). But, as things stand, we don’t have much data showing that. Again, we’ll come back to this discussion later.

Also, what we have not addressed here is the historical data on vaccine protection against LC in vaccinated or unvaccinated people infected with other SARS-CoV-2 variants. Then there’s the question whether, even if vaccination does not fully protect against the development of LC, does it limit the duration and severity of symptoms? Again, we have to look back to what the much more extensive studies that were done pre-Omicron.

To be continued.