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A study conducted at Sheba Tel Hashomer Hospital and published Thursday shows a consistent decline in the neutralizing antibodies six months after receiving the second dose of Corona vaccine, in all but one group: overweight people.

The study that was published in the New England Journal of Medicine (Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months) included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. However, obese participants (those with a BMI of ≥30) had a 31% increase in neutralizing antibody concentrations as compared with nonobese participants.


The study concluded that six months after receipt of the second dose of the BNT162b2 vaccine, the humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Humoral immunity, a.k.a. antibody-mediated immunity, is the immunity extended to the body through extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is named so because it involves substances found in the humors (body fluids), as opposed to cell-mediated immunity.

This prospective longitudinal cohort study involved healthcare workers at Sheba Medical Center, which includes 1600 beds and 14,739 healthcare workers, including employees, students, volunteers, and retired personnel. The distribution of the healthcare workers at Sheba Medical Center is as follows: 18% are physicians, 27% are nurses or nurse aides, 21% are paramedical personnel, and 34% are administrative or logistic employees. The study protocol was approved by the institutional review board at Sheba Medical Center.

All the participants in the study were healthcare workers who had been invited to participate in the study and provide peripheral-blood samples for serologic assays before receipt of the first vaccine dose and then monthly (every 28 days, within a window of ±14 days) for 6 months after receipt of the second vaccine dose. Written informed consent was obtained from all study participants.

Eligibility criteria included being age 18 or older, no SARS-CoV-2 infection before receipt of the first vaccine dose, and at least one serologic assay result after receipt of the second dose of vaccine. All the healthcare workers at Sheba Medical Center were required to report a daily health status on arrival at the hospital. If any Covid-19–associated symptom or exposure to a SARS-CoV-2–infected person at work, at home, or in the community was reported, a PCR test for SARS-CoV-2 was required.

In addition, monthly serologic follow-up was conducted during the study period. Participants with a substantial increase in IgG antibody levels or neutralizing antibody titers (≥4 times) between consecutive tests were tested for anti-N antibody to rule out a Covid-19 breakthrough infection and, if positive, were withdrawn from the study.

Participants were notified of their personal test results. Participants whose IgG and neutralizing antibody titers decreased to below the test cutoff level tended not to return for follow-up visits. These and other missing outcomes were accommodated through the linear mixed model that was used in the analysis.

The study was conducted from December 19, 2020, to July 9, 2021. Of the 12,603 vaccinated healthcare workers who were eligible for the study, 4868 were recruited for study participation. During the study period, 20 participants had a breakthrough SARS-CoV-2 infection, and 5 had a positive anti-N result. A total of 14,736 IgG assays and 4521 neutralizing antibody assays were performed.

IgG levels were evaluated at least once for all study participants during the 6 months of follow-up and at least twice for 2631 participants (54.0%). The neutralizing antibody subgroup included 1269 participants (26.1%) who underwent at least one neutralizing antibody test; 955 of these participants (75.3%) were tested at least twice. Data on age and sex were available for all study participants. Overall, 3808 participants (78.2%) responded to the computer-based questionnaire and were included in the mixed-model analysis.

Overall (regardless of sex and age group), obese participants were at lower risk for having lower neutralizing antibody titers than nonobese participants. Participants with immunosuppression were more likely than healthy participants to have a below-average neutralizing antibody titer.

Obese persons had a significantly higher neutralizing antibody titer during long-term follow-up than nonobese participants. The study authors noted that obesity is associated with severe Covid-19, and disease severity is associated with a higher Covid-19 humoral immune response. A recent study showed that SARS-CoV-2 neutralizing antibodies are positively associated with BMI. Yet, it is still unclear whether vaccinated obese persons are at higher or lower risk for breakthrough infection and whether the relatively high humoral response to the vaccine is protective.


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