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Response to: ‘Correspondence on ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study’’ by De Santis et al
  1. Sofia Ramiro1,2,
  2. Rémy L M Mostard3,
  3. Robert B M Landewé1,4
  1. 1Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, Limburg, The Netherlands
  2. 2Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  3. 3Department of Pulmonology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands
  4. 4Rheumatology & Clinical Immunology, Amsterdam Universitair Medische Centra, Duivendrecht, Noord-Holland, The Netherlands
  1. Correspondence to Dr Sofia Ramiro, Rheumatology, Leiden University Medical Center, 2300 RC Leiden, Zuid-Holland, The Netherlands; sofiaramiro{at}

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We read with interest the letter from De Santis et al1 on our COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome (CHIC) study.2 We thank De Santis et al for sharing their word of caution on the widespread use of glucocorticoids that is indeed very relevant. We totally agree that (at least so far) it has only been demonstrated that patients with severe COVID-19 who need to be hospitalised benefit from treatment with systemic glucocorticoids, either in the form of methylprednisolone or dexamethasone.2 3 As emphasised by De Santis et al, no evidence has been published on the beneficial effect of glucocorticoids in patients with COVID-19, not severely ill and therefore not requiring hospital admission.1 Generalisability of results from previous studies to populations in which glucocorticoids have not been tested should be discouraged. In support of this, De Santi et al share with us their experience with patients presenting at the emergency department who were COVID-19 positive: those treated at home with glucocorticoids had higher odds for requiring admission (OR 26.2, 95% CI 17.3 to 39.8) compared with those not treated with glucocorticoids. Moreover, among the hospitalised patients, mortality did not differ between both groups (ie, with or without glucocorticoids). We totally agree that the prescription of glucocorticoids for patients with COVID-19 should not be generalised and should rather be applied to patients requiring hospital admission and, most likely, even to those showing signs of hyperinflammation like in the COVID-19-associated cytokine storm syndrome. It is namely in the latter group that there is a rationale for immunosuppressive treatment and beneficial results in this group have also shown to be more pronounced.2

In addition, we wonder whether the huge OR of 26 is potentially the (invalid) result of Berkson’s fallacy, or collider bias; the authors only took admitted patients into consideration but are not informed about COVID-19 patients who had or had not used glucocorticoids (exposure) and were not admitted (outcome). Epidemiological reasoning prescribes that you investigate all patients who are at risk of an outcome, and not restrict risk assessments to who have reached the outcome.



  • Handling editor Josef S Smolen

  • Contributors SR drafted the response. All authors reviewed and approved the final response.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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