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Cytokine Blockers May Shield Immune
Inflammation Patients From COVID-19
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Mark Mascolini
People receiving continuous cytokine blockade for immune-mediated inflammatory diseases (IMIDs) had much lower COVID-19 prevalence than people with IMID not receiving cytokines or two other non-IMID control groups in a 2000-person comparison in Germany [1].
Researchers from the University or Erlangen noted that people with IMIDs have immune dysfunctions that may heighten their risk for COVID-19. IMIDs include rheumatoid arthritis, spondyloarthritis, inflammatory bowel disease, and psoriasis. Yet treatment for IMIDs relies on cytokine inhibitors that can control inflammatory cytokines unleashed during SARS-CoV-2 infection. The Erlangen team planned this study to assess prevalence of anti-SARS-CoV-2 immunoglobulin G (IgG) in IMID patients receiving or not receiving cytokine-blocking treatments and in controls without IMID.
Researchers recruited 534 antiinflammatory-treated IMID patients from centers in and around Erlangen in southern Germany. They had to be on stable cytokine inhibitor therapy for more than 3 months. Treatments could include therapeutic antibodies and receptors or chemical agents. The investigators also recruited 259 IMID patients who had not taken cytokine inhibitors within the last 3 months. The research team created two additional control groups: (1) 285 healthcare professionals who care for or study IMID patients and (2) 971 nonhealthcare professionals in the same region already in a cohort designed to study healthy aging or in a cohort of firefighters. No one in these control groups took cytokine inhibitors. Participants gave serum samples between March 18 and April 30, 2020 for testing for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein. Researchers used an in-house ELISA to test for active SARS-CoV-2 infection.
Participants with IMID on continuous cytokines, with IMID not on cytokines, nonhealthcare controls, and healthcare controls averaged 48.9, 55.3, 43.2, and 40.3 years in age. Respective proportions of women were 53.4%, 58.7%, 28.2%, and 66.3%, and respective body mass indexes averaged 26.4, 26.4, 26.5 and 23.6 kg/m2. Respective proportions with chronic lung disease were 8.6%, 6.2%, 6.9%, and 2.5%.
Only 4 of 534 people taking cytokine blockers for IMID had SARS-CoV-2 IgG (0.75%, 95% confidence interval [CI] 0.20 to 1.92), lower than in the IMID no-cytokine blockade group (3.09%, 95% CI 1.33 to 6.09), the healthcare control group (4.21%, 95% CI 2.18 to 7.35) or the nonhealthcare control group (2.27%, 95% CI 1.42 to 3.43). Poisson regression adjusted for age, sex, and sampling date determined that IgG prevalence was significantly higher in healthcare controls than nonhealthcare controls (RR 2.36, 95% CI 1.03 to 5.43, P = 0.043). The same type of analysis determined that IgG prevalence was significantly lower in the IMID on-cytokine blockade group than in the nonhealthcare control group (RR 0.32, 95% CI 0.11 to 0.99, P = 0.048). Among all 46 IgG-positive participants in these 4 groups, only 6 (17%) tested positive for active SARS-CoV-2 infection.
The researchers note that the low prevalence of SARS-CoV-2 IgG in IMID patients taking continuous cytokine inhibitors at first seems counterintuitive because people with IMIDs have an inherently higher risk of SARS-CoV-2 infection and inhibition of proinflammatory cytokines has been linked to increased risk of bacterial and fungal infections. The authors propose two explanations for the low IgG prevalence in the on-cytokine blockade IMIG group:
First, although everyone in this region of Germany was exposed to the same information about social behavior during the COVID-19 pandemic, IMID patients may have followed that advice more stringently. But further analysis showed that "deviation from expected frequencies of social contacts and behavior of IMID patients with and without cytokine inhibitors was very similar," while healthcare controls had higher risk of COVID-19 exposure. Furthermore, since IgG prevalence was similar in the IMID no-cytokine blockade group and nonhealthcare controls, the authors rejected this hypothesis.
Second, the investigators proposed that treatment with cytokine inhibitors "may dampen the inflammatory tissue damage in response to SARS-CoV-2, limit clinical onset of COVID-19 and also inhibit the formation of anti-SARS-CoV-2 antibodies." They believe their findings "support a central pathogenic role of cytokines in COVID-19 and may argue against stopping cytokine inhibitor treatment in patients with IMIDs during the current SARS-CoV-2 pandemic."
Reference
1. Simon D, Tascilar K, Krönke G, et al. Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion. Nat Commun. 2020;11:3774. https://doi.org/10.1038/s41467-020-17703-6
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