BMI, Age, and Sex Affect COVID-19 Vaccine Antibody Response

Miriam E. Tucker

March 03, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published February 26 as a preprint.

The study involved 248 healthcare workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

"The findings imply that female, lean and young people have an increased capacity to mount humoral immune responses compared to male, overweight and older populations," say Raul Pellini, professor at the IRCCS Regina Elena National Cancer Institute, Rome, Italy, and colleagues.

"To our knowledge, this study is the first to analyse Covid-19 vaccine response in correlation to BMI," they note.

"Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people," they write.

If the data are confirmed by larger studies, "giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population."

Results Contrast With Pfizer Trials of Vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published December 31, 2020, in The New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Asked to comment, Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University School of Medicine, New Haven, Connecticut, noted that although the current Italian study showed somewhat lower levels of antibodies in people with obesity compared to people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

"These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection," Iwasaki told Medscape Medical News.

Indeed, Pellini and colleagues point out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity compared to lean individuals.

However, they say, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

"The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T-cells, which can directly kill infected cells," the authors note.

Findings Reported in British Newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as, Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study and Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says. In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or "is yet to be scrutinised by fellow scientists."

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

"We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset," Danny Altmann, a professor of immunology at Imperial College London, told The Guardian newspaper.

"It confirms that having a vaccinated population isn't synonymous with having an immune population, especially in a country with high obesity, and emphasises the vital need for long-term immune monitoring programmes," he added.

Antibody Responses Differ by BMI, Age, and Sex

In the Italian study, the participants ― 158 women and 90 men ― were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2 binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) in comparison with those aged 47 to 56 years (239.8 AU/mL; P = .005), those aged 37 years and younger vs those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37 to 47 years vs those older than 56 years (330.9 vs 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5 to 24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL) compared with persons with preobesity, defined as BMI of 25 to 29.9 kg/m2 (222.4 AU/mL), and those with obesity (BMI ≥30 kg/m2; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

"Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems," the researchers note.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

"We strongly believe that our results are extremely encouraging and useful for the scientific community," Pellini and colleagues conclude.

The authors have disclosed no relevant financial relationships. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

medRxiv. Published February 26, 2021. Full text

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