Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion

Abstract

Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.

Fig. 1. Prevalence of anti-SARS-CoV-2 IgG antibodies across study groups and validation of the results.

a Left: Prevalence and 95% confidence intervals of a positive anti-SARS-CoV-2 IgG antibody test recognizing the S1 domain of the spike protein in the non-health care (NHC) control cohort, health care (HC) control cohort and immune-mediated inflammatory diseases (IMIDs) with and without cytokine inhibitors (CI); right: risk ratios and 95% confidence intervals of anti-SARS-CoV-2 IgG antibody positivity in the HC control cohort and IMIDs with and without cytokine inhibitors (CI) with the NHC control cohort as reference; b Comparison of anti- SARS-CoV-2 IgG positive (anti-S1+; N = 10) and negative (anti-S1; N = 10) samples (in Euroimmune ELISA) for reactivity in the chemi-luminescent anti- SARS-CoV-2 Spike S1/nucleocapsid IgG test (Yhlo Biotech) and anti-nucleocapsid IgG antibody ELISA (Immundiagnostik Inc). c Validation with in-house ELISA testing reactivities against the S1 domain of the spike protein, the receptor binding domain (RBD) of the S1 domain of the spike protein, extracellular domain (ECD) of the S2 domain of the spike protein and the nucleocapsid in anti- SARS-CoV-2 IgG negative (N = 6) and positive (N = 6) samples (in Euroimmune ELISA), COVID-19 patients with positive viral RNA test (N = 6) and patients with endemic human coronavirus (HCoV) infection (N = 5) in the pre- SARS-CoV-2 time.

Fig. 2. Exposure risk across study groups.

Standardized residuals showing deviation from the expected frequencies for exposure risk variables (contact with persons with a respiratory infection, presence at workplace outside home, travel to risk areas) of IMID patient groups and control groups. A Pearson residual quantifies the individual contribution of each cell in a contingency table to the chi-squared statistic of the table and is calculated by subtracting the expected count in a cell from the observed count and dividing the result by the standard error. A Pearson residual is 0 when the observed cell frequency is equal to the expected and deviates from 0 accordingly as the observed cell frequency is greater or less than the expected count.