Anti-spike antibody level is associated with the risk of clinical progression among subjects hospitalized with COVID-19 pneumonia: results from a retrospective cohort study

Abstract

Purpose: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear.

Methods: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status.

Results: The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p < 0.001). After 30 days, 134 patients experienced death or MV. Among vaccinated individuals, higher anti-S levels correlated significantly with lower death/MV risk (per log₂ increase, OR 0.88, 95%CI 0.81-0.97), irrespective of age and solid malignancies. Among unvaccinated, a marginally protective effect was observed (OR 0.86, 95%CI 0.73-1.01), independent of age, immunosuppressive therapy, and diabetes. Adjustment for monoclonal antibody treatment strengthened the association (OR 0.81, 95%CI 0.68-0.96).

Conclusion: This study suggests that levels of anti-S antibodies can predict critical or fatal outcomes in COVID-19 pneumonia patients, regardless of vaccination. Whether anti-S Ab could guide risk assessment and vaccination boosting merits further evaluation.

Keywords: Anti-Spike antibody level; COVID-19 pneumonia; Clinical progression; SARS-CoV-2; Vaccination.

Fig. 1

Patients’ disposition (CONSORT diagram)

Fig. 2

Kaplan–Meier curves for intubation-free survival according to age and anti-S titer in the vaccinated (A, B) and unvaccinated cohort (C, D)

Fig. 3

Predicted probability of clinical progression within 30 days as a function of the Anti-S levels according to the logistic regression model (vaccinated individuals)