Seroconversion in septic ICU patients presenting with COVID-19: necessary but not sufficient

Abstract

Background: As COVID-19 pandemic and vaccination effects progress, research now focuses on adaptive immunological response to SARS-CoV-2. Few studies specifically investigated intensive care unit (ICU) patients, and little is known about kinetics of humoral response in such critically ill patients. In this context, the main objective of the present work was to perform a longitudinal analysis of the humoral response in critically ill COVID-19 patients with prolonged ICU stays in regard with initial inflammatory response, disease severity and mortality.

Methods: Over a 3 week period, circulating immunoglobulins (Ig) against SARS-CoV-2 along with several immunological and clinical parameters were measured in 64 ICU COVID-19 patients.

Results: Critically ill COVID-19 patients mounted a dynamic and sustained antibody response of both IgM and IgG as soon as the first day of ICU hospitalization. This serological response was not associated with any of the classical immunological parameters measured at ICU admission or with initial severity clinical scores. IgM and IgG levels and seroconversion trajectories were not associated with unfavourable outcome.

Conclusion: Despite rapid seroconversion and elevated humoral response, COVID-19 patients are still characterized by elevated mortality. Additional studies, including cytotoxic T cell functions, are mandatory to understand the immunological mechanisms contributing to long stay of COVID-19 patients in ICU.

Keywords: COVID-19; IFN-γ; immunosuppression; lymphocyte; sepsis; seroconversion.

Figure 1

Longitudinal characterization of humoral response in 64 critically ill COVID-19 patients. Over time evolution of IgM (left panel) and IgG (right panel) levels (VidasⓇ index) are depicted during the first month after admission. Results are presented as individual data and boxplots.

Figure 2

ICU admission Ig titres according to elapsed time from first symptoms in 64 critically ill COVID-19 patients. IgM (left panel) and IgG (right panel) levels (VidasⓇ index) are presented as box plots according to delay between first clinical symptoms and ICU admission (days presented as quartiles). IFN-α concentrations at ICU admission (median values, red line) are similarly plotted according to delay between first clinical symptoms and ICU admission (red scale on right part of both histograms).

Figure 3

IgG titres association with SOFA score and mortality at day 28. A. SOFA. IgG titre kinetics (VidasⓇ index) are presented as box plots depending on admission SOFA score (stratified by quartiles). Colour boxes represent the different sample timing from 0–20 d after admission. B. Mortality. IgG titre (VidasⓇ index) are presented as box plots during the first month after admission according to mortality assessed at day 28.