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. 2022 Aug;28(8):1126-1133.
doi: 10.1016/j.cmi.2022.03.003. Epub 2022 Mar 11.

Characteristics associated with serological COVID-19 vaccine response and durability in an older population with significant comorbidity: the Danish Nationwide ENFORCE Study

Ole Schmeltz Søgaard  1 , Joanne Reekie  2 , Isik Somuncu Johansen  3 , Henrik Nielsen  4 , Thomas Benfield  5 , Lothar Wiese  6 , Nina Breinholt Stærke  7 , Kasper Iversen  8 , Kamille Fogh  6 , Jacob Bodilsen  4 , Mette Iversen  6 , Lene Surland Knudsen  6 , Vibeke Klastrup  9 , Fredrikke Dam Larsen  7 , Sidsel Dahl Andersen  9 , Astrid Korning Hvidt  9 , Signe Rode Andreasen  9 , Lone Wulff Madsen  3 , Susan Olaf Lindvig  3 , Anne Øvrehus  10 , Sisse Rye Ostrowski  11 , Christiane Abildgaard  3 , Charlotte Matthews  2 , Tomas O Jensen  2 , Dorthe Raben  2 , Christian Erikstrup  12 , Thea K Fischer  13 , Martin Tolstrup  7 , Lars Østergaard  7 , Jens Lundgren  14 ; ENFORCE Writing Group
Affiliations

Characteristics associated with serological COVID-19 vaccine response and durability in an older population with significant comorbidity: the Danish Nationwide ENFORCE Study

Ole Schmeltz Søgaard et al. Clin Microbiol Infect. 2022 Aug.

Abstract

Objectives: To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies.

Methods: Adults without history of SARS-CoV-2 infection from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase 4 study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90, and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 after first vaccination. Nondurable vaccine response was defined as day-90 responders who no longer had significant responses by day 180.

Results: Of 6544 participants completing two vaccine doses (median age 64 years; interquartile range: 54-75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by an mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hyporesponsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG and 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type, and number of comorbidities were associated with all four outcomes. Additionally, age ≥75 years was associated with hyporesponsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds ratio: 1.59; 95% confidence interval: 1.25-2.01) but not for Spike IgG.

Discussion: Comorbidity, male sex, and vaccine type were risk factors for hyporesponsiveness and nondurable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-second-vaccination levels for most individuals after 6 months.

Keywords: Antibody; COVID-19; Immunity; SARS-CoV-2; Vaccination.

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Figures

Fig. 1
Fig. 1
Plasma levels of SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibody levels at each study visit. (A) Plasma levels of SARS-CoV-2 Spike IgG at each study visit by vaccine type. (B) Plasma levels of SARS-CoV-2 Spike IgG at each study visit by age group and level of comorbidity. (C) Plasma concentration of Spike-ACEII-receptor blocking antibodies according to vaccine type. (D) Plasma concentration of Spike-ACEII-receptor-blocking antibodies according to age group and level of comorbidity. CCI, Charlson Comorbidity Index.
Fig. 2
Fig. 2
Risk factors for COVID-19 vaccine hyporesponsiveness in a multivariate logistical regression model according to (A) Spike IgG and (B) Spike-ACE2-receptor-blocking antibody levels at day 90.
Fig. 3
Fig. 3
Risk factors for COVID-19 vaccine hyporesponsiveness in a multivariate logistical regression model according to (A) Spike IgG and (B) Spike-ACE2-receptor-blocking antibody levels at day 180.
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