Managing rheumatic diseases during COVID-19

Abstract

Rheumatology practice, during Coronavirus Disease 2019 (COVID-19) pandemic, has faced multifaceted challenges. Rheumatologists routinely prescribe immunosuppressant medications to their patients with multisystem autoimmune rheumatic diseases who are concerned about the increased risk of acquiring COVID-19 infection and are anxious to know if they should continue or hold these medications. Rheumatologists are often inundated by calls from their patients and physician colleagues caring for COVID-19 patients in hospitals, about how to manage the immunosuppression. Physicians face the challenging task of keeping up with the most up-to-date information on COVID-19. There are uncertainties about the mode of spread, clinical features, management options as well as long-term complications of COVID-19. Data are rapidly evolving and different studies on treatment options are showing contradictory results. It is known that viral illnesses can trigger a flare-up of underlying rheumatic disease that was previously in remission. To further complicate the scenario, some of the immunosuppressants have shown to have antiviral properties. This has created dilemma in the light of current COVID-19 crisis, as whether to continue or stop the immunosuppressive agents which could be essential to prevent complications of the rheumatic diseases including organ failure but also there is concern about acquiring COVID-19 or developing serious infection. Until we get an effective vaccine, immunosuppressant management for rheumatic diseases as well as other autoimmune diseases and transplants will pose difficult questions. This article is an attempt to review and understand COVID-19 and its impact on the immune system with special emphasis on managing medications used for autoimmune rheumatic diseases. We have provided general guidance about decision making, in regards to the immunosuppressive agents used in rheumatology practice with an understanding that this may change in near future.

Keywords: Autoimmune; COVID-19; DMARD; Immunosuppressive; Medications; Rheumatic.

Fig. 1

SARS-CoV2 port of entry is mostly at lungs and GI tract. As the virus infects the epithelium it gets endocytosed and the virus goes through proteolysis releasing its RNA (ribonucleic acid) at EPR (endoplasmic reticulum). With proteolysis, RNA is turned into amino-acids and gets reassembled with structural proteins at Golgi apparatus. After reassembly in cells, it gets exocytosed by cells at pulmonary/gastric epithelium. These reassembled viruses are ready to infect neighboring cells

Fig. 2

Immune Response to SARS-CoV2 & pharmacodynamics of rheumatology medications. This figure depicts (1) body’s immune response to SARS-CoV2 and (2) rheumatology meds (commonly prescribed) working at different levels. Cells—NK cells (null killer cells); APC, antigen presenting cell; enzyme/cytokines, COX-1, COX-2 = cyclo-oxygenase 1, 2; IL-2, 6, 12 = interleukin 2, 6, 12; IFN, interferon A&B; medications—CQ/HCQ, chloroquine/hydroxychloroquine; NSAIDS, nonsteroidal anti-inflammatory drugs; TLR/RLR, Toll-like receptor/retinoic acid inducible gene–like receptor (within macrophage); JAK/STAT pathway, Janus kinase/signal transducer and activation of transcription (depicted within T-helper cell). Immune response—Virus infection triggers innate immune response at site of infection (left side of figure); whereas the adaptive immune response (right side of dendrites/macrophage) occurs at lymphatic system. Each figure depicts various cells and its secretion. SARS-CoV2 infection triggers both innate and adaptive immunity. With innate immune response, the tissue injury/host infected cell is recognized by neutrophils, NK (null killer cells), macrophages, dendritic cells. Innate immunity focus on preventing instant spread of infection by recruiting more neutrophils, macrophages and NK cells. Dendritic and macrophage cell conveys message to antigen presenting cells, which in turn recruits pluripotent T cell. This pluripotent T cell secretes IL-12 (interleukin-12) and in turn gets differentiated into T-helper (CD4), cytotoxic T cell (CD8) and B cell. T-helper secrets IL-2 (interleukin-2) and IFN (interferon), whereas cytotoxic secrete IFN A, B (interferon A, B) and IL-12 (interleukin-12). Pharmacodynamics—red color–dotted lines indicate inhibition action of medications at specific site in a cell. Corticosteroids—inhibits phospholipase and thereby inhibiting leukotrienes, cycle-oxygenase production leading to less inflammation. NSAIDS—inhibits COX-2/ specific ones COX-1. CQ/HCQ (chloroquine/hydroxychloroquine)—inhibits Toll receptor/RLR receptors at intracellular level within macrophage, leading to decreased IFN production. Baricitinib—inhibits JAK/STAT pathway within T-helper cells, leading to further deactivation of adaptive immunity. Toclizumab—inhibits Interleukin-6 production by dendritic cells further delaying recruitment and inflammation