key: cord-303192-il3s8lgp authors: Tam, Lai‐Shan; Tanaka, Yoshiya; Handa, Rohini; Chang, Chi‐Chen; Cheng, Yew Kuang; Isalm, Nazrul; Li, Mengtao; Lorenzo, Jose Paulo; Song, Yeong‐Wook; Yamamoto, Kazuhiko; Zeng, Xiaofeng; Haq, Syed Atiqul title: Care for patients with rheumatic diseases during COVID‐19 pandemic: A position statement from APLAR date: 2020-05-27 journal: Int J Rheum Dis DOI: 10.1111/1756-185x.13863 sha: doc_id: 303192 cord_uid: il3s8lgp nan The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China in December 2019. This disease now affects the whole world. Patients with rheumatic diseases are at higher risk of respiratory infections including influenza and pneumococcal pneumonia, which is attributed to the underlying disease, comorbidities and immunosuppressive therapy, 1 but to date we lack good information about the virus SARS-CoV-2. Nonetheless, immunosuppressive treatments are essential to control disease activity and prevent functional deterioration in these patients. Rheumatologists need to be vigilant in preventing rheumatic disease patients from contracting the disease during this pandemic, especially patients with chronic lung problems (eg scleroderma with lung fibrosis) and chronic kidney disease (eg lupus nephritis) and those on high-dose glucocorticoids and immunosuppressants (Appendix 1). In the desperate search to find effective treatments for COVID-19, drugs largely used by rheumatologists have entered the spotlight, including the caution against use of non-steroidal anti-inflammatory drugs (NSAIDs), the potential of antimalarials and biologic disease-modifying anti-rheumatic drugs (bDMARDs), for example anti-interleukin-6 (IL-6) and targeted synthetic DMARDS (tsDMARDs) Janus-activated kinase (JAK) inhibitors to manage cytokine storm syndrome (CSS)/cytokine release syndrome associated with COVID-19. Here, we try to provide guidance regarding clinical decision-making both for patients with COVID-19 and those with rheumatic diseases, and strategies to mitigate further harm to these patients. An Asia-Pacific League Against Rheumatism (APLAR) COVID-19 task force comprising rheumatologists from 9 Asia-Pacific countries was convened on 31 March, 2020. A set of guidance statements was developed and refined based on best available evidence up to 26 April, 2020 and expert opinion. Given the overall limited nature of the data, a systematic review was not performed. The final guidance statements integrate both the task force members' assessment of the evidence quality and the ratio of risk and benefit from the treatment or action. We assert that the key guiding principle should be to "first do no harm," especially given the unknown efficacy of proposed DMARDs and biologics and their established potential harms. This guidance document has been reviewed and endorsed by the APLAR executive committee and the APLAR scientific committee chairpersons. In the absence of a vaccine or a therapeutic agent, a "mitigation approach", including "social distancing", frequent hand washing and quarantining strategies are the primary interventions to hamper the spread of infection. Smoking can cause an increase in the release of IL-6 in bronchial epithelial cells, 4 and upregulate angiotensin-converting enzyme-2 (ACE2) receptors, the known receptor for SARS-CoV. 5 This is particularly relevant as some of the Asia-Pacific countries, for example China, has a high male smoking rate. 6 Globally the quality of evaluation, monitoring and treatment of comorbidities in rheumatic disease patients is variable with considerable scope for improvement. 7 Rheumatologists should be vigilant in assessing and managing comorbidities not only to improve morbidity and mortality, but hopefully to minimize risk of COVID-19 in rheumatic disease patients. In patients with acute respiratory tract infections, short-term use of NSAIDs are associated with increased risk of cardiovascular events and nephrotoxicity, [8] [9] [10] higher rates of complications, and delays in the prescription of effective antibiotic treatment. 11 Despite the lack of evidence relating specifically to people with COVID-19, regular NSAID use should not be recommended as the first line option for managing the symptoms of COVID-19. 12 Nonetheless, arthritis patients taking NSAIDs for symptomatic relief should continue their treatment as needed. Epidemiologic studies have identified advanced age, male gender and presence of comorbidities (hypertension, obesity, diabetes, coronary heart disease, chronic obstructive lung disease and chronic kidney disease) as poor prognostic factors for COVID-19. 13 Despite the lack of data on the true prevalence and risk of COVID-19 in rheumatic disease patients, immunosuppressed status (the use of chemotherapy or conditions requiring immunosuppressive treatment) was not reported to be a risk factor and risk for adverse outcome. One patient with systemic sclerosis-associated interstitial lung disease (SSC-ILD) on tocilizumab and 7 patients on bDMARDs or ts-DMARDs who developed COVID-19 recovered uneventfully. [14] [15] [16] Nonetheless, at least 2 patients on rituximab 17 developed respiratory failure and 1 of them died despite treatment with tocilizumab. 