Int J Rheum Dis. 2020;23:613-619. | 613 wileyonlinelibrary.com/journal/apl 1 | INTRODUC TI ON The present world is experiencing a pandemic (coronavirus disease-19 or COVID-19) caused by a novel strain of coronavirus, called SARS-CoV-2, previously called 2019-CoV. At the time of writing this article, 3 72 757 cases spanning over 195 countries and territories and 1 international conveyance have been reported. 1 This could be an underestimate due to the lower number of diagnostic tests and case identification partly due to poor health services in most countries. The mortality rate stands at 0.5-4.4% 2 ;however, this could be an overestimate as the exact denominator of actual number of cases is underreported. Diversion of all healthcare facilities toward the COVID-19 pandemic is likely to increase the morbidity and mortality due to other health problems. AbstractObjective: The pandemic coronavirus disease-19 (COVID-19) has pushed the global healthcare system to a crisis and amounted to a huge economic burden. Different drugs for prophylaxis against COVID-19 including chloroquine (CQ) or hydroxychloroquine (HCQ) have been tried. This study was performed to systematically review the role of CQ and HCQ in preventing the spread of COVID-19. Methods: PubMed, EMBASE, ClinicalTrials.gov, International Clinical Trials Registry Platform and Cochrane Library databases were searched for studies that evaluated the prophylactic role of CQ or HCQ on SARS-CoV-2 (pre-clinical studies) or COVID-19 (clinical studies) until 30 March 2020. The available literature was critically appraised. Results: A total of 45 articles were screened and 5 (3 in vitro pre-clinical studies and 2 clinical opinions) were included. The pre-clinical studies showed the prophylactic effects of CQ and HCQ against SARS-CoV-2. On the other hand, the clinical opinions advocated the prophylactic use of CQ and HCQ against COVID-19. However, no original clinical studies on the prophylactic role of CQ or HCQ on COVID-19 were available.Conclusion: Although pre-clinical results are promising, to date there is a dearth of evidence to support the efficacy of CQ or HCQ in preventing COVID-19. Considering potential safety issues and the likelihood of imparting a false sense of security, prophylaxis with CQ or HCQ against COVID-19 needs to be thoroughly evaluated in observational studies or high-quality randomized controlled studies. K E Y W O R D Schloroquine, COVID-19, high-risk, hydroxychloroquine, prevention, SARS-CoV-2

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection. Keywords Coronavirus disease-2019 (COVID-19) • Rheumatic musculoskeletal diseases (RMDs) • Autoimmunity • Rheumatology Abbreviations AAV Anti-neutrophil cytoplasmic antibodyassociated vasculitis ACE2 Angiotensin-converting enzyme 2 ANA Antinuclear antibodies AIDS Acquired immunodeficiency syndrome APCs Antigen-presenting cells APS Antiphospholipid antibody syndrome ARDS Acute respiratory distress syndrome CAHA Coronavirus-associated hemostatic lung abnormality CART Chimeric antigen receptor T cell CCL2 Chemokine (C-C motif) ligand 2 CK Creatine kinase COVID-19 Coronavirus disease-2019 CSF Cerebrospinal fluid CRS Cytokine release syndrome CXCL8 C-X-C motif chemokine ligand 8 DADA-2 Deficiency of adenosine deaminase-2 DIC Disseminated intravascular coagulation Rheumatology INTERNATIONAL Sanket Shah and Debashish Danda have contributed equally as first authors.

Prepared from the collective plasma of several thousand people, therapeutic intravenous immunoglobulin (IVIg) consists mostly of human polyspecific IgG. In addition to its use in primary and secondary immune deficiencies, IVIg is used in the treatment of several rheumatic conditions, including Kawasaki disease, dermatomyositis and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. In these diseases, IVIg therapy generally involves the use of 2 g/kg administered over either 2 or 5 consecutive days. However, dosage regimens have not been thoroughly explored, and indications for IVIg in most rheumatic diseases, such as systemic lupus erythematosus, polymyositis and catastrophic antiphospholipid syndrome, derive from its off-label usage. Randomized clinical trials are warranted to support the evidence-based use of IVIg, and to identify the ideal administration protocols to maximize the benefits of what is a limited resource. Further research to improve the therapeutic application of IVIg relies essentially on the conception of next-generation immunoglobulin preparations and optimization of combined therapies with immunomodulatory drugs and biologic agents.

Limited information is available on the prevalence of gallstones in the first-degree relatives of gallstone patients. Three groups of subjects were studied by real-time ultrasound examination: group A, 105 index gallstone patients (male/female; 20:85); group B, 330 first-degree relatives of index patients; group C, matched controls for group A (n = 105) and group B (n = 330) subjects. Dietary, anthropometric, and biochemical investigations were carried out. In 39 of 105 (37%) index cases, one or more additional family members had gallstones (positive-index case). The positive-index cases were younger than the remaining index cases (mean age, 33.1 +/- 14 vs. 44.5 +/- 13.1 years; P < .05). Fifty-one of 330 (15.5%) first-degree relatives had gallstones, nearly four and a half times (95% confidence interval [CI], 2.4 to 8.5) more often than in the matched control population (12 of 330 [3.6%]). Thirty-three of 51 (65%) positive relatives were women; mother (37.3%), sister (17.6%) or daughters (10%) to the index patients. There was no difference in the diet, physical activity, and serum lipid profile between the positive index patients and the remaining gallstone patients and positive relatives and their controls. Our results show that there is a strong familial predisposition for gallstone formation. Female relatives of young gallstone patients should be routinely screened for gallstones.