Emerging Evidence of the Direct Association Between COVID-19 And Chilblains—Reply | JAMA Dermatology | JAMA Network
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Comment & Response
December 23, 2020

Emerging Evidence of the Direct Association Between COVID-19 And Chilblains—Reply

Author Affiliations
  • 1Department of Dermatology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
JAMA Dermatol. 2021;157(2):239-240. doi:10.1001/jamadermatol.2020.4655

In Reply We thank Freeman et al for their comment in reference to our recently published article in JAMA Dermatology.1 The authors rightly point out the limitations of this study in 31 patients with regard to early antibody testing and the imperfect sensitivities and specificities of these tests. However, we later reported updated data, including an additional 23 patients with chilblains.2 In this total series of 54 patients, only 2 had positive serum anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (12.75 and 135.5 AU [absorbance units]/mL, respectively). Moreover, repeated serologic testing 3 weeks after the first (39 patients) ruled out late seroconversion. Therefore, SARS-CoV-2 infection can be excluded with relative certainty, even after accounting for possible lower immunization in mildly symptomatic or asymptomatic patients and for some differences in sensitivity/specificity between the tests used.

Furthermore, it is epidemiologically predictable to find several patients presenting with chilblains with positive anti–SARS-COV-2 antibodies. This has been observed in most series reported,3 but always in a minority of patients, and in our opinion, this is not evidence of an association with coronavirus disease 2019 (COVID-19). In addition, IgA accounts for a non-negligible proportion of positive antibodies, although their sensitivity/specificity is questioned.4

We respectfully disagree with the authors’ suggestion that our series should not have included the 9 patients with a history of chilblains. Given that a direct association has not been formally established nor excluded between chilblains and COVID-19, presuming a priori that chilblains in these patients were not associated with SARS-CoV-2 and thereby excluding them would have introduced a selection bias.

We agree that a considerable body of literature has been published on this subject; however, to our knowledge, no conclusive evidence demonstrates a direct association between chilblains and SARS-CoV-2. We recently commented that positive anti–SARS-CoV/SARS-CoV-2 immunostaining on skin biopsy results of chilblains lack specificity and must be interpreted with caution.5 Moreover, the presence of coronavirus on electron microscopy images has been disputed.5,6

The outbreak of chilblains during the COVID-19 pandemic is a striking coincidence, and an association with the virus initially seemed like a logical conclusion. However, there is current conflicting evidence regarding the pathophysiology of these chilblains, and although the direct involvement of SARS-CoV-2 cannot be formally ruled out, it also cannot be confirmed. Therefore, although the absence of evidence is not the same as evidence of absence, the absence of evidence is also not the same as evidence of the presence of an association between COVID-19 and chilblains.

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Article Information

Corresponding Author: Marie Baeck, MD, PhD, Department of Dermatology, Cliniques Universitaires Saint-Luc (UCL), Avenue Hippocrate 10, B-1200 Brussels, Belgium (marie.baeck@uclouvain.be).

Published Online: December 23, 2020. doi:10.1001/jamadermatol.2020.4655

Conflict of Interest Disclosures: None reported.

References
1.
Herman  A, Peeters  C, Verroken  A,  et al.  Evaluation of chilblains as a manifestation of the COVID-19 pandemic.   JAMA Dermatol. 2020;156(9):998-1003. doi:10.1001/jamadermatol.2020.2368PubMedGoogle ScholarCrossref
2.
Baeck  M, Peeters  C, Herman  A.  Chilblains and COVID-19: further evidence against a causal association.   J Eur Acad Dermatol Venereol. Published online August 31, 2020. doi:10.1111/jdv.16901PubMedGoogle Scholar
3.
Balestri  R, Magnano  M, Rizzoli  L, Rech  G.  Do we have serological evidences that chilblain-like lesions are related to SARS-CoV-2? a review of the literature.   Dermatol Ther. 2020;e14229:e14229. doi:10.1111/dth.14229PubMedGoogle Scholar
4.
Jääskeläinen  AJ, Kuivanen  S, Kekäläinen  E,  et al.  Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation.   J Clin Virol. 2020;129:104512. doi:10.1016/j.jcv.2020.104512PubMedGoogle Scholar
5.
Baeck  M, Hoton  D, Marot  L, Herman  A.  Chilblains and COVID-19: why SARS-CoV-2 endothelial infection is questioned.   Br J Dermatol. Published online August 15, 2020. doi:10.1111/bjd.19489PubMedGoogle Scholar
6.
Brealey  JK, Miller  SE.  SARS-CoV-2 has not been detected directly by electron microscopy in the endothelium of chilblain lesions.   Br J Dermatol. Published online September 30, 2020. doi:10.1111/bjd.19572PubMedGoogle Scholar
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