Do Antibody Levels Predict Protection Against COVID?

Higher SARS-CoV-2 antibody levels in fully vaccinated individuals translated to lower rates of infection for nursing home residents and staff during the Delta wave, though not when Omicron hit, a cross-sectional study showed.

In a study group of over 2,000 fully vaccinated residents and staff at West Virginia nursing homes, median SARS-CoV-2 antibody levels were twice as high among those who avoided breakthrough infections during Delta compared with those who later contracted COVID (P=0.002), reported Sally Hodder, MD, of West Virginia University School of Medicine in Morgantown, and co-authors.

But when Omicron hit, antibody levels for those who later became infected and those who never did were no different (P=0.70).

"Data presented in this study are not conclusive in providing a serologic correlate of protection against SARS-CoV-2 infection," the group wrote in JAMA Network Open.

Anti-receptor binding domain (RBD) IgG antibody levels decreased over time after either vaccination or infection, and were significantly lower among fully vaccinated participants without a history of COVID-19 compared with boosted individuals (with or without a prior infection) and non-boosted participants with a past breakthrough infection.

"Fully vaccinated, non-boosted individuals who had previously experienced vaccine breakthrough infections had significantly higher antibody levels compared with boosted participants with or without a history of infection," Hodder's group noted.

"This observation demonstrates that booster doses may not restore antibody levels equivalently to breakthrough infections," they continued. "However, given that vaccination reportedly reduced the need for mechanical ventilation and death by 94%, keeping at-risk individuals vaccinated could prove beneficial to them and help reduce resource demands associated with the management of severe SARS-CoV-2 infection."

The researchers included 2,139 residents (n=1,086) and staff (n=1,053) from 41 nursing homes, who from September to November 2021 had a serum specimen collected. All were fully vaccinated with either Pfizer, Moderna, or Johnson & Johnson's vaccine, and one-fourth also received a booster dose. Prior infection was reported by 28%.

Median age of participants was 67 years old, more than three-fourths were women, and the vast majority were white (96%). Overall, 219 breakthrough infections occurred from January 2021 to January 2022, among a similar proportion of residents (11%) and staff (9%), with the vast majority occurring during the Delta and Omicron surges.

Researchers highlighted that a significantly higher percentage of residents had negative test results for anti-RBD IgG antibodies compared with staff (9% vs 4%, P<0.001).

Measurement of neutralizing antibody levels as correlates of protection was conducted in a subset of 95 patients with a SARS-CoV-2 infection following specimen collection. Of those, 78 had not received a booster, with 18 of these infections occurring during the Delta wave and 60 during Omicron.

During Delta, antibody index levels -- which were "calculated by dividing the sample signal by the mean calibrator signal," Hodder's group explained -- were a median 2.3 (95% CI 1.8-2.9) among participants who later experienced breakthrough infections and 5.8 (95% CI 5.5-6.1) for those who never went on to have a subsequent infection.

But during the Omicron wave, no differences were recorded between the infection (median 5.9, 95% CI 3.7-11.1) and non-infection groups (median 5.8, 95% CI 5.6-6.2).

Lower antibody levels among individuals infected during Delta may "have resulted as a time-artifact because booster dose recommendations were initiated after onset of the Delta surge," Hodder and colleagues pointed out.

Anti-RBD IgG levels were higher among the nursing home residents and staff with a recent exposure (infection or vaccination). When examining groups with exposures 14 to 77 days prior to specimen collection, median antibody index levels were as follows:

• Fully vaccinated participants, no history of infection: 8.0 (95% CI 2.5-11.3)
• Boosted individuals, no infection: 14.0 (95% CI 13.1-14.7)
• Boosted individuals with previous infection: 16.6 (95% CI 15.9-17.3)
• Non-boosted with breakthrough infection: 17.7 (95% CI 17.0-18.1)

The study was limited by the fact that most infections were documented 2 to 3 months after antibody levels were checked, the authors acknowledged, so they do not precisely reflect levels at the time of infection. Researchers pointed out, however, that antibody levels would not have been higher in these participants unless they got a booster after the blood test. In addition, the majority of participants were white women, so the results may not be generalizable to other groups.

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