SARS-CoV-2 neutralizing antibodies decline over one year and patients with severe COVID-19 pneumonia display a unique cytokine profile

Int J Infect Dis. 2021 Nov;112:227-234. doi: 10.1016/j.ijid.2021.09.021. Epub 2021 Sep 15.


Objectives: As coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity.

Methods: This study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups.

Results: Peak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups.

Conclusions: The study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Keywords: COVID-19 disease severity; Cytokine networks; Cytokine storm; Cytokines; Ig titers; Live virus neutralization; Neutralization kinetics; Neutralizing antibodies; Pneumonia; SARS-CoV-2.

MeSH terms

  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • COVID-19* / immunology
  • Cytokines / blood*
  • Humans


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines