Antibody levels versus vaccination status in the outcome of older adults with COVID-19

Abstract

BACKGROUNDDespite the currently prevailing, milder Omicron variant of COVID-19, older adults remain at elevated risk of hospital admission, critical illness, and death. Loss of efficacy of the immune system, including reduced strength, quality, and durability of antibody responses, may render generalized recommendations on booster vaccinations inadequate. There is a lack of data on the efficacy of antibody levels in older adults and on the utility of vaccination status versus antibody levels as a correlate of protection. It is further unclear whether antibody levels may be used to guide the timing of booster vaccinations in older adults.METHODSWe conducted a prospective multicenter cohort study comprising hospitalized patients with COVID-19. Anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The primary endpoint was in-hospital mortality. Patients were stratified by age, antibody levels, and vaccination status. Multiple logistic regression and Cox regression analyses were conducted.RESULTSIn total, 785 older patients (≥60 years of age [a]) and 367 controls (<60a) were included. After adjusting for confounders, risk of mortality, ICU admission, endotracheal intubation, and oxygen administration was 4.9, 2.6, 6.5, and 2.3 times higher, respectively, if antibody levels were < 1,200 BAU/mL (aOR, 4.92 [95%CI, 2.59-9.34], P < 0.0001; aOR, 2.64 [95%CI, 1.52-4.62], P = 0.0006; aOR, 6.50 [95%CI, 1.48-28.47], P = 0.013; aOR, 2.34 [95%CI, 1.60-3.343], P < 0.0001). Older adults infected with the Omicron variant were approximately 6 times more likely to die if antibody levels were < 1,200 BAU/mL (aOR, 6.3 [95% CI, 2.43-16.40], P = 0.0002).CONCLUSIONAntibody levels were a stronger predictor of in-hospital mortality than vaccination status. Monitoring antibody levels may constitute a better and more direct approach for safeguarding older adults from adverse COVID-19 outcomes.

Keywords: Clinical practice; Infectious disease; Vaccines.

Figure 1. Patient flow diagram.

Figure 2. Patient outcomes for older (≥60 years) and younger adults (<60 years) in percentages regarding in-hospital mortality, intensive care treatment, endotracheal intubation, and oxygen administration by antibody level and vaccination status.

Bottom row: Outcome by antibody level in vaccinated older adults and older adults infected with the Omicron variant. BAU binding antibody units.

Figure 3. Cumulative survival over time in older adults.

(A–D) Kaplan-Meier curves with 95% CI, for cumulative survival over time in older adults (≥60 years) by high and low anti–SARS-CoV-2 spike antibody level (above and below 1,200 BAU/mL) (A), by vaccination status (B), by antibody level in vaccinated older adults (C), and by antibody level in older adults infected with the Omicron variant (D). Number censored: cumulative number of patients lost to follow-up. Statistical significance was determined by log rank (Mantel-Cox) test. BAU, binding antibody units; nonvacc., nonvaccinated patients.

Figure 4. Risk of outcome in older adults.

(A–D) Risk of outcome in older adults, aged 60 years or older, by antibody level above versus below 1,200 BAU/mL. (A) and vaccination status (B); risk of outcome by antibody level in vaccinated older adults (C) and in older adults infected with the Omicron variant (D). Unadjusted and adjusted odds ratios are shown for the outcomes oxygen administration, endotracheal intubation, intensive care admission, and in-hospital mortality. Unadjusted and adjusted hazard ratios are shown for in-hospital mortality. Adjusted odds and hazard ratios were calculated by multiple logistic and Cox regression analyses and adjusted for age, BMI, SARS-CoV-2 variant, type 2 diabetes, hypertension, CAD, heart failure, stroke/TIA/CVD, and renal disease.