key: cord-1022730-t5a4ic62 authors: Fu, Xue-Lei; Qian, Yan; Jin, Xiao-Hong; Yu, Hai-Rong; Du, Lin; Wu, Hua; Chen, Hong-Lin; Shi, Ya-Qin title: COVID-19 in patients with systemic lupus erythematosus: A systematic review date: 2022-04-05 journal: Lupus DOI: 10.1177/09612033221093502 sha: cb1d5286ea5356724c4bb851d0130c509e29749a doc_id: 1022730 cord_uid: t5a4ic62 The objectives of the study were to review the articles to identify (a) the epidemiology of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19); (b) the clinical characteristics of SLE patients with COVID-19; (c) the treatment of COVID-19 in SLE patients; and (d) the impact of COVID-19 pandemic on SLE patients. PubMed was systematically reviewed for literature published from December 2019 to June 2021. Our search was limited to human studies, with language restriction of English. Studies were included if they reported COVID-19 in SLE patients. Our systematic review included 52 studies. The prevalence of COVID-19 infection ranged from 0.0% to 18.1% in SLE patients, and the hospitalisation rates ranged from 0.24% to 10.6%. COVID-19 infection is likely to mimic SLE flare. Hydroxychloroquine (HCQ) was ineffective in prevention of COVID-19, and SLE patients with COVID-19 faced difficulty in healthcare access, had financial constraints and suffered from psychological distress during the pandemic. The pandemic had a significant effect on mental and physical health. Adequate healthcare access, along with containment policies, social distancing measures and psychological nursing was required. The coronavirus disease 2019 (COVID-19) pandemic leads to serious illness in a considerable proportion of infected patients. 1, 2 As of 27 July 2021, the pandemic of COVID-19 has been responsible for more than 194 million infections and four million deaths globally. 3 Some populations are at greater risk from poor outcomes related to this disease, including the elderly, male, obese people and individuals with any comorbidities, especially those with hypertension, cardiovascular disease or diabetes. 4 Prognoses of COVID-19 vary widely between individuals. Systemic lupus erythematosus (SLE) patients are prone to COVID-19 infection on account of the aberrant immune responses inherent to the disease and the frequent treatment of immune-suppressants. 5 Age over 60 years, male sex, Black and Asian ground, steroids, cyclophosphamide or rituximab and high disease activity were related to increased risk of poor consequences of COVID-19 in SLE patients. 6 The purposes of the systematic review were to evaluate the epidemiology of SLE and COVID-19, to identify the clinical characteristics of SLE patients with COVID-19, to clarify the treatment of COVID-19 in SLE patients and to assess the impact of COVID-19 pandemic on SLE patients. The review followed the Preferred reporting items for systematic reviews guidelines (PRISMA) 7 for articles that revealed the relationship between COVID- 19 Studies were eligible if they reported relationship between COVID-19 and SLE. Observational studies (e.g. case reports and series, cross-sectional studies, case-control studies and cohort studies), correspondence with relevant clinical data and randomised controlled trials were included. Comments, animal studies and in vitro studies were excluded. Studies were ineligible if the full texts were not available. Two independent reviewers conducted the phases of screening, eligibility and inclusion. They reviewed titles and abstracts for potential inclusion. Both reviewers inspected the full text for potential studies. Any discrepancy was resolved through consensus amongst review authors or through adjudication by an additional review author. Two authors tabulated outcome results from the included studies in detail, to examine and evaluate the potential patterns within the data. Quality assessment was performed using criteria adapted from the National Institutes of Health. 8 A narrative synthesis was performed within the following categories: (a) the epidemiology of SLE and COVID-19; (b) the clinical characteristics of SLE patients with COVID-19; (c) the treatment of COVID-19 in SLE patients; and (d) the impact of COVID-19 pandemic on SLE patients. We initially yielded 253 literature, of which 52 met the eligibility criteria ( Figure 1 ). The quality assessment of the 52 articles revealed a high quality in 19/52 (36.5%) studies. Characteristics and outcomes are shown in Table 1 . Thirteen studies reported the epidemiology of SLE and COVID-19. The proportion of SLE patients varied from 7% to 32.9% in rheumatic patients infected with COVID-19. 