Skip to main content
PLOS Global Public Health logoLink to PLOS Global Public Health
. 2022 Oct 19;2(10):e0000488. doi: 10.1371/journal.pgph.0000488

Snotwatch COVID-toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia

Rana Sawires 1,2,*, Christopher Pearce 3, Michael Fahey 4,5, Hazel Clothier 2,6,7, Karina Gardner 3, Jim Buttery 1,2,7
Editor: Kevin Escandón8
PMCID: PMC10022016  PMID: 36962522

Abstract

The COVID-19 pandemic has caused widespread illness with varying clinical manifestations. One less-commonly-reported presentation of COVID-19 infection is chilblain-like lesions. We conducted an ecological analysis of chilblain presentations in comparison with confirmed and suspected COVID-19 infections in a primary care setting to establish that a relationship exists between the two. Our study collated data from three Primary Health Networks across Victoria, Australia, from 2017–2021, to understand patterns of chilblain presentations prior to and throughout the pandemic. Using a zero-inflated negative binomial regression analysis, we estimated the relationship between local minimum temperature, COVID-19 infections and the frequency of chilblain presentations. We found a 5.72 risk ratio of chilblain incidence in relation to COVID-19 infections and a 3.23 risk ratio associated with suspected COVID-19 infections. COVID-19 infections were also more strongly associated with chilblain presentations in 0-16-year-olds throughout the pandemic in Victoria. Our study statistically suggests that chilblains are significantly associated with COVID-19 infections in a primary care setting. This has major implications for clinicians aiming to diagnose COVID-19 infections or determine the cause of a presentation of chilblains. Additionally, we demonstrate the utility of large-scale primary care data in identifying an uncommon manifestation of COVID-19 infections, which will be significantly beneficial to treating physicians.

Introduction

The global coronavirus disease-19 (COVID-19) pandemic caused widespread illness and global economic disruption. In addition to the more common respiratory symptoms, cutaneous manifestations were reported in some patients with COVID-19 [1, 2] particularly chilblain-like skin changes [35]. Chilblains are an inflammatory dermatological condition affecting the acral regions of the body, often affecting women and middle-aged adults [6]. They present more frequently in wet-weather seasons, such as late winter and early spring [6] and are caused by abnormal vasospasm in response to cold associated with an inflammatory infiltrate composed of T cells, B cells and macrophages [6]. Until COVID-19, infectious causes were not thought to be an association [7].

Finding a strong link between COVID-19 and chilblains has proven elusive. While an international register of people with skin eruptions revealed 45% of 505 patients had respiratory symptoms consistent with COVID-19 [8], other studies found no serological evidence of COVID-19 infection in people with chilblains [9]. Given the difficulty synthesising these contradictory findings, we aimed to establish and quantify the temporal relationship of chilblains with COVID-19 in Victoria, Australia in an ecological framework. Using such a large dataset lays the groundwork for future research and has substantial public health and epidemiological implications for tracking COVID-19 viral spread in the community.

Methods

Data collection

Data were extracted using the POLAR (POpulation Level Analysis and Reporting) analytics program developed by Outcome Health. The POLAR system collects and processes data from constituent practices across Primary Health Networks (PHNs). PHNs contributing to this study are located in Eastern Victoria (Eastern Melbourne, Gippsland and South-Eastern Melbourne) representing 537 general practices with a pooled catchment of 3.65 million patients (Fig 1). POLAR is an end-to-end analytics platform that collects and processes electronic medical record information from general practices on behalf of PHNs. POLAR is both a patient-level clinical decision support tool and a population health analytics platform. Practices contributing data via the POLAR platform can engage in research activity by agreeing to share de-identified snapshots of their data for ethics-reviewed, PHN-approved research. Data collected by the POLAR system and shared for research is processed, mapped, coded (to SNOMED codes), curated and redacted according to POLAR’s Data De-identification Decision-Making Framework (developed with guidance from the Office of the Australian Information Commissioner). This yields a longitudinal dataset stripped of identifiable information.

Fig 1. Data was obtained from three Primary Health Networks, servicing 3.65 million people in Victoria, Australia 2017–2021 (blue).

Fig 1

Base map obtained from: https://www.arcgis.com/home/item.html?id=1970c1995b8f44749f4b9b6e81b5ba45.

