How long is too long between vaccine doses? Spanish scientists explain

CONCERNS among members of the public in Madrid about their second vaccine being overdue have been assuaged by medical experts, who stress the level of protection will not best compromised.

Extra doses are being delivered to Spain's coastal regions so that residents in inland areas and big cities spending their summer elsewhere can still have both jabs, which the Greater Madrid region claims has led to a shortage in its own stock – something the government denies, saying enough phials to cover all those now due have been sent on.

And the appointment system in the capital region facing backlog may not be a problem either, professionals in the sector say.

Many Madrid residents say they have not received a text message summoning them for their second jab, although in other regions, SMS communications give dates and times for both appointments from the start.

The vaccine hotline for the capital, the freephone 900 102 112 number, stresses there is no need to have received a text message, or have a QR code in accordance with the region's system – all they require is to book their date and turn up with their identity document.

Spain's health ministry, in accordance with the European Medicines Agency (EMA), originally stated that the second Pfizer and Moderna injections should be given 21 days apart – unlike the AstraZeneca, which has been found to be more effective when given 12 weeks apart, and the Janssen, which only requires one dose.

Is 28 days too long?

Panic is becoming widespread in regions where appointments for second jabs are coming at 25 or 28 days after the first – in most cases, for Pfizer or Moderna inoculations, since Spain ended up reserving the AstraZeneca for the over-60s only, has not ordered any more doses in, and plans to donate the surplus supply to poorer countries.

Madrid's regional health minister Enrique Ruiz Escudero says: “The second dose can be up to 42 days after the first.

“The EMA says it can stretch out to 42 days if needed, but our aim is to get it as close as possible to day 21,” he says.

Secretary of State for health, Silvia Calzón, adds: “These days, no regional government should have any problems with a gap in stock supply for administering the second dose on time and in accordance with the prospectus.”

This prospectus, both the one issued by the EMA and the version produced by the Spanish Agency for Medicines and Healthcare Products (AEMPS), state that the Pfizer-BioNTech vaccine retailed under the brand name of Comirnaty, an RNA-messenger (RNAm) formula, showed an effectiveness level of 95% in a clinical trial of 44,000 participants who received either two doses or a placebo 'separated by 21 days'.

But it adds: “The analysis of effectiveness levels (in persons aged over 16 years) included participants who received their second dose at between 19 and 42 days from the first dose.”

An endorsement added in January states: “The majority (93.1%) of those who received the vaccine were given a second dose between 19 and 23 days after the first dose.”

As to whether this means there is no evidence the vaccine is effective if the second dose is more than 23 days from the first, chairman of the Spanish Immunology Society and head of Immunology at Santander's Marqués de Valdecilla Hospital, Dr Marcos López Hoyos, says: “No. The EMA, the technical organisation which has studied the data the most and the best, says that up to 42 days, the level of effectiveness is the same.”

He highlighted 'prior experiences' when the vaccine campaign started at the very beginning of this year, when second doses of the Pfizer were delayed due to a shortage of the formula.

Jabs at 40 days early in the year 'have proven effective'

“There was the same controversy, because people were waiting anything from 28 to 40 days for their second jab, but it has still proven effective; from the point of view of immunological response and the introduction of antibodies into the system, there's basically no problem.

“The ideal scenario is to get as close as possible to the 21 days, but the vaccine does not lose effectiveness.

“It's important to administer the second dose as soon as possible, because having had both means you're protected much more against new strains of the virus, especially the Delta, as we've seen from medical data.”

Research in the USA found that after the first dose of any of the double-jab vaccines, protection against the original variant of the SARS-CoV-2 was barely 30%, and against the more recent mutations of the virus, less than 13% - but after the follow-up shot, protection levels in all cases and against all known strains were at least 95%.

Dr Fernando Moraga-Llop of the Spanish Vaccination Association says there is 'no problem' if 'for example, due to causes outside our control', the second dose 'has to be delayed by a few weeks'.

“The prospectus considers various intervals – just that those outside the 19-23 days had fewer participants during clinical trials,” he explains.

“Our biggest body of evidence comes from those given shots between 19 and 23 days apart, but that doesn't mean other intervals during the trials have no evidence or insufficient evidence; they do have it, but just not as much.”

He concurs with Dr López Hoyos about second doses being given as soon as possible, however, to guarantee maximum protection against the newer, more aggressive or more contagious strains of the virus.

The EMA initially recommended a gap of 'at least 21 days', but the World Health Organisation (WHO) updated this advice on June 25 to read 'at least 21 to 28 days'.

And the WHO is even contemplating the possibility that the time between shots could stretch out to up to 12 weeks, where a country or region is experiencing supply problems or is going through a period of exceptionally-high contagion rates – here, spacing out doses more would mean 'far greater vaccine cover for high-priority communities', such as the elderly or immune-compromised.

How many are now fully immunised in Spain?

In Spain, just over half the country is now fully immunised, with either the Janssen single-jab formula or with both doses – in fact, the vast majority will have been given the Pfizer.

Just over 24 million people out of a population of 47.1 million have now completed their vaccines, although many more have had at least their first dose, and depending upon region and area health department, those now receiving their first are aged anything from their 40s to their early 20s.

For the over-80s, 100% of the population is now fully immunised, whilst 97% of the 70-79 age group are, 81% of those aged 60 to 69, rising to 85% of those aged 50 to 59 – largely because the 60-69 community have tended to be given AstraZeneca jabs, where the second dose is given after a longer interval – and 62% of those aged 40 to 49.

The figures for those not yet inoculated – 3% of those aged 70 to 79, 19% of the 60-69 group or 15% of those in their 50s – are partly due to longer stretches between AstraZeneca shots, partly due to having to rearrange appointments where attendance has not been possible, and partly due to a certain, albeit very small, percentage who have declined to be vaccinated.

In Spain as a whole, the vaccine take-up rate has been among the highest in Europe, particularly with the Pfizer and Moderna formulae.

One other factor that has come out of the worries about overdue second jabs is a warning that these should never be given less than 19 days after the first.

Dr Moraga-Llop says: “A second dose less than the minimum of 19 days would not be valid, and you'd have to repeat it 21 days later – a third dose, because the second would not provide any additional protection on top of the first.”