Are the chilblain‐like lesions observed during the COVID‐19 pandemic due to severe acute respiratory syndrome coronavirus 2? Systematic review and meta‐analysis

Abstract

The expansion of the COVID‐19 pandemic has been accompanied by numerous reports of chilblain‐like lesions (CLL) in different countries; however, the pathogenesis of these lesions is still unclear. This systematic review and meta‐analysis aimed to assess the prevalence of COVID‐19 (diagnosed using PCR and/or serology) in patients with CLL. We undertook a literature search in PubMed, Embase, and Scopus (to 15 March 2021), including studies that reported on the number of patients with CLL with positive PCR and/or serology for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) or with a clinical suspicion of COVID‐19. Regardless of data heterogeneity, a random‐effects model was used to pool prevalence estimates. The meta‐analysis included 63 original studies, involving 2919 cases of CLL. A subgroup of these patients underwent diagnostic tests for COVID‐19 (PCR: n = 1154, 39.5%; serology: n = 943, 32.3%). The pooled prevalence of COVID‐19 in the overall sample and in the subgroup who were tested for COVID‐19 was, respectively: (i) positive PCR: 2.6% [95% confidence interval (CI) 1.9% to 3.4%] and 5.5% (95% CI, 3.7–7.7%); (ii) positive serology for SARS‐CoV‐2: 7.2% (95% CI, 4.7–10.2%) and 11.8% (95% CI, 7.9–16.3%); and (iii) positive PCR and/or serology, 15.2% (95% CI, 10.4–20.7%) and 7.5% (95% CI, 5.1–10.3%). Altogether, a small proportion of diagnostic tests for SARS‐CoV‐2, both PCR and serologies, show positive results in patients with CLL.

COVID-19 pandemic-associated chilblains: more links for SARS-CoV-2 and less evidence for high interferon type I systemic response

“…The role of SARS‐CoV‐2 infection as a trigger of CAC has been widely debated due to the low levels of positive real‐time PCR nasopharyngeal and IgG serologies, which are within the ranges, respectively, of 5·5–13·3% and 7·2–11·8%. 1 , 4 In our series, by using a microneutralization assay for isolated IgA antibodies and serum SARS‐CoV‐2 nucleocapsid antigen detection, we found an overall virological confirmation of SARS‐CoV‐2 infection in 22% of patients, including 32% in children. This latter result is consistent with the frequency of 30–37% of seroconversion observed in previous series of children with asymptomatic and/or mild SARS‐CoV‐2 infection during the acute and convalescent periods, 5 , 6 adding new arguments for a causative role of SARS‐CoV‐2 in CAC.…”

“…In our series, the characteristics of CAC, including an overall balanced sex ratio, predominance of patients with low BMI, and clinical presentation and outcome, were broadly similar to those previously described. 1 , 3 We found significant high frequencies of Raynaud phenomenon, BASCULE syndrome and subungual splinter haemorrhages, possibly explained by the prospective study design and an absence of clinical details in some of the large series.…”

“…Since the onset of the SARS‐CoV‐2 pandemic, the direct causative role of the virus in COVID‐19‐associated chilblains (CAC) has remained under question due to the low rate of positivity to SARS‐CoV‐2 nasopharyngeal polymerase chain reaction (PCR) and blood serology. 1 Likewise, the suspected pivotal pathogenic role of upregulation of interferon type I (IFN‐I) is mainly indirectly supported by assessment of in situ immune response. 2 …”

Chilblain-Like Lesions (CLL) Coinciding With the SARS-CoV-2 Pandemic in Children: A Systematic Review

“…13,20,30 CLL may be provoked by behavioral changes brought on by lockdowns and quarantines; specifically, altered peripheral circulation secondary to sedentary behaviors and inadequate coverage of hands and feet when exposed to cold interior environments. 23,[31][32][33] Improvements in CLL cases following thermal protection measures and the relaxation of confinement restrictions give some support for behavioral hypotheses. 23,[34][35][36] Additionally, caregivers and children in isolation may have had greater opportunity to observe these cutaneous changes than if normal work and educational activity were permitted.…”

“…23,[31][32][33] Improvements in CLL cases following thermal protection measures and the relaxation of confinement restrictions give some support for behavioral hypotheses. 23,[34][35][36] Additionally, caregivers and children in isolation may have had greater opportunity to observe these cutaneous changes than if normal work and educational activity were permitted. 32 Finally, the increased media attention to COVID toes may have led to increased care-seeking by patients with chilblains during the pandemic.…”