25, 36, 42 Relative to patients with other autoimmune diseases, SLE patients with COVID-19 infection appeared to develop more severe manifestations of COVID-19 infection, with higher rates of hospitalisation, invasive ventilation requirement or death. 21, 25, 36, 39, 53 The prevalence of COVID-19 infection varied between 0.0% and 18.1% in SLE patients, 13, 18, 19, 41, 45, 59 and the hospitalisation rates ranged from 0.24% to 10.6%. 19, 45, 59 A decline in SLE hospitalisation rate was found during the COVID-19 pandemic, and disease flare (38.9%) and infection (22.2%) were considered as the main reasons for hospitalisation in SLE patients. 15 The clinical characteristics of SLE patients with COVID-19 The clinical characteristics of SLE patients with COVID-19 were reported in 23 studies. COVID-19 infection might mimic SLE flare, and sometimes could occur concurrently with SLE flare. 14, 17, 29, 30, 40, 46, 51 The main clinical symptoms of COVID-19 infection in SLE patients were fever, cough, shortness of breath, headache, increased respiratory rate, myalgia, rhinorrhoea and diarrhoea. 13, 37, 45, 46 The clinical presentation described in paediatric SLE population with COVID-19 might be similar to those in adults, characterised by increased work of breathing and low oxygen saturation. 49 Bozzalla Cassione et al. 13 also reported that 11 of 12 SLE patients with COVID-19 are likely to have a mild and selfresolving disease course. However, patients with mutivisceral SLE damage would be at risk of severe COVID-19. 52,55 A patient of SLE with COVID-19 could develop COVID-19related varicelliform rashes, leptomeningeal involvements, thrombotic events and immune thrombocytopenia. 9, 20, 28, 33, 35, 48 The infection of COVID-19 could trigger the presentation or exacerbation of SLE. 12, 27, 44, 57 The treatment of COVID-19 in SLE patients Thirteen studies reported the treatment of COVID-19 in SLE patients. Previous use of immunosuppressants did not seem to influence COVID-19 infection or symptoms in SLE patients. 22, 23 Intravenous immunoglobulin treatments and increased dose of corticosteroids might be effective for patients with COVID-19 and SLE. 23, 40 According to the available evidence, hydroxychloroquine (HCQ) did not appear to prevent the occurrence of COVID-19. 10, 23, 31, 32, 37, 40, 45, 47, 51, 60 Cardiovascular adverse events were frequently reported in patients with SLE under HCQ or chloroquine (CQ) treatment, 26 and paediatric SLE patients might develop hyperpigmentation induced by HCQ. 34 The impact of COVID-19 pandemic on SLE patients Fifteen studies reported the impact of COVID-19 pandemic on SLE patients. During this lockdown period, SLE patients experienced supply shortages, missed the doses of drugs, underwent financial constraints and spent more money on healthcare. 38, 45, 46 Many patients faced problems of reduced care access, such as missing their scheduled follow-up visits and being unable to get their investigations. 14,24,46 A few patients discontinued previous treatments, which might result in worse SLE clinical outcomes. 11, 45, 55, 58, 59 Besides possible clinical effects, treatment discontinuation might cause psychological consequences including anxiety, concern and probably a sense of uncertainty about the future. 16, 24, 43, 56 Patients also displayed a high adherence to social distancing measures, 18,56,58 but it often came at the cost of physical activity, increased pain, disease activity, anxiety, depression and sleep disorders. 11, 50, 54, 56 Discussion This systematic review found that there was variation in infection rates and hospitalisation rates in SLE patients across the included studies. HCQ lacked preventive effect on COVID-19, and SLE patients with COVID-19 experienced supply shortages, missed the doses of drugs, underwent financial constraints and suffered from psychological distress during the pandemic. The COVID-19 infection rates in SLE patients ranged from 0.0% to 18.1%. This wide variation might be attributed to prevention of contagion adopted by SLE patients. The strict implements of the precaution in public could greatly contain the outbreak. 61 Social distancing measures along with handwashing and mask-wearing could play important roles in tackling COVID-19 62 . SLE patients were found to have higher overall attack rates of COVID-19 relative to the general population. 45, 55 This is possibly because of immune dysfunction, use of immunosuppressant agents, impairment from prior disease activity, presence of comorbidities and overexpression of angiotensin-converting enzyme two receptor. 6 Disease flare was the main cause of hospitalisation in SLE patients. 15 Treatment discontinuation was likely to result in SLE flare. 