Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study.
2020
BACKGROUND: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. METHODS: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. FINDINGS: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0â¢016) and SARS-CoV-2 viral load (p<0â¢001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0â¢35 [95%CI] [0â¢15-0â¢81], log-rank p = 0â¢014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1â¢63 [0â¢35-7â¢7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0â¢35 [0â¢11-0â¢89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3â¢1 [1â¢9-5] for S-IgG; and HR 3â¢0 [1â¢9-4â¢9] for N-IgG; log-rank p<0â¢001 for both). However, no significant differences between groups were found in either S-IgG (HR 1â¢56 [0â¢41-6â¢0]) nor N-IgG (HR 0â¢96 [0â¢26-3â¢5]) responses in an adjusted propensity score analysis. INTERPRETATION: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. FUNDING: Instituto de salud Carlos III (Spain).
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