Can Anti-TNFα Antibodies Affect SARS-CoV-2 Disease Outcomes? (original) (raw)
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The effect of drugs used in rheumatology for treating SARS-CoV2 infection
Expert Opinion on Biological Therapy, 2020
Introduction: SARS-CoV-2 is a novel coronavirus that was first isolated from a group of patients hospitalized with pneumonia in China at the end of 2019, and, in February 2020, the syndrome it caused was named coronavirus disease 2019 (COVID-19) by the World Health Organization. In the absence of specific antiviral treatments capable of neutralizing the etiological agent, one therapeutic approach is to control the cytokine storm responsible for the most severe forms of the disease. The characteristic cytokine profile of severely affected patients is increased levels of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor alpha (TNF-α). Areas covered: This article discusses the pathogenesis of COVID-19 as a rationale for using the biological and targeted synthetic drugs used in rheumatology (anti-TNF, anti-IL-1 and anti-IL-6 agents and baricitinib) to treat the disease, and provides key information concerning their potential benefits and adverse effects. Expert opinion: Interleukin inhibition seems to be a promising means of treating COVID-19 patients when respiratory function declines (or even earlier) if there are laboratory data indicating the presence of a cytokine storm because the interleukins are key drivers of inflammation. However, it is important to consider the risks and benefits of biological agents carefully, and critically analyze the evidence concerning their use in COVID-19 patients.
Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?
Pharmaceuticals
The study of cytokine storm in COVID-19 has been having different edges in accordance with the knowledge of the disease. Various cytokines have been the focus, especially to define specific treatments; however, there are no conclusive results that fully support any of the options proposed for emergency treatment. One of the cytokines that requires a more exhaustive review is the tumor necrosis factor (TNF) and its receptors (TNFRs) as increased values of soluble formats for both TNFR1 and TNFR2 have been identified. TNF is a versatile cytokine with different impacts at the cellular level depending on the action form (transmembrane or soluble) and the receptor to which it is associated. In that sense, the triggered mechanisms can be diversified. Furthermore, there is the possibility of the joint action provided by synergism between one or more cytokines with TNF, where the detonation of combined cellular processes has been suggested. This review aims to discuss some roles of TNF and ...
Arthritis Research & Therapy, 2020
BackgroundPrevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis.MethodsThe study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated.Resul...
Pre-exposure to anti-TNFα decreases COVID-19 symptoms: a multicentre retrospective cohort study
2020
AIM: Immune response hyperactivation is critical in the progression of coronavirus disease (COVID-19). We studied the effect of the pre-exposure to disease-modifying antirheumatic drugs (DMARDs) that decrease immunological responses on the incidence of COVID-19 symptoms to explore therapeutic approaches in its early stages. METHODS: Multicentre retrospective cohort study including 2,494 patients with inflammatory diseases recruited from 14 primary care centres in Barcelona (Spain). The primary outcome was the presence of confirmed or highly suspected COVID-19 (hsCOVID-19) symptoms reported during March 2020 at primary care or hospital emergency department. Multivariable Poisson regression models were fitted to estimate hsCOVID-19 symptoms relative risk (RR) adjusted by comorbidities. RESULTS: Biological (RR=0.46, CI95%=0.31-0.67) and synthetic (RR=0.62, CI95%=0.43-0.91) DMARDs used in immunomediated inflammatory diseases diminished the incidence of symptomatic cases of hsCOVID-19. Striking sex differences were revealed. Protective effects of anti-TNFα pre-exposure (RR=0.50, CI95%=0.33-0.75) were higher in women (RR=0.33, CI95%=0.17-0.647), whereas anti-IL6/12/17/23 compounds pre-exposure (RR=0.47, CI95%=0.24-0.92) produced slightly higher protective effects in men (RR=0.44, CI95%=0.15-1.68). Pre-exposure to low glucocorticoid doses also revealed sex differences decreasing the incidence of hsCOVID-19 symptoms predominantly in women (RR=0.72, CI95%=0.42-1.22). A merely protective effect of pre-exposure to chloroquine/hydroxychloroquine (RR 0.76, CI95%=0.36-1.62) was observed. CONCLUSION: We identified specific DMARDs with different immune-depressor mechanisms that decrease hsCOVID-19 symptoms with striking sex differences. These results underline the potential interest of starting clinical trials with anti-TNFα compounds in women to evaluate their efficacy in minimizing disease progression in the early stages of COVID-19.
Nature Communications
Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.
2021
We provide novel data on anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine(D210) in 828 autoimmune rheumatic diseases(ARD) patients compared with 223 age/sex-balanced control group(CG). From D69 to D210, anti-S1/S2IgG positivity and GMT reduced 23.8% and 38% in ARD(p<0.001/p<0.001) and 20% and 51% in CG(p<0.001/p<0.001). From D69 to D210 NAb positivity and activity declined 41% and 54% in ARD(p<0.001/p<0.001) and 39.7% and 47% in CG(p<0.001/p<0.001). Multivariate logistic regression analysis showed that male(OR=0.56;95%CI0.40-0.79;p<0.001), prednisone(OR=0.56; 95%CI0.41-0.76;p<0.001), anti-TNF(OR=0.66;95%CI0.45-0.96;p=0.031), abatacept(OR=0.29; 95%CI0.15-0.56;p<0.001) and rituximab(OR=0.32;95%CI0.11-0.90;p=0.031) use were associated with a substantial reduction on IgG response at D210 in ARD patients. A decrease of COVID-19 cases(from 27.5 to 8.1/100 person-years;p<0.001)...
Rheumatology International
Severe acute respiratory syndrome coranovirus-2 (SARS-CoV-2) infection has become an important health-care issue worldwide. The coronavirus disease 2019 (COVID-19) has also raised concerns among patients with inflammatory rheumatic conditions and their treating physicians. There are emerging data regarding the potential risks of SARS-CoV-2 for this particular patient group. However, less is known with regard to the course of COVID-19 among patients receiving IL-17 inhibitors. The aim of the current article is to review the growing body of knowledge on the course/management of COVID-19 in patients with inflammatory rheumatic diseases by presenting a SARS-CoV-2 infected case with ankylosing spondylitis under secukinumab therapy. A 61-year old patient with ankylosing spondylitis who was on secukinumab therapy for 5 months admitted with newly onset fever and gastrointestinal complaints. After being hospitalized, she developed respiratory manifestations with focal pulmonary ground-glass opacities and multiple nodular densities in both lungs. The patient was tested positive for SARS-CoV-2 infection. Substantial clinical improvement was obtained following a management plan, which included tocilizumab, hydroxychloroquine, prednisolone and enoxaparin sodium. PubMed/MEDLINE and Scopus databases were searched by using relevant keywords and their combinations. The literature search revealed four articles reporting the clinical course of COVID-19 in seven rheumatic patients on secukinumab. The clinical course of SARS-CoV-2 infection was mild in most of these patients, while one of them experienced severe COVID-19. Interleukin-17 has been related to the hyperinflammatory state in COVID-19 and IL-17 inhibitors were presented as promising targets for the prevention of aberrant inflammation and acute respiratory distress in COVID-19. However, this hypothesis still remains to be proved. Further studies are warranted in order to test the benefits and risks of IL-inhibitors in SARS-CoV-2 infected individuals.