Study design and cohort

Using data collected from participating General Practices (GPs) on behalf of PHNs, we conducted a retrospective ecologic cohort analysis from January 2017- September 2021. Inclusion criteria were any diagnoses of chilblains, COVID-19 disorder, or suspected COVID-19 disorder recorded in any Victorian general practice located in one of the three participating PHNs. SNOMED codes [10] are an organised set of medical terms which provide codes, synonyms and definitions for terms used in clinical documentation and reporting and are used for organising data collected by POLAR. Our study cohort was generated using SNOMED codes for conditions of interest: chilblains (SNOMED code 37869000), COVID-19 disorder (SNOMED code 840539006), and suspected COVID-19 (SNOMED code 840544004). Data extracted included: the patient’s age in years and the date of diagnosis. Data were de-identified. COVID-19 disorder is a code used for patients who have had a positive polymerase chain reaction (PCR) test for COVID-19 infection and recorded in the GP software. Suspected COVID-19 codes are used for symptomatic patients who have not had a positive PCR test for COVID-19 infection.

Additionally, we obtained local daily minimum temperature data from all weather stations in Victoria from the Bureau of Meteorology (BOM) from January 2017- September 2021 and aggregated these data across the state. This yielded average statewide minimum temperature data.

All data were then aggregated by the week of the year, where the weeks were calculated from Monday to Sunday. The first and last weeks of the year were included independently regardless of the day of the week they started or ended, respectively.

Statistical analysis

The coding program, R (version 4.0.2) [11], was applied through RStudio (version 1.2.5) [12] for statistical analysis of temporal data. Following fit testing of the distribution of our data, we determined that conducting a zero-inflated negative binomial regression analysis would be the most suitable technique for modelling our data. We created a multivariate model, which used weekly minimum temperature, COVID-19 and suspected COVID-19 diagnoses to predict chilblains. To meaningfully determine the effect of temperature on chilblains, we used a negative transformation of the temperature data.

Additionally, to assess the possible lag in any association between chilblains and the COVID-19 diagnoses, we created lead and lag models for our datasets, eight exploring leads in chilblains diagnoses, and eight exploring lags. We assessed the relationship between COVID-19 and chilblains in different age groups (0–16 years, 17–49 years, and 50 years and over). To assess the effect of COVID-19 diagnoses on chilblains presentations we compared the risk of chilblains when COVID-19 diagnoses were present at or above the 95th percentile of their maximum rate to the 50th centile of their maximum rate. Our significance level was set at p<0.01.

Ethics approval

All data were full anonymized before they were accessed for this study. Ethical approval for Snotwatch projects was obtained through our primary Human Research Ethics Committee (HREC) in Monash Health from 24th July 2019 (NMA/ERM Reference Number: 53611).

For the use of data from POLAR GP, additional approval was obtained under Monash Health (Monash Health Reference Number: RES-18-0000-232A, NMA HREC Reference Number: HREC/18/MonH/345).

The extraction, storage and management of data on the POLAR platform has ethics approval from the RACGP National Research and Evaluation Research Committee (Protocol ID: 17–008). Ethics approval for this project was granted by the Monash Health Human Research Ethics Committee (Ref No: 21-013L).

Results

Cohort demographics

From January 2017-September 2021, there were a total of 6,846 chilblains diagnoses across the three participating PHNs in Victoria. The distribution of chilblains across the age groups approximately matched that of the Victorian population.

A total of 3,687 diagnoses of COVID-19 disorders and 4,688 diagnoses of suspected COVID-19 were recorded in a GP setting from January 2020- September 2021. We excluded four diagnoses of COVID-19 disorder and one diagnosis of suspected COVID-19 disorder that occurred before January 2020 as these were assumed to be errors in the system. These exclusions are unlikely to alter the findings of our study.

Bureau of meteorology temperature data

Victoria is a region with a moderate climate in the Southern Hemisphere. We obtained aggregated data for minimum temperature across the state of Victoria from the Bureau of Meteorology. The median minimum temperature for Victoria was 8.12 degrees Celsius (Interquartile Range 5.53–12.08). The minimum and maximum temperatures for each year remained consistent, with only a slightly lower maximum temperature in 2021, which is likely because the data ended in September, prior to the beginning of the 2021 summer season.

Data visualisation

A clear peak of chilblains presentations was evident in winter of each year. This coincided with decreasing temperature throughout the 5-year period. COVID-19 disorder, and suspected COVID-19 disorder mirrored the peak in chilblains in 2020 very closely but lagged the chilblains peak in 2021 (Fig 2).

