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1.
J Paediatr Child Health ; 58(4): 719-720, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1807193
2.
Vasc Med ; 26(5): 576-578, 2021 10.
Article in English | MEDLINE | ID: covidwho-1736193
3.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Article in English | MEDLINE | ID: covidwho-1713295

ABSTRACT

An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARS-CoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as "covid toes" during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.


Subject(s)
COVID-19/complications , Chilblains/immunology , Adult , COVID-19/epidemiology , Chilblains/epidemiology , Chilblains/virology , Connecticut/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Young Adult
7.
Pediatr Dermatol ; 39(1): 77-83, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1607511

ABSTRACT

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an increasing number of chilblain-like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS-CoV-2 infection has not been unequivocally established. METHODS: In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. RESULTS: The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients - 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT-PCR for SARS-CoV-2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS-CoV-2 RNA in skin biopsies, both with real-time polymerase chain reaction (RT-PCR) and RNAscope in situ hybridization (ISH). LIMITATIONS: Limited number of cases, unavailability of laboratory confirmation of COVID-19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. CONCLUSIONS: These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral endothelial damage followed by an IFN-I or complement-mediated inflammatory phase. Further observations on a large number of patients are needed to confirm this hypothesis.


Subject(s)
COVID-19 , Chilblains , Epstein-Barr Virus Infections , Adolescent , Chilblains/diagnosis , Child , Female , Herpesvirus 4, Human , Humans , In Situ Hybridization , Laboratories , RNA, Viral , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
8.
Dermatol Ther ; 35(3): e15298, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1606649

ABSTRACT

COVID toes or chilblain-like skin lesions represent a widespread and specific skin presentation mostly in the feet that may be attributed to COVID-19 infection. They may last for several months. We conducted this study to investigate chilblain-like lesions in children during the COVID-19 pandemic, any predisposition, location, clinical course, and prognosis. We searched Google Scholar, Scopus, and Medline (PubMed) databases using the following keywords: "Coronavirus" OR "COVID-19" AND "Chilblains" OR "Pernio" OR "Perniosis" OR "Children" OR "Cutaneous" OR "skin." The inclusion criteria were: (a) Studies that described the specific vascular skin lesion. (b) Studies that included patients aged >1 month till 18 years. (c) Case reports, case series, retrospective or prospective cohort studies, case-control studies. A total of 28 articles were included. The total number of children with chiblain-like lesions (CLL) was 433. The mean age of children presenting CLL during the COVID-19 pandemic was estimated as 12.58 ± 2.15. Of note, 53.6% of them were male. The nasopharyngeal SARS-CoV-2 RT-PCR test and anti-SARS-CoV-2 antibodies were mostly negative for the virus. In conclusion, it is crucial to be familiar with various presentations of COVID-19 infection and their clinical significance to approach the earliest diagnosis, immediate treatment, estimate the prognosis, and finally isolate the patients to prevent spreading. Chilblain-like lesions as a possible cutaneous presentation of COVID-19 in children may last several months with the indolent course.


Subject(s)
COVID-19 , Chilblains , COVID-19/diagnosis , COVID-19/epidemiology , Chilblains/diagnosis , Chilblains/epidemiology , Chilblains/etiology , Child , Humans , Infant , Male , Pandemics , Prospective Studies , Retrospective Studies , SARS-CoV-2
9.
J Eur Acad Dermatol Venereol ; 36(1): 24-38, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1570788

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.


Subject(s)
COVID-19 , Chilblains , Diagnostic Tests, Routine , Humans , Pandemics , SARS-CoV-2
10.
J Dtsch Dermatol Ges ; 19(10): 1521-1523, 2021 10.
Article in English | MEDLINE | ID: covidwho-1511300
12.
Clin Dermatol ; 39(3): 380-383, 2021.
Article in English | MEDLINE | ID: covidwho-1491858

ABSTRACT

More than 40 million people have been infected with the severe acute respiratory syndrome coronavirus 2 since the first infection was reported in December 2019 from Wuhan, China. Multiple reports of cutaneous manifestations of the virus have been described, including a pernio-like eruption, recently termed "COVID toes." We have reviewed the published case series on "COVID toes" in addition to studies identifying possible pathogenic mechanisms behind the eruption.


