Low responses to mRNA COVID-19 vaccines in those older than 80 vs <60 years and in recipients of solid organ transplants
On 27 April 2021, a paper, published in the journal CID, reported important differences in immune responses by age to the Pfizer mRNA COVID-19 vaccine. Similar concerns were raised just over a week later in a letter to JAMA about recipients of solid organ transplants.
The CID study compared outcomes in 176 participants (roughly two-thirds were women) who were either older than 80 or younger than 60. 
However, the mean age in each group was 88 years (range 80 to 100) vs 42 years (range: 19 to 59), respectively and the paper didn’t comment on whether the age effect was continuous.
Although the majority of participants in both groups produced specific IgG antibody titres against SARS-CoV-2 spike, these were significantly lower by 2.8 fold in the older cohort. Although responses to the second vaccine dose did increase in both groups, the mean titre still remained significantly lower in the >80 year old group. These levels directly correlate with protection from infection.
The percentage of participants with undetectable titre levels two weeks after the second vaccine dose was 31% vs 2% in the oldest vs younger group respectively.
Also of note, in this study, symptoms post-vaccination were not related to later immune response.
The study recommends suggest close monitoring of this population that might require an increased vaccine dose to ensure stronger and long lasting protection.
However, as this issue of HTB was being sent out a letter to JAMA reported significantly poorer responses to mRNA responses in 658 solid organ transplant recipients. 
Only 15% participants (95% CI, 12% to18%) had a measurable antibody response after the first dose. This was after a median of 21 days (IQR: 18-25). After a median of 29 days after the second dose (IQR: 28 to 31) after dose 2, antibody was detectable in 54% participants (95% CI: 50% to 58%).
Overall, of the 658 participants, 98 (15%) had measurable antibody responses after both dose; 301 (46%) had no antibody response after either dose; and 259 (39%) only developed a response after dose 2. Poor humoral response was persistently associated with use of antimetabolite immunosuppression.
Although the CID study was only using one vaccine and did not report clinical outcomes the results suggest that people at highest risk because of their age, might need a different vaccination schedule. This might be just as important for other groups with reduced immune function, including transplant recipients and some people living with HIV.
It shows the importance of vaccines studies including a wider age range and higher proportion of older participants. Many studies, for example, only aim for 25% enrolment of people older than 65.
This highlights the importance of similar data for other vaccines and for other vulnerable groups, including people living with HIV who have very low CD4 counts (less than 50, but maybe <200 cells/mm3). Until available, caution might be important before assuming vaccine protection as lock down recommendations are eased.
The results from the recipients of solid organ transplant add to these concerns.
This also shows an important role for alternative approaches to vaccines, for example, ongoing research using broadly neutralising monoclonal antibodies.
Postscript: French guidelines now routinely recommend a third vaccine dose in people who have significantly reduced immune function. 
- Müller L et al. Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination. Clinical Infectious Diseases, ciab381, doi:10.1093/cid/ciab381. (27 April 2021).
- Boyarsky BJ et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. doi:10.1001/jama.2021.7489. (5 May 2021).
Collins S. France routinely recommends third dose of COVID-19 vaccine for some people with reduced immune function. HTB (11 May 2021).
Note: this article was amended on 5 May to include the JAMA report on 5 May 2021 and on 11 May to add the postscript on French guidelines.