Fig 2. Weekly number of chilblains diagnoses, COVID-19 diagnoses and minimum temperature in Victoria 2017–2021.

Fig 2

Associations of chilblains with COVID-19 diagnoses and average minimum temperature

In Victoria, chilblains were significantly associated with a reduction in temperature, having a risk ratio (RR) of 1.33 (99%CI 1.27–1.40) per 1°Celcius. When comparing the 95th centile to 50th centile of COVID-19 and suspected COVID-19 diagnoses, there was a 5.72 RR (99%CI 2.27–14.44) and 3.23 RR (99%CI 1.32–7.91) of chilblains presentations respectively. A secondary model was created using only temperature as a predictor of chilblains presentations. This model showed a risk ratio of 1.37 per 1°Celcius. However, using vuong z-statistics, this model was deemed inferior to the model including COVID diagnoses as covariates. Lead and lag analyses did not demonstrate any meaningful temporal associations between chilblains and COVID-19 in a general practice setting. The complete table is shown in S1 File.

Both COVID-19 diagnosis and suspected COVID-19 also had a greater association with chilblains in 0-16-year-old children with chilblains (5.96 RR and 4.34 RR respectively). The size of the association reduced with each age group, with only a 3.03 RR and 1.69 RR respectively with chilblains in people 50 years and over. The results from our subgroup analyses are shown in Table 1.

Table 1. Associations between COVID-19 disorder, suspected COVID-19 disorder and decreasing temperature with chilblains in different age groups.

All results were statistically significant.

RR+ OF CHILBLAINS ALL COHORT (99% CI++) RR+ OF CHILBLAINS IN 0–16-YEAR-OLDS (99% CI++) RR+ OF CHILBLAINS IN 17–49-YEAR-OLDS (99% CI++) RR+ OF CHILBLAINS IN 50 YEARS AND OVER (99% CI++)
COVID-19 DISORDER 5.72 (2.27–14.44) 5.96 (1.68–21.18) 4.98 (2.00–12.38) 3.03 (1.42–6.46)
SUSPECTED COVID-19 3.23 (1.32–7.91) 4.34 (1.31–14.32) 3.59 (1.49–8.68) 1.69 (0.84–3.40)
DECREASING TEMPERATURE (PER 1°C) 1.33 (1.27–1.40) 1.27 (1.15–1.41) 1.32 (1.24–1.40) 1.29 (1.23–1.36)

+RR: Risk Ratio

++ CI: Confidence Interval

Discussion

To our knowledge, this is the largest population-level ecological study of the relationship between COVID-19 and presentations of chilblains in a GP setting. We found increases in diagnoses of chilblains in participating PHNs that could be significantly correlated with COVID-19 circulation in Victoria. Modelling using only temperature as a predictor of chilblains was insufficient and COVID-19 diagnoses were required to explain the increase in chilblains throughout the pandemic. Our study confirms findings in most of the existing literature. Since the beginning of 2020, chilblains have been reported in conjunction with COVID-19 disorder in several European case series and one epidemiological study in California [3, 4, 13]. Nevertheless, it is still uncertain whether COVID-19 infection is the cause of these presentations. While in some cases, a causal relationship has been supported by positive PCR results [4, 14] or serology [15], the vast majority of studies show a low rate of PCR positivity for COVID-19 diagnoses in patients who present with chilblains [16, 17].

The mechanism of chilblains presentations in COVID-19 infectious is unknown. One systematic review showed that the cutaneous manifestations of COVID-19 infection could be due to increased ACE2 expressions in the skin, although the specific method of erythema development in COVID-19 infection remains unclear [18].

Additionally, there is uncertainty surrounding the diagnosis of cutaneous manifestations of COVID-19 infections. Histological confirmation of chilblains diagnosis requires a skin biopsy that demonstrates a superficial and deep lymphocytic inflammatory infiltrate in a lichenoid, perivascular, and peri-eccrine distribution [19]. However, there is no consensus on whether chilblains in the context of COVID-19 infections have the same histological features as idiopathic chilblains [15].

In light of the difficulty in delineating the pathophysiological association between COVID-19 infection and chilblains, it has been suggested that behaviour changes during lockdowns, such as not wearing shoes or socks in the home, leaving extremities more exposed to the cold, could explain the possible increase in the number of chilblains presentations over the course of the pandemic [20]. One explanation is that in response to COVID-19 infection, a high level of type I interferons (IFN) (as seen in familial chilblains lupus) could itself be the cause for the development of chilblains [21]. Further research is required to ascertain whether this is the case.

