key: cord-0853996-r93ogrof
authors: Wen, Jingjing; Suo, Huinan; Zhang, Yamin; Tao, Juan
title: Risk of COVID-19 infection among lupus erythematosus patients and rheumatoid arthritis patients: a retrospective study in Hubei, China
date: 2021-02-12
journal: Eur J Dermatol
DOI: 10.1684/ejd.2020.3926
sha: 4722372866917fe77882bde1a7064e35315bef36
doc_id: 853996
cord_uid: r93ogrof

nan

Since both lupus erythematosus (LE) and rheumatoid arthritis (RA) patients need long-term treatment with immunosuppressive medications [1] , they may have an increased risk of viral infection, including SARS-CoV-2 [2, 3] . Hydroxychloroquine (HCQ), a conventional drug for LE or RA, could effectively inhibit SARS-CoV-2 in vitro, while its clinical efficacy remains unclear [4] . Although a randomized trial showed that HCQ cannot prevent symptomatic infection after SARS-CoV-2 exposure [5] , more studies are required to investigate the risk of SARS-CoV-2 infection among LE/RA patients with immunosuppressive medications. Furthermore, according to recommendations by the EULAR, the maintenance of immunomodulating and immunosuppressive therapies is suggested during the COVID-19 pandemic to avoid disease relapse. Limited data are available on the adherence to therapy in patients with LE or RA during the COVID-19 pandemic. Therefore, we explored the risk of COVID-19 infection in LE and RA patients, the possible effect of different treatments on the clinical manifestation of COVID-19, and adherence to therapy in Wuhan, China. We conducted a retrospective cohort study in Wuhan Union Hospital via electronic medical records and one-to-one telephone correspondence during follow-up from 22 nd March 2020 to 25 th March 2020. A total of 338 hospitalized patients diagnosed with LE/RA from 1 st January 2019 to 13 th March 2020 were included (supplementary table 1). Three patients were admitted with severe COVID-19. One patient had close contact with a confirmed COVID-19 case, whereas the other two did not according to their self-reports. Two systemic lupus erythematosus (SLE) patients treated with HCQ were in a critical condition with COVID-19, and one RA patient without HCQ had severe pneumonia (table 1 ). One patient with SLE, concurrent with nephritis, died of respiratory failure because of COVID-19. Although it was not possible to confirm an association between autoimmunity and COVID-19, the overall occurrence of COVID-19 in our study (3/338; 0.89%) appears to be higher than Wuhan's overall infection rate (0.46%; 50,340/10,000,000 based on city-wide testing; up to June 23 rd , 2020). The incidence of COVID-19 in LE/RA patients and critical condition of three COVID-19 patients might be attributed to several factors. Firstly, these patients received longterm immunosuppressive therapy. We wonder whether their immunocompromised status may have led to COVID-19. We compared the rate of COVID-19 infection between LE/RA patients with and without immunosuppressive medications (p>0.05). It suggested that immunosuppressive drugs do not increase the risk of COVID-19 infection, which is consistent with previous reports [6] . A larger sample size and multicentre studies are needed to draw a definitive conclusion regarding the effect of immunosuppression therapy against COVID-19. Secondly, all of the patients were resident in Wuhan or had potential COVID-19 exposure; their onset occurred during the early stage of the epidemic in Wuhan, suggesting that patients' awareness of protection may have been lacking at that time. In our study, 211 patients including two COVID-19 patients received HCQ at a dose below 5 mg/kg (medium duration of HCQ treatment: 11 months) (supplementary table 2). Due to the small sample size and retrospective method, we failed to establish a relationship between COVID-19 infection and LE or RA in patients treated with HCQ. Thirty-two RA/LE patients discontinued previous treatments and half of them suspended treatment due to city lockdown for COVID-19. Compared with patients who adhered to medication therapy, discontinuing medication positively correlated with worse LE or RA clinical out- Comparison between discontinued due to COVID-19 and continued. comes (clinical outcome score: 2.86 ± 1.12 vs 1.82 ± 0.96; p < 0.001) (table 2). Commonly, interruption of slowacting disease-modifying antirheumatic drugs, after one to two weeks, is less concerning due to relatively long halflives [7] . In the COVID-19 group, treatment was interrupted after four weeks to several months. Therefore, we speculated that long-term interruption of immunosuppressive therapy would worsen their clinical outcomes. These findings call for vigilance by healthcare providers regarding patient adherence to previous therapy during the COVID-19 pandemic. Our study reveals that RA/ LE patients developed severe COVID-19, and immunosuppressive medications could be continued during the COVID-19 pandemic. Hence, medical institutions need to enhance their awareness of selfprotection through public campaigns and routine patient education, providing online medical consultation and medication via postal services to make sure patients receive timely treatment. Multicentre trials with a larger sample size and case-control studies are needed to confirm the relationship between COVID-19 and RA/LE. 

Dystrophic epidermolysis bullosa (DEB) is one of the four major types of inherited epidermolysis bullosa, the prototypic skin fragility disorder [1] . DEB is characterized by blister formation below the lamina densa of the cutaneous basement membrane zone (BMZ) and by mutations in the COL7A1 gene, encoding type VII collagen (colVII). DEB is inherited as a dominant or recessive trait and several subtypes are distinguished based on clinical features. A peculiar subtype, self-improving DEB (previously referred to as "bullous dermolysis of the newborn"; OMIM #131705), is characterized by major improvement or com- plete resolution of skin fragility within the second year of life [1] . Self-improving DEB blisters are predominantly acral and heal with no or minimal scarring. Laboratory diagnostic features are granular colVII deposits within the epidermis, and specific cytoplasmic inclusions (stellate bodies) in keratinocytes [2, 3] . Self-improving DEB can be dominantly or recessively inherited [1] . We describe the clinical, immunopathological and ultrastructural features of a case of self-improving dominant DEB (SI-DDEB) due to the glycine substitution p.Gly2037Glu in colVII and discuss the phenotypic variability associated with this mutation. A full-term female infant, the third child of healthy non-consanguineous Chinese parents, developed tense blisters on the extremities from the fifth day of life ( figure 1A) . The oral mucosa was also affected and subungual haemorrhages were present. Lesions healed with milia and minimal atrophic scarring. Muco-cutaneous fragility rapidly improved in the first months of life. Following informed consent, a skin biopsy and blood sample were taken at three months of age. Immunofluorescence mapping (IFM) showed colVII-positive granular deposits within the epidermis, and linear labelling at the BMZ ( figure 1C) . Ultrastructural examination demonstrated cleavage below the lamina densa and a few rudimentary anchoring fibrils. Rough endoplasmic reticulum (RER)-bound perinuclear inclusions were present mainly within suprabasal keratinocytes ( figure 1D ). These were partially filled with granular content and some elongated electron-dense structures, compatible with stellate bodies ( figure 1D) . Molecular testing performed in the patient and healthy parents revealed a de novo heterozy-

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