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. 2022 Jul;292(1):127-135.
doi: 10.1111/joim.13471. Epub 2022 Mar 24.

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations

Devang K Sanghavi  1 , Shivang Bhakta  1 , Hani M Wadei  2 , Wendelyn Bosch  3 , Jennifer B Cowart  4 , Rickey E Carter  5 , Sadia Z Shah  2 , Benjamin D Pollock  6 , Matthew R Neville  6 , Sven P Oman  4 , Leigh Speicher  7 , Jason Siegel  1   8 , Ameya D Scindia  1 , Claudia R Libertin  3 , Katie L Kunze  9 , Patrick W Johnson  5 , Mark W Matson  10 , Pablo Moreno Franco  1   2   6
Affiliations

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations

Devang K Sanghavi et al. J Intern Med. 2022 Jul.

Abstract

Background: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge.

Methods: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders.

Results: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients.

Conclusions: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.

Keywords: COVID-19; SARS-CoV-2; antispike antibodies; delta; vaccine breakthrough.

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Conflict of interest statement

R. E. C. serves as an advisory board member for Anumana, Inc. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Consort diagram showing patient population selection.
Fig. 2
Fig. 2
Box plot presentation for antispike antibody titers (U/ml) by vaccination status. Boxes and horizontal bars denote interquartile range (IQR) and median of antispike antibody titer, respectively. The cut‐off value for a positive Elecsys ® Anti‐SARS‐CoV‐2 S assay is ≥0.80 U/ml, and in our study, the value ≥132 U/ml defined the high‐titer group. Whisker endpoints are equal to the maximum and minimum values below or above the median +/− 1.5 × IQR. The individual points are the observed titer levels by case after "jittering" to avoid overlapping points on the figure. The black points are the patients who did not expire whereas the gold points are those who died.
Fig. 3
Fig. 3
Sankey diagram of patient outcomes with high and low antispike antibody titers in the breakthrough and unvaccinated cohorts.
See this image and copyright information in PMC

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Supplementary concepts