59, 63 The reasons for poor adherence in medications included concern about adverse effects, being distracted, life getting in the way, uncertainty or disagreement about the important role of medications and having personal reasons. 64 Furthermore, HCQ shortage was frequently reported by SLE patients in our study. HCQ discontinuation or long-term dose reduction was always linked to increased risk of flare in SLE patients. [65] [66] [67] Therefore, abrupt medication withdrawal must be assessed with caution based on infection risk and comorbidities of SLE patients. 59 In our study, HCQ was not effective in COVID-19 prevention in SLE patients. Similarly, data from completed studies and randomised controlled trials suggest that HCQ does not work. 68 Previous meta-analysis has proved that although HCQ treatment is safe, it could not decrease mortality or promote clinical/virological recovery in COVID-19 patients. 69 Whereas the evidence supporting the HCQ treatment for COVID-19 is not clear, HCQ has shown great efficacy against immune-mediated diseases. Therefore, physicians and individuals should avoid misuse of HCQ for the prophylaxis of COVID-19. 70 SLE is related to high health-care costs and great loss of productivity. 71 Patients with SLE have an average excess expenditure of more than $30 per month on healthcare during the outbreak. Mental health problem was a concurrent epidemic of the pandemic. 72 Mental problems were frequently reported during this period. 73 While anxiety, depression and economic stressors are common phenomena around the world, specific behavioural responses are heavily influenced by government stances, misinformation, conspiratorialism and competing demands of resource scarcity. 74 Our systematic review has several limitations. First, assumptions on the COVID-19 in SLE patients were mostly based on small sample sizes and thus should be treated with reserve. Second, studies not published in English and not reporting clinical information were excluded, so some studies on the subject may not have been identified. In conclusion, SLE patients experience a great physical toll and emotional distress during the COVID-19 pandemic. Adequate medical services, containment policies and social distancing measures were essential to limit the effect of COVID-19 on SLE patients. Psychological approaches were also required during this period. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Hong-Lin Chen  https://orcid.org/0000-0003-0147-6863 A pneumonia outbreak associated with a new coronavirus of probable bat origin Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review World Health Organization. Situation reports. Weekly epidemiological update on COVID-19 -27 The clinical characteristics and risk factors of severe COVID-19 COVID-19 and systemic lupus erythematosus: focus on immune response and therapeutics Clinical management of Lupus patients during the COVID-19 pandemic Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement Venous thrombosis in a systemic lupus erythematosus patient with antiphospholipid antibodies coinciding with mild Covid-19 COVID-19 in a patient with a flare of systemic lupus erythematosus: A rare casereport Isolation, behavioral changes and low seroprevalence of SARS-CoV-2 antibodies in patients with Systemic Lupus Erythematosus or Rheumatoid arthritis The first case of systemic lupus erythematosus (SLE) triggered by COVID-19 infection COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine COVID-19 infection in patients with systemic lupus erythematosus: Data from the Asia Pacific Lupus Collaboration Impact of COVID-19 pandemic on hospitalisation of patients with systemic lupus erythematosus (SLE): report from a tertiary hospital during the peak of the pandemic Hydroxychloroquine availability during COVID-19 crisis and its effect on patient anxiety COVID-19 Presenting as Lupus Erythematosus-Like Syndrome Are patients with systemic lupus erythematosus at increased risk for COVID-19? Leveraging the United states epicenter to provide insights on COVID-19 in patients with systemic lupus erythematosus COVID-19 coagulopathy in a patient with systemic lupus erythematosus and antiphospholipid antibodies Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases COVID-19 and systemic lupus erythematosus: a case series Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments Concerns, healthcare use, and treatment interruptions in patients with common autoimmune rheumatic diseases during the COVID-19 pandemic Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports Can the SARS-CoV-2 infection trigger systemic lupus erythematosus? A case-based review Leptomeningeal involvement in a patient with systemic lupus