Interplay of inflammatory markers and anti-SARS-CoV-2 antibodies in COVID-19 mortality: a prospective cohort study

Objectives Despite high global vaccination coverage, it remains unclear how vaccination and anti-SARS-CoV-2 antibodies affect immune responses and inflammation levels in patients with COVID-19. It is further unclear whether the inflammatory response differs depending on antibody levels and whether the combination of antibody and inflammation levels in COVID-19 patients affects mortality rates. Methods We conducted a prospective multicenter cohort study that included 1031 hospitalized COVID-19 patients from five hospitals. Anti-SARS-CoV-2-spike antibodies, interleukin-6 (IL6) and CRP were measured on hospital admission. The pre-specified endpoint was all-cause in-hospital mortality. Results We observed significantly lower levels of CRP (p<0.001) and IL6 (p<0.001) in patients with antibody levels above 1200BAU/ml. After adjusting for potential confounders, patients with high levels of inflammatory markers (CRP>6mg/dl or IL6>100pg/ml) combined with low levels of anti-SARS-CoV-2-spike antibodies (<1200BAU/ml) were approximately 8 times more likely to die than patients with low inflammatory responses and high antibody levels (CRP: aHR 7.973, 95%CI 2.744-23.169, p<0.001; IL6: aHR 8.973, 95%CI 3.549-22.688, p<0.001). Conclusion Hospitalized COVID-19 patients presenting with high inflammatory markers and low antibody levels exhibited the highest mortality risks. Higher antibody levels are associated with lower levels of inflammation in hospitalized COVID-19 patients.