key: cord-0701669-ur8jyua5 authors: García‐Gil, Miguel Fernando; Monte‐Serrano, Juan; Lapeña‐Casado, Alejandro; Villagrasa‐Boli, Pablo; Ramírez‐Lluch, Mar; Martínez‐Pallás, Isabel; Bularca, Aura; Aldea‐Manrique, Beatriz; Benito‐Ruesca, Rafael; Ventura‐Faci, María Purificación; Ara‐Martín, Mariano title: No antibody response in cutaneous manifestations associated with COVID‐19: An observational study of 64 cases with microbiological and clinical characterization date: 2021-10-08 journal: Dermatol Ther DOI: 10.1111/dth.15142 sha: ee6d61822e75f042a475482806ede169a57e9840 doc_id: 701669 cord_uid: ur8jyua5 Background: The microbiological diagnosis of skin lesions related to COVID‐19 is not well known. Objective: Perform a microbiological diagnosis in COVID19‐related cutaneous manifestations. Methods: A cross‐sectional study was performed with 64 patients with cutaneous manifestations associated with COVID‐19 who underwent serological and nasopharyngeal reverse transcription polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2. Results: Out of the 64 patients, 6 patients had positive RT‐PCR, with all of them developing SARS‐CoV‐2 IgG and 4 of them had positive IgM + IgA. Of the 58 patients with negative RT‐PCR, 8 cases had positive IgM + IgA and only one of them had IgG seroconversion. Therefore, the infection was demonstrated in 7 cases (10.9%) and was doubtful in 7 other cases (10.9%) who presented negative RT‐PCR and presence of IgA + IgM without subsequent seroconversion of IgG. Fifty patients (78.1%) had negative serological tests. The most frequent cutaneous pattern was pseudo‐chilblain (48.4%) followed by maculo‐papular pattern (26.6%), urticarial lesions (10.9%), vesicular eruptions (6.3%) and livedoid pattern (4.7%). The maculo‐papular pattern showed the highest positivity in RT‐PCR (3 cases; 17.6%) and serologies (4 cases; 23.5%). Skin lesions developed after the systemic symptoms in most patients (19 cases; 61.3%). Conclusions: Microbiological confirmation tests may not be an effective diagnostic technique for COVID‐related cutaneous manifestations or that attributed lesions are not related to COVID‐19. Confounding factors such as adverse drug reaction, serological cross‐reactions with other viruses, the low production of antibodies in asymptomatic or mild forms of COVID‐19 or its rapid disappearance, increase diagnostic uncertainty. Several skin manifestations have been associated with COVID-19, however, the microbiological profile of the patients presenting them has not been sufficiently studied. We performed a cross-sectional, single-center study in a Spanish tertiary hospital. The study was conducted between April 22 and June 3, 2020. The objective of the study was to determine the prevalence of confirmation markers of coronavirus infection in a cohort of patients with cutaneous manifestations suspected of COVID-19, performing nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) and serological tests for SARS-CoV-2. We recruited suspicious cases of COVID-19, that met the following criteria: skin lesions belonging to the groups described as related to COVID-19 (pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, livedo or necrosis and others) 1-4 that were associated with: symptoms compatible with COVID-19 (fever, cough, dyspnea, headache, anosmia, ageusia, myalgia, nausea, vomiting or diarrhea) contact with confirmed or suspected cases of COVID-19. Patients without systemic symptoms and without contact with COVID-19 patients who presented a pseudo-chilblain pattern not associated with exposure to cold, personal history of chilblain lesions or other causes were also included. Demographics (sex, age) and clinical data (smoking, previous dermatological diseases, duration of suspected skin disorder, systemic symptoms and treatment employed) were collected. In the 7 days following the consultation, the microbiological tests were performed at the same day: nasopharyngeal swab for the detection of SARS-CoV-2 RNA by RT-PCR (Abbott Real Time SARS-CoV-2 assay, Abbott Park, Illinois; Sensitivity:100 copies/ml; Specificity: 100%), serological tests on blood for SARS-CoV-2 IgM + IgA antibodies (COVID-19 VIRCLIA ® IgM + IgA, Vircell, Spain; At 9 days of the infection: Sensitivity:89%; Specificity:100%) and antibodies IgG Sixty-seven patients with suspicious cutaneous lesions were recruited. Three patients refused to undergo any complementary tests. Therefore, 64 patients were included in our study. Twenty-seven patients (42.2%) were male and 37 (57.8%) were female. Their mean age was 28.09 years old (SD: ±20). The percentage of patients under the age of 6 years old was 7.8%; 43.8% were between 6 and 18 years old, 28.1% were between 18 and 50 years old, and 20.3% were older than 50 years old (Table S1 ). The most frequent cutaneous manifestation was pseudo-chilblain (Table 1 and Tables S2 and S3) . In our database, the most frequent pattern was the pseudo-chilblain pattern followed by the maculopapular pattern and in the early ages of life, we observed that the pseudo-chilblain pattern is especially frequent as has been observed in other studies. 4, 5 According to our methodological criteria, seven patients ( It must also be taken into account that the majority of patients in the study are young (7.8% under 6 years old, 43.8% between 6 and 18 years old). This young population has frequently negative serologic results for SARS-CoV-2. 12 These data must be validated with more prospective studies that obtain long-term data because late and low antibody production that occurs in patients with mild or moderate forms of COVID-19, as in our series. 13 In addition, SARS-CoV-2 induces memory T cell responses in antibody-seronegative and antibody-seropositive individuals with asymptomatic or mild COVID-19, so that the fight against this virus could be more related to this mechanism than to the production of antibodies. 14, 15 In conclusion, the low seroprevalence of SARS-CoV-2 anti- The authors declare no conflict of interest. Duration of skin lesions at the time of the serologies were performed. Ten patients did not remember the duration of the skin lesions. + À + À + À + À + À of the data analysis. García-Gil, Monte-Serrano, Lapeña-Casado and Ara-Martín contributed equally. The data that supports the findings of this study are available in the supplementary material of this article. 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