erythematosus infected by COVID-19 COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Successful recovery of recurrence of positive SARS-CoV-2 RNA in COVID-19 patient with systemic lupus erythematosus: a case report and review Monitoring of patients with systemic lupus erythematosus during the COVID-19 outbreak Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study Exacerbation of immune thrombocytopaenia triggered by COVID-19 in patients with systemic lupus erythematosus Hydroxychloroquineinduced hyperpigmentation in a 14-year-old female with systemic lupus erythematosus Concomitant new diagnosis of systemic lupus erythematosus and COVID-19 with possible antiphospholipid syndrome. Just a coincidence? A case report and review of intertwining pathophysiology High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19: first results of ReumaCoV Brasil registry Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine Hydroxychloroquine shortages among patients with systemic lupus erythematosus during the COVID-19 pandemic: experience of the systemic lupus international collaborating clinics Coronavirus disease 2019 (COVID-19) in autoimmune and inflammatory conditions: clinical characteristics of poor outcomes A case of SLE with COVID-19 and multiple infections Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study Concerns and needs of patients with systemic lupus erythematosus regarding hydroxychloroquine supplies during the COVID-19 pandemic: results from a patient-centred survey a case of systemic lupus erythematosus flare triggered by severe coronavirus disease 2019 COVID-19 in systemic lupus erythematosus: Data from a survey on 417 patients Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort Effect of preexposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the Open-SAFELY platform Systemic lupus erythematosus and varicella-like rash following COVID-19 in a previously healthy patient Acute respiratory distress syndrome and COVID-19 in a child with systemic lupus erythematosus Psychological state and associated factors during the 2019 coronavirus disease (COVID-19) pandemic among filipinos with rheumatoid arthritis or systemic lupus erythematosus COVID-19 among Malaysian patients with systemic lupus erythematosus on hydroxychloroquine Case series of chronic inflammatory rheumatic disease patients infected by coronavirus disease 2019 (COVID-19) Patients with lupus with COVID-19: University of Michigan experience Evaluation of mental health factors among people with systemic lupus erythematosus during the SARS-CoV-2 pandemic Risk of COVID-19 infection among lupus erythematosus patients and rheumatoid arthritis patients: a retrospective study in Hubei, China Factors related to knowledge, perception, and practices towards COVID-19 among patients with autoimmune diseases: a multicenter online survey Systemic lupus erythematosus manifestation following COVID-19: a case report SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients Impact of first wave of SARS-CoV-2 infection in patients with Systemic Lupus Erythematosus: Weighting the risk of infection and flare SARS-CoV-2 infection and COVID-19 in 5 patients in ecuador after prior treatment with hydroxychloroquine for systemic lupus erythematosus Why does the spread of COVID-19 vary greatly in different countries? Revealing the efficacy of face masks in epidemic prevention Impact of self-imposed prevention measures and short-term government-imposed social distancing on mitigating and delaying a COVID-19 epidemic: A modelling study Risk factors for the flare of systemic lupus erythematosus and its influence on prognosis: a single-center retrospective analysis Barriers to medication adherence and degree of nonadherence in a systemic lupus erythematosus (SLE) outpatient population Possible consequences of a shortage of hydroxychloroquine for patients with systemic lupus erythematosus amid the COVID-19 pandemic A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus Outcomes of systemic lupus Erythematosus in patients who discontinue hydroxychloroquine Prophylaxis for COVID-19: a systematic review Hydroxychloroquine in the treatment of coronavirus disease 2019: Rapid updated systematic review and meta-analysis Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know The socioeconomic burden of SLE Investigating the effect of national government physical distancing measures on depression and anxiety during the COVID-19 pandemic through meta-analysis and meta-regression Public mental health problems during COVID-19 pandemic: a large-scale meta-analysis of the evidence Overview of behavioural and psychological consequences of COVID 19. Curr Opin Psychiatry 2021