Our findings showed that COVID-19 disorder diagnoses were most strongly associated with chilblains presentations in the same week, whereas suspected COVID-19 disorder was associated with chilblains presentations in the preceding and following weeks more strongly. See S1 File.

Studies have suggested that various cutaneous manifestations of COVID-19 can precede, lag or coincide with extracutaneous symptoms of COVID-19 infection or a confirmed COVID-19 diagnosis [2]. More specifically, chilblain-like lesions are the latest to present, with a 2-8-week lag following respiratory COVID-19 symptoms [5, 15].

Chilblains may also be a late manifestation of the disease and PCR testing could yield negative by the time of assessment due to a reduced viral load [1]. A survey of eight paediatric patients showed an average of 19.6 days delay between chilblains symptom onset and visiting a dermatology clinic [12], and a case series spanning 8 countries, showed that chilblains lasted a median of 14 days [8]. By contrast, it has been reported that in subgroups of patients with COVID-19-associated-chilblains, PCR results were positive at day 8 of testing but became negative by day 14 [22]. Thus, these factors could explain the low rates of positive PCR findings demonstrated in a number of studies [4, 14].

Despite this, our study still showed an association between confirmed COVID-19 cases and chilblains in the same week, and no statistically significant associations were found when delays between chilblains and COVID-19 disorder was analysed. This could be explained by the widespread use of telehealth during the pandemic which would have meant that chilblains diagnoses temporally coincided with COVID-19 infections [23]. Nevertheless, time delays in association with suspected COVID were found and further investigation is needed to ascertain whether COVID-19 infection plays a role in the development of chilblains.

In addition to a high proportion of chilblains in our paediatric age group (18.7%), a key finding of our study was that the association of COVID-19 infection was greatest with chilblains presentations in 0–16-year-old children. Analysis of the proportion of 0-16-year-old patients in our cohort showed that it was consistent with the proportion of 0-16-year-olds in Victoria, Australia. Additionally, a number of reports have shown reduced utilisation of paediatric healthcare services throughout the pandemic [2426]. Thus, these findings could not be attributed to over-representation of this age group. Nevertheless, this finding is not without an important caveat. Given the large confidence intervals for our subgroup analyses and the overlap in these intervals across the three age groups, there may not in fact be a difference in the strength of the associations between chilblains and COVID-19 based on age. However, in support of this finding, chilblain-like lesions in the context of COVID-19 disease have been more commonly reported in teenagers and young adults [1, 2, 8, 20]. Paediatric patients with chilblains often lack respiratory symptoms [13] and have a low rate of positive PCR for COVID-19 infection [15, 27]. It has been proposed that children and young adults have a more robust innate immune response leading to reduced viral load and negative PCR tests.[19, 20]. These findings stand in contrast to idiopathic chilblains which are historically more common in middle-aged people [7] and very rarely reported in children [28]. This may imply that chilblain-like lesions in COVID-19 have a different pathophysiology from idiopathic chilblains and requires further investigation.

The key advantage of our study compared to existing literature is that our ecological study design yields a significant sample size. This adds significant power to our analysis and the findings of our study. One Canadian study also demonstrated that among children who presented with acral lesions throughout the COVID-19 pandemic, there was a large proportion of household contacts with COVID-19 infections, irrespective of whether the child also had a COVID-19 infection [29]. This suggests an association between COVID-19 and skin manifestations that may not be easily demonstrated at an individual level. As such, an ecological analysis of this phenomenon may be the best approach to assess the relationship between COVID-19 and chilblains presentations. This study design also enabled us to meaningfully analyse whether leads and lags existed between the timing of our diagnoses. Decreasing temperature is a key cause of chilblains presentations and our study accounted for this by including these data in our analysis. This means that the increase in chilblains presentations in 2020 and 2021 could be more reliably associated with COVID-19. Additionally, the low p-value for significance in our study gives greater confidence in the strength of our associations.

