COVID-19 and Systemic Lupus Erythematosus: Focus on Immune Response and Therapeutics

Abstract

The SARS-CoV-2 novel coronavirus has caused the COVID-19 pandemic with over 35 million cases and over a million deaths worldwide as of early October 2020. The populations most affected are the elderly and especially those with underlying comorbidities. In terms of race and ethnicity, black and hispanic populations are affected at disproportionately higher rates. Individuals with underlying conditions that cause an immune-compromised state are considered vulnerable to this infection. The immune response is an important determinant in viral infections including coronaviruses, not only in the antiviral defense but also in the disease progression, severity, and clinical outcomes of COVID-19. Systemic lupus erythematosus is a chronic autoimmune disease which also disproportionately afflicts black and hispanic populations. In lupus patients, an aberrant immune response is characterized by the presence of circulating autoantibodies, lymphopenia, aberrant T cells, and proinflammatory cytokines along with defective regulatory mechanisms, leading to immune-mediated damage to tissues. Lupus patients are often treated with immune-suppressants and therefore are immunecompromised and more susceptible to infections and may be vulnerable to coronavirus infection. While the anti-viral immune response is important to protect from coronavirus infection, an uncontrolled proinflammatory cytokine response can lead to cytokine storm which causes damage to the lungs and other organs, causing significant morbidity and mortality. Better understanding of the underlying immune response and therapeutic strategies in lupus and COVID-19 is important to guide management of this deadly infectious disease in the context of lupus and vice-versa.

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…Lymphopenia is a common feature of SLE, thought to be due to complement-mediated or antibody-dependent cytotoxicity, excess apoptosis, and decreased lymphopoiesis. 134 In addition, T cell function is also impaired in SLE, which may predispose these patients to infections (see the previous section on Relationship between SLE and risk of viral infections ). Reversible lymphopenia has been observed in patients with COVID-19, especially those with severe disease.…”

A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in COVID-19

“…According to rank (with a cut off score 4), the enriched known or reported comorbid conditions or long-term complications are lupus erythematosus (Rank-1) [100], depressive disorder / mental depression (Rank-2) [30, 101], hepatitis C (Rank-3) [102], breast cancer (Rank-4) [75], arthritis (Rank-5) [103], asthma (Rank-6) [10, 77], liver cancer (Rank-6) [78], tuberculosis (Rank-7) [104, 105], diabetes (Rank-8) [82], myocardial infarction (Rank-9) [35, 106], macular degeneration (Rank-9) [80], chronic kidney disease (Rank-9) [56, 57], arteriosclerosis (Rank-10) [107], ulcerative colitis (Rank-10) [108], liver cirrhosis (Rank-11) [12, 109], sepsis / septicaemia /septic shock (Rank-11) [60, 81], other autoimmune diseases (Rank-12) [49, 50], cerebrovascular accident / stroke (Rank-13) [110], congenital anemia (Rank-13) [111], COPD (Rank-13) [86], multiple myeloma (Rank-14) [112], hypertensive disease (Rank-14) [9, 113], dyslipidemia (Rank-15) [93], metabolic syndrome X (Rank-15) [51, 114], osteoporosis (Rank-16) [91], prostate cancer (Rank-17) [115], psoriasis (Rank-17) [116], leukemia (Rank-18) [117, 118], long QT syndrome (Rank-18) [119], dementia (Rank-18) [120], schizophrenia (Rank-18) [121], intellectual disability (Rank-18) [122, 123], diabetic kidney disease/ diabetic nephropathy (Rank-18) [124]etc.…”

Interferons and other cytokines, genetics and beyond in COVID-19 and autoimmunity

“…The SARS-CoV-2 certainly has the potential to manipulate the immune system. Indeed, lymphopenia has been described as a hallmark of the COVID-19 syndrome [ 24 , 25 ]. In fact, COVID-19 pathogenesis is regarded as immune asynchrony or immune cacophony [ [26] , [27] , [28] ].…”

“…Detection of autoantibodies, classically searched for in lupus patients. [ 25 , 28 , 44 , 45 , 48 ] Innate immune factors What is the role of neutrophils and neutrophil specific factors in COVID-19 and may these be modulated? Detection of neutrophil numbers and differentiation stages with the use of molecular markers (e.g.…”