COVID-19: Every third infected but unvaccinated person has no detectable antibodies one year after infection

Both infection and vaccination against SARS-CoV-2 help build a population’s immunity to the virus – an important factor in deciding when and to whom booster shots should be offered. Although immunity to a pathogen is more than just antibodies, the simplest strategy for assessing population immunity is to conduct seroepidemiological studies (i.e., quantifying virus-specific antibodies in a given population).

“Most serological studies conducted after COVID-19 vaccination focused on specific groups such as medical workers, did not distinguish between people with or without previous infection, or had no clinical and immunological data of the infection,” explains Manolis Kogevinas, ISGlobal researcher and senior co-author of the study along with Carlota Dobaño, also a researcher at ISGlobal.

In this study, the research team carried out a second measurement in a population-based cohort from Catalonia (COVICAT study – GCAT cohort) six months after the start of the vaccination campaign (the first was shortly after the first delivery) to monitor the amount and type of antibodies against five viral antigens (the whole spike (S) protein, the RBD receptor binding domain, the S2 fragment, the whole nucleocaspid (N) protein or the N-terminal fragment). They also used information from a questionnaire and health records to identify potential factors that determine the magnitude and duration of the antibody response in unvaccinated, vaccinated, or vaccinated and infected individuals. A total of 1,076 people between the ages of 43 and 72 were included in the analysis.

The results produced three main conclusions: first, that antibodies were undetectable in 36% of infected but unvaccinated individuals almost a year after infection, particularly among those over 60 years of age and smokers.

Second, this vaccination induced significantly higher antibody levels in people with a previous infection than in people without a previous infection; and that these values ​​were strongly associated with the magnitude of the response during infection. “Our data underscores the importance of vaccinating people, even if they have previously been infected, and confirms that hybrid immunity is superior and more durable. This means that people who have been vaccinated but have not become infected need a booster earlier than those who did,” stresses Marianna Karachaliou, first author of the study together with Gemma Moncunill.

Third, the factor most strongly associated with antibody levels is the type of vaccine – Moderna’s Spikevax produced the highest levels of antibodies. Other factors also seem to play a role: people over 60 or with mental illnesses had lower antibody levels after vaccination. “The link between mental health and antibody responses needs further study, but it is known that people with conditions such as depression, chronic stress or schizophrenia are generally less responsive to vaccination,” explains Dobaño.

Among those vaccinated, only 2.1% had no antibodies at the time of the test and about 1% had a breakthrough infection. “However, it should be noted that this study was conducted before the omicron variant became dominant,” warns Kogevinas.