Nevertheless, there are some key limitations to our dataset. Over the course of the pandemic, most COVID-19 diagnoses in Victoria were not made in a GP setting. As such, our chilblains diagnosis data are only a subset of all COVID-19 infections that occurred in the last two years. There is also uncertainty around how general practitioners coded COVID-19 diagnoses and whether there was a time delay between a patient having a confirmed COVID-19 infection and their general practice visit at which this diagnosis would have been recorded. We included suspected COVID-19 diagnosis in our analysis for completion, but this is an unreliable measure of COVID-19 infection in the state and may not accurately represent circulation of COVID-19 infections in Victoria. An additional factor to consider is that a significant proportion of cases in Victoria were diagnosed through state-run testing hubs with minimal notification back to GPs. This may have skewed our results and masked possible lead and lag associations between chilblains and COVID-19.

Ultimately, the ecological analysis conducted in this study means that we can only demonstrate associations between our datasets, and a causal relationship between COVID-19 infection and chilblains presentations cannot be confirmed. Nevertheless, our findings lay the foundation for future research which may confirm a causal relationship, as well as ascertain the pathophysiology and aetiology of chilblains due to COVID-19 infection.

Conclusion

Our Victorian ecological study of chilblains and COVID-19 showed a significant association between these presentations in Victorian general practices during the first two years of the COVID-19 pandemic. Using novel statistical methodology, our study can inform epidemiological understanding of COVID-19 circulation in a given region and population. Additionally, existing research to ascertain the causal relationship between the novel coronavirus and chilblains is scant. However, the size of association found in our study demonstrates that further investigation is warranted.

These findings have demonstrated the potential of using large-scale primary care data for increasing clinician awareness of the potential for chilblains in patients with COVID-19 infections. Future directions may include investigating whether chilblains presentations are a reliable surrogate measure of the spread of COVID-19 infections.

Supporting information

S1 File. Appendix A: Chilblains, COVID-19 disorder and suspected COVID-19 disorder lead and lag analysis results.

Table A: COVID-19, suspected COVID-19 and temperature associations with chilblains with leads and lags.

(DOCX)

Data Availability

PHNs have data sharing agreements including research with constituent general practices and provide them with a data analytics and reporting service in the areas of clinical, business, accreditation, and quality improvement. PHNs are the owner of the de-identified GP data collected from general practices and have provided permission to their contracted data custodian Outcome Health to supply a defined subset of this GP data to the project through the POpulation Level Analysis and Reporting (POLAR) platform, developed and deployed by Outcome Health. Research requests are processed through the Aurora Primary Care Research Institute. The subset of the de-identified GP data was sourced from 537 general practices and was used to contribute to advancing the evidence base by sharing de-identified, patient level data for ethics-reviewed, translational research. Data for this study can be made available through contacting Outcome Health via admin@outcomehealth.org.au.

Funding Statement

Funding for this project was provided by the Royal Children’s Hospital Foundation. J.B. received the grant. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

