Commentary: Cytokine inhibitors have a low prevalence of SARS-CoV-2 seroconversion

COMMENTARY

Do Biologics Protect Against COVID-19 Infection?

In a recent publication in Nature Communications¹ a team from Friedrich-Alexander University in Germany described their findings from a cross-sectional population cohort study on the prevalence of anti-SARS-CoV-2 immunoglobulin G (IgG) in patients with chronic immune-mediated inflammatory diseases (IMIDs) on cytokine-blocking treatments.  This patient cohort was compared against subjects with IMIDs, not on cytokine inhibitors, health care workers, and healthy controls.   The findings from this study showed that patients with IMID on cytokine inhibitors had a lower prevalence of anti-SARS-CoV-2 IgG response compared to the other three cohorts.  To assess whether this could be accounted for by differences in social exposure between the groups, the investigators assessed exposure risk variables in the four groups and found those to be similar between the two IMID groups and less than that of health care workers.  These findings led the authors to conclude that patients with IMIDs on cytokine inhibitor therapies have reduced susceptibility to SARS-CoV2 infection compared with patients not receiving cytokine-inhibitors, as well as the general population.

While these findings are highly intriguing, they have to be taken with caution.  Thus, while the findings described here are significant, they are based on very small sample sizes and lack validation from an independent cohort.  Furthermore, using a survey to control for exposure is likely inadequate as it may not capture subtle changes in behavior that are not easily caught on survey questionnaires.  In addition, while these treatments inhibit specific inflammatory pathways and may be protective against more severe COVID-19², it is hard to envision how they’d prevent seroconversion of exposed patients.  This is supported by studies showing blunted, but not absent, vaccination responses to influenza vaccine³.  Lastly, if the implications of this study hold true, it would also have potential implications regarding the utility of vaccinating patients for COVID while on biologics.

In summary, while these findings are intriguing, the message from this paper that patients with IMIDs on biologics are protected against COVID-19 infection has to be taken with great caution. More extensive and robust studies are required before we can confidently determine that biologics protect against SARS-CoV-2 infection.

Reference:

1. Simon D, et al.  Nat Communications 2020, 3774
2. Winthrop KL, et al.  Ann Rheum Disease, 2021 80(2):269-271
3. Gelinck LBS, et al.  Ann Rheum Dis 2008, 67(5):713-6.