Subject(s)
COVID-19 , Chilblains , Exanthema , Chilblains/diagnosis , Chilblains/epidemiology , Humans , SARS-CoV-2 , Toes
13.
Clin Dermatol ; 39(3): 374-379, 2021.
Article in English | MEDLINE | ID: covidwho-1491854

ABSTRACT

The novel coronavirus SARS-CoV-2 has caused coronavirus disease-2019, known as COVID-19, now a pandemic stressing millions of individuals worldwide. COVID-19 is a systemic respiratory infection that may have dermatologic signs and systemic sequelae, a devastating public health challenge with parallels to the two great influenza pandemics of the last century. Skin lesions linked with COVID-19 have been grouped into six categories, with three distinct indicative patterns: vesicular (varicella-like), vasculopathic, and chilblains-like (including "COVID toes" and "COVID fingers") plus the following three less suggestive patterns: dermatitic, maculopapular, and urticarial morphologies. Vasculopathic changes are the most concerning, in some patients, reflecting a devastating blood clotting dysfunction. We discuss the ways to detect, prevent, and treat COVID-19, keeping in mind the context of possible cutaneous markers of COVID-19 to enhance detection.


Subject(s)
COVID-19 , Chilblains , Humans , Public Health , SARS-CoV-2 , Skin
14.
Eur J Clin Microbiol Infect Dis ; 40(10): 2243-2248, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1491170

ABSTRACT

In a large regional observational cohort study of adult (≥ 18 years), outpatients with COVID-19, prevalence, characteristics, and outcome of patients with rash and/or chilblain-like lesions (CLL), compared with population without cutaneous features, were studied. In total, 28,957 outpatients were included; the prevalence of rash and CCL were 9.5% and 3.7%, respectively. Presence of rash was significantly associated with presence of asthenia, shivers or myalgia, respiratory and gastro-intestinal symptoms, and anosmia/ageusia. The presence of CCL was associated with chest pain, chest oppression, nausea/vomiting, and anosmia/ageusia. Patients with CCL were significantly less prone to an unfavourable outcome (hospitalization or death).


Subject(s)
COVID-19/complications , Chilblains/etiology , Exanthema/etiology , Adult , Aged , Chilblains/diagnosis , Cohort Studies , Exanthema/diagnosis , Female , Humans , Male , Middle Aged , Outpatients , Prognosis , SARS-CoV-2/genetics , SARS-CoV-2/physiology
15.
Br J Dermatol ; 185(6): 1176-1185, 2021 12.
Article in English | MEDLINE | ID: covidwho-1455515

ABSTRACT

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.


Subject(s)
COVID-19 , Chilblains , Interferon Type I , COVID-19/immunology , Chilblains/virology , France , Humans , Interferon Type I/immunology , Pandemics
16.
J Eur Acad Dermatol Venereol ; 36(2): e84-e85, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1450559
17.
Clin Microbiol Infect ; 28(2): 285-291, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1446539

ABSTRACT

OBJECTIVES: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2. METHODS: In this multicentre case-control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test. RESULTS: After adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis. DISCUSSION: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2.


Subject(s)
COVID-19 , Chilblains , Case-Control Studies , Chilblains/epidemiology , Communicable Disease Control , Humans , Pandemics , SARS-CoV-2
18.
J Invest Dermatol ; 141(12): 2791-2796, 2021 12.
Article in English | MEDLINE | ID: covidwho-1437509

ABSTRACT

Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.


Subject(s)
COVID-19/immunology , Chilblains/immunology , SARS-CoV-2/physiology , Animals , COVID-19/complications , Chilblains/complications , Humans , Immunity, Innate , Interferon Type I/metabolism
19.
J Eur Acad Dermatol Venereol ; 36(1): 24-38, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1429879

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.


Subject(s)
COVID-19 , Chilblains , Diagnostic Tests, Routine , Humans , Pandemics , SARS-CoV-2
20.
Acta Derm Venereol ; 101(12): adv00614, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1405390

ABSTRACT

Numerous cases of chilblains have been observed in the course if the COVID-19 pandemic. The aims of this study were to provide comprehensive follow-up data for patients reporting chilblains, and to determine the risk factors for incomplete recovery. Patients referred to 5 hospitals in France between March and May 2020 for chilblains were surveyed on December 2020. A teleconsultation was offered. Among 82 patients reporting chilblains, 27 (33%) reported complete recovery, 33 (40%) had recurrences of chilblains after their hands and feet had returned to normal, and 22 (27%) developed persistent acral manifestations, mostly acrocyanosis, with or without further recurrences of chilblains. Most recurrences of chilblains occurred during the following autumn and winter. A past history of chilblains was not associated with recurrences or persistent acral manifestations. Women had a significantly higher risk of developing recurrences or persistent acral manifestations (odds ratio 1.30; 95% confidence interval 1.06-1.59). In conclusion, two-thirds of patients reporting chilblains at the start of the COVID-19 pandemic experienced persistent or recurrent acral manifestations after a 10-month follow-up.


Subject(s)
COVID-19 , Chilblains , Biopsy , Chilblains/diagnosis , Chilblains/epidemiology , Female , Humans , Pandemics , SARS-CoV-2
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