References

  • 1.Galvan Casas C, Catala A, Carretero Hernandez G, Rodriguez-Jimenez P, Fernandez-Nieto D, Rodriguez-Villa Lario A, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020;183(1):71–7. Epub 2020/04/30. doi: 10.1111/bjd.19163 ; PubMed Central PMCID: PMC7267236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Daneshgaran G, Dubin DP, Gould DJ. Cutaneous Manifestations of COVID-19: An Evidence-Based Review. Am J Clin Dermatol. 2020;21(5):627–39. Epub 2020/09/01. doi: 10.1007/s40257-020-00558-4 ; PubMed Central PMCID: PMC7456663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. Chilblain-like lesions on feet and hands during the COVID-19 Pandemic. Int J Dermatol. 2020;59(6):739–43. Epub 2020/04/25. doi: 10.1111/ijd.14937 ; PubMed Central PMCID: PMC7264591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.McCleskey PE, Zimmerman B, Lieberman A, Liu L, Chen C, Gorouhi F, et al. Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic. JAMA Dermatol. 2021;157(8):947–53. Epub 2021/06/24. doi: 10.1001/jamadermatol.2021.2120 ; PubMed Central PMCID: PMC8223123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Kashetsky N, Mukovozov IM, Bergman J. Chilblain-Like Lesions (CLL) Associated With COVID-19 ("COVID Toes"): A Systematic Review. J Cutan Med Surg. 2021:12034754211004575. Epub 2021/04/15. doi: 10.1177/12034754211004575 . [DOI] [PubMed] [Google Scholar]
  • 6.Nyssen A, Benhadou F, Magnee M, Andre J, Koopmansch C, Wautrecht JC. Chilblains. Vasa. 2020;49(2):133–40. Epub 2019/12/07. doi: 10.1024/0301-1526/a000838 . [DOI] [PubMed] [Google Scholar]
  • 7.Cappel JA, Wetter DA. Clinical characteristics, etiologic associations, laboratory findings, treatment, and proposal of diagnostic criteria of pernio (chilblains) in a series of 104 patients at Mayo Clinic, 2000 to 2011. Mayo Clin Proc. 2014;89(2):207–15. Epub 2014/02/04. doi: 10.1016/j.mayocp.2013.09.020 . [DOI] [PubMed] [Google Scholar]
  • 8.Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Takeshita J, et al. Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries. J Am Acad Dermatol. 2020;83(2):486–92. Epub 2020/06/02. doi: 10.1016/j.jaad.2020.05.109 ; PubMed Central PMCID: PMC7260509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.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;33(6):e14229. Epub 2020/08/28. doi: 10.1111/dth.14229 ; PubMed Central PMCID: PMC7460996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Organisation IHTSD. SNOMED International: International Health Terminology Standards Development Organisation 2021. [cited 2021]. Available from: https://www.snomed.org/. [Google Scholar]
  • 11.R Development Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2010. [Google Scholar]
  • 12.RStudio Team. RStudio: Integrated Development Environment for R. Boston, MA: 2015. [Google Scholar]
  • 13.Garcia-Lara G, Linares-Gonzalez L, Rodenas-Herranz T, Ruiz-Villaverde R. Chilblain-like lesions in pediatrics dermatological outpatients during the COVID-19 outbreak. Dermatol Ther. 2020;33(5):e13516. Epub 2020/05/08. doi: 10.1111/dth.13516 ; PubMed Central PMCID: PMC7261972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Recalcati S, Fantini F. Chilblain-like lesions during the COVID-19 pandemic: early or late sign? Int J Dermatol. 2020;59(8):e268–e9. Epub 2020/06/24. doi: 10.1111/ijd.14975 ; PubMed Central PMCID: PMC7361425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.El Hachem M, Diociaiuti A, Concato C, Carsetti R, Carnevale C, Ciofi Degli Atti M, et al. A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection. J Eur Acad Dermatol Venereol. 2020;34(11):2620–9. Epub 2020/06/01. doi: 10.1111/jdv.16682 ; PubMed Central PMCID: PMC7301001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Gisondi P, S PI, Bordin C, Alaibac M, Girolomoni G, Naldi L. Cutaneous manifestations of SARS-CoV-2 infection: a clinical update. J Eur Acad Dermatol Venereol. 2020;34(11):2499–504. Epub 2020/06/26. doi: 10.1111/jdv.16774 ; PubMed Central PMCID: PMC7362144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Piccolo V, Neri I, Filippeschi C, Oranges T, Argenziano G, Battarra VC, et al. Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients. J Eur Acad Dermatol Venereol. 2020;34(7):e291–e3. Epub 2020/04/25. doi: 10.1111/jdv.16526 ; PubMed Central PMCID: PMC7267498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Zhao Q, Fang X, Pang Z, Zhang B, Liu H, Zhang F. COVID-19 and cutaneous manifestations: a systematic review. J Eur Acad Dermatol Venereol. 2020;34(11):2505–10. Epub 2020/07/01. doi: 10.1111/jdv.16778 ; PubMed Central PMCID: PMC7361780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Cappel MA, Cappel JA, Wetter DA. Pernio (Chilblains), SARS-CoV-2, and COVID Toes Unified Through Cutaneous and Systemic Mechanisms. Mayo Clin Proc. 2021;96(4):989–1005. Epub 2021/03/15. doi: 10.1016/j.mayocp.2021.01.009 ; PubMed Central PMCID: PMC7826004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Neri I, Virdi A, Corsini I, Guglielmo A, Lazzarotto T, Gabrielli L, et al. Major cluster of paediatric ’true’ primary chilblains during the COVID-19 pandemic: a consequence of lifestyle changes due to lockdown. J Eur Acad Dermatol Venereol. 2020;34(11):2630–5. Epub 2020/06/14. doi: 10.1111/jdv.16751 ; PubMed Central PMCID: PMC7323208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Damsky W, Peterson D, King B. When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection. J Am Acad Dermatol. 2020;83(3):e269–e70. Epub 2020/06/23. doi: 10.1016/j.jaad.2020.06.052 ; PubMed Central PMCID: PMC7303035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Freeman EE, McMahon DE, Hruza GJ, Lipoff JB, French LE, Fox LP, et al. Timing of PCR and antibody testing in patients with COVID-19-associated dermatologic manifestations. J Am Acad Dermatol. 2021;84(2):505–7. Epub 2020/09/14. doi: 10.1016/j.jaad.2020.09.007 ; PubMed Central PMCID: PMC7482613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Snoswell CL, Caffery LJ, Haydon HM, Thomas EE, Smith AC. Telehealth uptake in general practice as a result of the coronavirus (COVID-19) pandemic. Aust Health Rev. 2020;44(5):737–40. Epub 2020/08/28. doi: 10.1071/AH20183 . [DOI] [PubMed] [Google Scholar]
  • 24.Isba R, Edge R, Jenner R, Broughton E, Francis N, Butler J. Where have all the children gone? Decreases in paediatric emergency department attendances at the start of the COVID-19 pandemic of 2020. Arch Dis Child. 2020;105(7):704. Epub 2020/05/08. doi: 10.1136/archdischild-2020-319385 . [DOI] [PubMed] [Google Scholar]
  • 25.Dopfer C, Wetzke M, Zychlinsky Scharff A, Mueller F, Dressler F, Baumann U, et al. COVID-19 related reduction in pediatric emergency healthcare utilization—a concerning trend. BMC Pediatr. 2020;20(1):427. Epub 2020/09/08. doi: 10.1186/s12887-020-02303-6 ; PubMed Central PMCID: PMC7475725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hu N, Nassar N, Shrapnel J, Perkes I, Hodgins M, O’Leary F, et al. The impact of the COVID-19 pandemic on paediatric health service use within one year after the first pandemic outbreak in New South Wales Australia—a time series analysis. Lancet Reg Health West Pac. 2022;19:100311. Epub 2021/11/09. doi: 10.1016/j.lanwpc.2021.100311 ; PubMed Central PMCID: PMC8564784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Hubiche T, Cardot-Leccia N, Le Duff F, Seitz-Polski B, Giordana P, Chiaverini C, et al. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatol. 2021;157(2):202–6. Epub 2020/11/26. doi: 10.1001/jamadermatol.2020.4324 ; PubMed Central PMCID: PMC7689569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Simon TD, Soep JB, Hollister JR. Pernio in pediatrics. Pediatrics. 2005;116(3):e472–5. Epub 2005/09/06. doi: 10.1542/peds.2004-2681 . [DOI] [PubMed] [Google Scholar]
  • 29.Hubiche T, Phan A, Leducq S, Rapp J, Fertitta L, Aubert H, et al. Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters. Ann Dermatol Venereol. 2021;148(2):94–100. Epub 2021/02/09. doi: 10.1016/j.annder.2020.11.005 ; PubMed Central PMCID: PMC7831537. [DOI] [PMC free article] [PubMed] [Google Scholar]
PLOS Glob Public Health. doi: 10.1371/journal.pgph.0000488.r001

