Charité study proves delayed vaccination response in the elderly
Throughout Germany, there are reports of SARS-CoV-2 outbreaks in nursing homes despite full vaccination of the residents. To better understand this phenomenon, a research team from Charité – Universitätsmedizin Berlin has virologically analysed such an outbreak in a Berlin facility and studied the immune response of elderly people to vaccination. The results, published in the journal Emerging Infectious Diseases*, demonstrate the effectiveness of the vaccination, but also indicate a delayed and slightly reduced immune response in the elderly. Based on these data, the researchers emphasise the importance of vaccinating contact persons to better protect this particularly vulnerable risk group.
The effectiveness of the COVID-19 vaccination with the vaccine from BioNTech/Pfizer is considered to be very high: one week after the second dose, it prevented more than 90 per cent of symptomatic infections with SARS-CoV-2 in the registration studies. The high effectiveness of the vaccination has also been confirmed in large observational studies in the population. Nevertheless, infections can still occur in individual cases after vaccination. But what explains why there are still major outbreaks in nursing homes despite complete vaccination of residents? In two related papers, an interdisciplinary research team at Charité now confirms what medical professionals had suspected based on their experience with other vaccines: The immune system of the elderly does not react quite as efficiently to vaccination as that of younger people.
For the study, the researchers first worked through an outbreak in a Berlin care facility that had been noticed in February. In addition to 11 nursing staff without complete vaccination protection, 20 residents had also been infected with SARS-CoV-2. All but four of them had been fully vaccinated with the BioNTech/Pfizer vaccine. While the four unvaccinated residents became so severely ill that they had to be treated in hospital, only about one third of the vaccinated residents showed signs of illness such as coughing or shortness of breath. By determining the amount of virus in the swab samples, the team found that vaccinated people tended to have less virus in their throat than unvaccinated people. In addition, the virus was detected in them over a significantly shorter period of time, on average over just under 8 days instead of 31 days. Four other vaccinated residents did not contract SARS-CoV-2 despite exposure during the outbreak. Further transmission to other areas of the facility was prevented by hygiene measures.
Nevertheless, two of the 16 vaccinated COVID-19 patients had to be admitted to hospital. There, one patient died of a cerebral haemorrhage after a sharp rise in blood pressure. A second patient died in the home after she had not excreted any virus for more than two weeks. Neither of the deceased had developed respiratory symptoms. The researchers therefore do not assume a causal connection with the SARS-CoV-2 infection.
„On the one hand, we see from this outbreak that the vaccination protected the nursing home residents overall, because their courses of illness were significantly milder,“ says Dr. Victor Corman, Deputy Head of the Coronavirus Consiliary Laboratory at the Institute of Virology at Charité and one of the three lead authors of the study. The scientist from the German Center for Infection Research (DZIF) adds: „The shorter viral shedding also probably prevented further transmissions. At the same time, the accumulation of infections makes it clear that the high efficacy of the vaccination sometimes does not take full effect in the elderly.“
The scientists see one of the possible reasons for this in the fact that the outbreak was triggered by the virus variant B.1.1.7, now called alpha, which is associated with a higher amount of virus in the throat and greater transmissibility. They found a second reason in the immune response of those affected to the vaccination itself. For this purpose, the research team compared the immune response to the BioNTech/Pfizer vaccine in patients over 70 years of age in a GP practice with that of Charité employees, who were on average 34 years old. Blood analyses showed that already three weeks after the first dose, about 87 percent of the younger patients had formed antibodies against SARS-CoV-2; among the older patients, it was only about 31 percent. One month after the second dose, almost all young vaccinees (99 per cent) had SARS-CoV-2-specific antibodies in their blood; among the older ones, it was about 91 per cent. In addition, the antibodies matured more slowly in the older ones, so they were less able to bind the virus. And the second important arm of the immune response, the T-cell response, was also weaker.
„Our study thus shows that in older people the immune response after vaccination is significantly delayed and does not reach the level of young vaccinees,“ summarises Prof. Dr. Leif Erik Sander, vaccine researcher from the Medical Clinic with a focus on infectiology and pneumology at the Charité and also lead author of the study. „You cannot calculate the effectiveness of the vaccination based on a single outbreak. Overall, the infection figures in nursing homes have fallen dramatically since the vaccination campaign began. But there are individual outbreaks and then older people seem to be more susceptible than younger people, because in some the immune response is somewhat weaker.“
Private lecturer Dr Florian Kurth, the third lead author of the study from the Medical Clinic with a focus on infectiology and pneumology at the Charité, emphasises: „It is true that only just under one in ten of those over 70 years of age have no antibodies in their blood after complete vaccination. But since we currently have no way of identifying those with low vaccination protection on the basis of individual readings, we cannot rely on vaccination alone to protect this particularly vulnerable risk group. Instead, at this point in time, when large parts of the population are not yet immune, hygiene measures and testing still play an important role. In particular, vaccination of nursing staff and visitors is immensely important to prevent outbreaks in nursing homes. In the medium term, further booster vaccination for older people is certainly also an option to improve their vaccination protection.“
*Tober-Lau P et al. Outbreak of SARS-CoV-2 B.1.1.7 Lineage after Vaccination in Long-Term Care Facility, Germany, February-March 2021. Emerg Infect Dis (2021). doi: 10.3201/eid2708.210887
Schwarz T et al. Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly, Germany. Emerg Infect Dis (2021). doi: 10.3201/eid2708.211145
COVIM project of the University Medicine Network
Parts of this work were done within the framework of the collaborative project „COVIM – Determination and Utilisation of SARS-CoV-2 Immunity“. The COVIM consortium is investigating who is immunologically protected from SARS-CoV-2 infection, by what means and for how long, and how immunological protection can be transferred from a few immune individuals to many non-immune individuals. The project is coordinated by the Charité and the University Hospital Cologne. COVIM is one of 13 collaborative projects within the Network University Medicine (NUM), which was initiated and coordinated by Charité and is funded by the Federal Ministry of Education and Research. The NUM unites the strengths of the 36 university hospitals in Germany.
Study platform for research into COVID-19 at Charité
The basis for generating the data now published was the Pa-COVID-19 study platform, the central longitudinal registry study for COVID-19 patients at the Charité. It aims to investigate COVID-19 patients clinically and molecularly quickly and comprehensively in order to identify individual risk factors for severe forms of progression as well as prognostic biomarkers and therapeutic approaches. The protocol for the study is published at https://link.springer.com/epdf/10.1007/s15010-020-01464-x?sharing_token=ciyCI6nQBUOUgDXydZOpWfe4RwlQNchNByi7wbcMAY7AEmHJ4Pa6r2rpBujdn0yew9hlBtgcIP5cHvmMwc1MWUToEIt4WUmt-7fjN4D3K6V1PRm9s_7-7JIL86_beVOPpoF7Qd0KgM5xmttzdwhvhqvATBk4F8B3Vwb9HWz1vUs=