18 In order to gather real-world data to inform treatment strategies and better characterize individuals at increased risk of infection, the COVID-19 Global Rheumatology Alliance has successfully de- Preclinical and limited clinical data suggested that hydroxychloroquine (HCQ) and chloroquine (CLQ) have antiviral activities against SARS-CoV-2. [23] [24] [25] In contrast, a small but randomized study from China in patients with mild to moderate COVID-19 treated with HCQ or placebo found no difference in recovery rates, 26 Once hospitalized, for some patients with COVID-19, death can occur within a few days, many with ARDS, and some with multiorgan dysfunction syndrome. 14 In those critically ill patients, there are both clinical signs and symptoms, as well as laboratory abnormalities, that suggest a CSS is occurring in response to the viral infection. According to data from the Chinese cohorts, patients with severe disease and requiring intensive care often show leucopenia, lymphopenia, significantly higher levels of C-reactive protein (CRP), IL-6, IL-10, and tumor necrosis factor-α (TNF-α). 29 In this setting, biologic drugs selectively blocking inflammatory cytokines, such as TNF-α inhibitors, anti-IL-6, anti-IL-1 and JAK inhibitors are currently employed in the treatment of severe cases of COVID-19 in an experimental manner or undergoing clinical trials (Appendix 2). Tocilizumab, has been shown effective in treating CSS, a common complication of chimeric antigen receptor-T cell therapy used for treating refractory acute lymphoblastic leukemia 30 and may be effective in Chinese COVID-19 patients with severe and critical disease. 31 Anti-IL-6R antibody is currently included in the treatment recommendation for Chinese COVID-19 patients (Appendix 2). These concepts have led to interests in JAK inhibitors, for example baricitinib, as potential treatments for CSS complicated with severe COVID-19. ACE2 is a cell-surface protein widely existing on cells in the heart, kidney, blood vessels, especially alveolar epithelial cells. SARS-CoV-2 was believed to invade and enter lung cells through ACE2-mediated endocytosis. One of the known regulators of endocytosis is the AP2- The following link s are from national or international or ganiz ations to help rheumatologis t s an d patient s to manage their diseases during COVID -19 Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with Scientific and ethical basis for social-distancing interventions against COVID-19 Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis The effect of electronic cigarette and tobacco smoke exposure on COPD bronchial epithelial cell inflammatory responses Smoking upregulates angiotensin-converting enzyme-2 receptor: a potential adhesion site for novel coronavirus SARS Trends in cigarette smoking among older male adults in China: an urban-rural comparison Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA) Risk of stroke associated with use of nonsteroidal anti-inflammatory drugs during acute respiratory infection episode Acute respiratory infection and use of nonsteroidal anti-inflammatory drugs on risk of acute myocardial infarction: a nationwide case-crossover study Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis Risks related to the use of non-steroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients Non-steroidal anti-inflammatory drugs and covid-19 Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): facts and myths COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies What is the true incidence of COVID-19 in patients with rheumatic diseases? Rituximab for granulomatosis with polyangiitis in the pandemic of COVID-19: lessons from a case with severe pneumonia Incidence and clinical course of COVID-19 in patients with connective tissue diseases: a descriptive observational analysis Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19) No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine Clinical and immunologic features in severe and moderate Coronavirus Disease Management of cytokine release syndrome related to CAR-T cell therapy Effective treatment of severe COVID-19 patients with tocilizumab Baricitinib as potential treatment for 2019-nCoV acute respiratory disease Baricitinib for COVID-19: a suitable treatment? Lancet Infect Dis European League Against Rheumatism (EULAR) guidance for patients on COVID German Society for Rheumatology -Patient section guida nce-on-shiel ding-and-prote cting-extre mely-vulne rable-perso ns-from-covid-19/guida nce-on-shiel ding-and-prote ctingextre mely-vulne rable-perso ns-from-covid-19) National Rheumatoid Arthritis Society: Coronavirus: What we know so far Telemedicine Practice Guidelines (ncov)-infec tion-is-suspe cted National Institute of Health treatment guideline https://covid 19tre atmen tguid elines.nih.gov/intro ducti on/ US Food and Drug Administration (FDA) cautions against the use of antimalarial agents outside hospital setting or clinical trial: https:// www.fda.gov/drugs/ drug-safety-and-avail abili ty/fda-cauti ons-again st-use-hydro xychl oroqu ine-or-chlor oquine-covid-19-outsi de-hospi tal-setti ng-or Treatment recommendation for Chinese COVID-19 patients Hydroxychloroquine for the Treatment of Patients with Mild to Moderate COVID-19 to Prevent Progression to Severe Infection or Death The COVID-19 Global Rheumatology Alliance