Decision Letter 0

Kevin Escandón

23 Aug 2022

PGPH-D-22-00669

Snotwatch COVID-Toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia

PLOS Global Public Health

Dear Dr. Sawires,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 07 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Kevin Escandón, MD, MSc

Academic Editor

PLOS Global Public Health

Journal Requirements:

1. In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records/samples used in your retrospective study. Specifically, please ensure that you have discussed whether all data/samples were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data/samples from their medical records used in research, please include this information.

2. Please amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

a. Please clarify all sources of funding (financial or material support) for your study. List the grants (with grant number) or organizations (with url) that supported your study, including funding received from your institution. 

b. State the initials, alongside each funding source, of each author to receive each grant.

c. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

d. If any authors received a salary from any of your funders, please state which authors and which funders.

3. Please ensure that your Financial disclosure statement is matched with the funding information.

4. Figure 1.png: please (a) provide a direct link to the base layer of the map (i.e., the country or region border shape) and ensure this is also included in the figure legend; and (b) provide a link to the terms of use / license information for the base layer image or shapefile. We cannot publish proprietary or copyrighted maps (e.g. Google Maps, Mapquest) and the terms of use for your map base layer must be compatible with our CC-BY 4.0 license. 

Note: if you created the map in a software program like R or ArcGIS, please locate and indicate the source of the basemap shapefile onto which data has been plotted.

If your map was obtained from a copyrighted source please amend the figure so that the base map used is from an openly available source. Alternatively, please provide explicit written permission from the copyright holder granting you the right to publish the material under our CC-BY 4.0 license.

