A startling new study by researchers at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy, indicates that obesity may reduce the immune response to the current coronavirus disease 2019 (COVID-19) vaccines, along with other factors like age and sex. This could have significant implications for vaccination strategies in obese people. The team has released their findings on the medRxiv* preprint server.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, has seriously affected human health, social interactions and economic activity throughout the world. Initially, non-pharmaceutical interventions (NPIs) were put in place all over the globe, from lockdowns at the most severe level, to region-specific or zone-specific isolation measures, along with hand and face hygiene.

However, the severe disruption that such measures present to normal economic and social life make many of these measures untenable in the long-term. While targeted and effective antiviral drugs are yet to be identified to treat the disease in those infected with SARS-CoV-2, vaccine development may be the only way out.

Vaccines provide a ray of hope

At present, there are almost 240 vaccine candidates, with several already having received emergency use authorization in the US, the UK, Europe, and other continents.

The first to be approved was the messenger ribonucleic acid (mRNA) BNT162b2 vaccine (Pfizer/BioNTech), which showed 95% efficacy in preventing symptomatic disease after two doses, and safety comparable to that of other vaccines over the short term.

However, no definitive data is available on how far this vaccine prevents infection. Many researchers use antibody titers, particularly neutralizing antibody titers, as a proxy for this outcome.

This is based on the known relationship between neutralizing activity in serum and protection against respiratory viruses such as influenza or respiratory syncytial virus, showing this to be a functional biomarker of protection against infection with the agent in vivo.

Earlier, it has been shown that a single dose of this vaccine, as well as the Moderna vaccine, when given to seropositive (previously infected) individuals, leads to high neutralizing antibody titers compared to those achieved with two vaccine doses in SARS-Cov-2-naïve individuals. Further studies are required to validate these findings.

Study details

The current preprint describes the efficacy of the BNT162b2 vaccine in a population of healthcare workers. The antibody titer was measured at seven days from the second dose, in 248 healthcare workers (HCWs), and compared with age, sex and body mass index (BMI).

Of this group, 158 were women, and the median age was 47 years. All participants tested negative for infection by a nasopharyngeal swab test at baseline, which was repeated at seven days from the second dose.

A neutralizing antibody response developed to SARS-CoV-2 in almost 100% of the participants after two doses of the vaccine, with a single non-responder. Antibodies binding the S1/S2 subunits were found in the range of 3.8-2460 AU/mL, with a higher antibody geometric mean concentration (AbGMC) compared to that of convalescent sera from human subjects ~286 AU/mL vs 39 AU/mL, respectively.

The test used here was not designed to assay neutralizing activity. Still, a titer of 80 AU/mL is absolutely correlated with a 1:160 titer of the accepted neutralization assay, the plaque reduction neutralization test (PRNT90). In this context, therefore, neutralizing antibodies may be assumed to be present in 93% of participants, at least, who had titers of 80AU/mL or more.

Younger subjects had a higher antibody titer. This was also the case with women, at 339 AU/mL vs 212 AU/mL in men.

However, the BMI also showed a strong relationship with the vaccine's ability to induce an efficient humoral response. Lean and normal-weight subjects (BMI <25) showed higher antibody titers compared to overweight or obese subjects. This association persisted even when adjusted for age.

What are the implications?

Obesity is well-known to be a risk factor for progressive disease and mortality in COVID-19. Not only is infection more severe, but its duration is prolonged by about five days in people with a higher-than-normal BMI.

The negative effect on immunity elicited by current vaccines is perhaps due to the presence of low-grade inflammation in obese individuals. Obesity is also associated with lower gut microbial diversity, as well as in the nose and lungs, and with altered metabolism.

Earlier, gut microbial disturbances, as following antibiotic use, have been shown to be linked to lower efficacy of flu vaccines.

Obesity has been shown to reduce immune responses to other vaccines, including influenza, hepatitis B, and rabies. The current study establishes this relationship in the case of COVID-19 vaccines for the first time.

With a large, if not major, proportion of people in the developed world, especially in the USA, being clinically obese or overweight, the reduction in immunogenicity of the current vaccines in this group is a point of great concern.

In fact, "According to the latest data from the World Health Organization, 39% of adults aged 18 years and over were overweight, and 13% were obese."

This may underscore the need for the development of more efficient vaccination strategies for this group of people. For instance, they may need higher doses, or an additional dose of vaccine, for complete protection.

The sex-dependent difference in COVID-19 morbidity and mortality was also confirmed in this study of vaccine response, with women showing higher antibody responses. This has been seen earlier, with the trivalent inactivated seasonal influenza vaccination (TIV) and most other vaccines.

In fact, with TIV, only half the dosage given to males evokes a similar protective antibody response. The higher the serum testosterone levels, the lower the antibody levels following TIV vaccination.

Females, along with leaner and younger subjects, are therefore better at producing an antibody response to a pathogen. By showing this trend with respect to the current virus, the study contributes an important piece of information to the sum of COVID-19 knowledge.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.