Please note that the following CC BY licenses are compatible with PLOS license: CC BY 4.0, CC BY 2.0 and CC BY 3.0, meanwhile such licenses as CC BY-ND 3.0 and others are not compatible due to additional restrictions. 

If you are unsure whether you can use a map or not, please do reach out and we will be able to help you. The following websites are good examples of where you can source open access or public domain maps: 

* U.S. Geological Survey (USGS) - All maps are in the public domain. (http://www.usgs.gov

* PlaniGlobe - All maps are published under a Creative Commons license so please cite “PlaniGlobe, http://www.planiglobe.com, CC BY 2.0” in the image credit after the caption. (http://www.planiglobe.com/?lang=enl) 

* Natural Earth - All maps are public domain. (http://www.naturalearthdata.com/about/terms-of-use/)

5. In the online submission form, you indicated that your data is available only on request from a third party. Please note that your Data Availability Statement is currently missing [the name of the third party contact or institution / contact details for the third party, such as an email address or a link to where data requests can be made]. Please update your statement with the missing information. 

6.We have amended your Competing Interest statement to comply with journal style. We kindly ask that you double check the statement and let us know if anything is incorrect. 

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 

- Abstract: I think that the conclusion is too strong. A ecological study cannot demonstrate an hypothesis. Consider using “suggest” or “support”.

- As temperature is a major confounder, I wonder how the model including only temperature has improved when the number of COVID diagnoses were added to the model. Could authors describe? Maybe using LR test.

- I suggest that the information in this paper could be relevant to the discussion and support the use of ecological methods.

- COVID toes were commonly associated with positive results in the family members, not the patient. doi: 10.1016/j.annder.2020.11.005. 

Reviewer #2:

I have one major concern that should be addressed:

- The authors conclude that they demonstrate a method that could support tracking of COVID-19 viral spread in the community. I strongly disagree with this finding. The study included a subset of 3,687 confirmed cases of COVID-19 at a time where the number of confirmed cases in the population under study was close to 40,000. I believe this study's findings are strongly biased by increased likelihood of patients presenting to a GP if they had COVID-19 and then also subsequently developed chilblains. The study is still publishable, but with the removal of the conclusion for the method having potential as a surrogate measure for the spread of COVID-19 infections. I suggest the conclusion should be more focused on increasing clinician awareness of the potential for chilblains in their COVID-19 patients - not anything to do with surveillance for COVID-19.

Other minor comments are:

- Lines 145-146 - sentence starting with We obtained ... does not make sense - use of BOM

- The increased RR for 0-16 year olds is likely associated with the increased likelihood of parents to take their children to the GP with the combined conditions. This should be made clear in the paper and references included to show that this is a known phenomenon.

- Please label Table 1 more appropriately, footnote any abbreviations, and include numbers in the Table.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLOS Glob Public Health. doi: 10.1371/journal.pgph.0000488.r003

Decision Letter 1

Kevin Escandón

26 Sep 2022

Snotwatch COVID-Toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia

PGPH-D-22-00669R1

Dear Miss Sawires,

We are pleased to inform you that your manuscript 'Snotwatch COVID-Toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia' has been provisionally accepted for publication in PLOS Global Public Health.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact globalpubhealth@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.

Best regards,

Kevin Escandón, MD, MSc

Academic Editor

PLOS Global Public Health

***********************************************************

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 File. Appendix A: Chilblains, COVID-19 disorder and suspected COVID-19 disorder lead and lag analysis results.

    Table A: COVID-19, suspected COVID-19 and temperature associations with chilblains with leads and lags.

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    PHNs have data sharing agreements including research with constituent general practices and provide them with a data analytics and reporting service in the areas of clinical, business, accreditation, and quality improvement. PHNs are the owner of the de-identified GP data collected from general practices and have provided permission to their contracted data custodian Outcome Health to supply a defined subset of this GP data to the project through the POpulation Level Analysis and Reporting (POLAR) platform, developed and deployed by Outcome Health. Research requests are processed through the Aurora Primary Care Research Institute. The subset of the de-identified GP data was sourced from 537 general practices and was used to contribute to advancing the evidence base by sharing de-identified, patient level data for ethics-reviewed, translational research. Data for this study can be made available through contacting Outcome Health via admin@outcomehealth.org.au.


    Articles from PLOS Global Public Health are provided here courtesy of PLOS

    RESOURCES