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1.
Lancet Rheumatol ; 3(6): e447-e459, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1307285

ABSTRACT

The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

2.
Pediatr Rheumatol Online J ; 19(1): 68, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1216904

ABSTRACT

BACKGROUND: SARS-CoV-2 can induce an immune impairment and dysregulation, finally resulting in the massive release of inflammatory mediators (cytokine storm), strongly contributing to the pulmonary and systemic manifestations in severe coronavirus disease 2019 (COVID-19). As a consequence, different drugs active on the immune system have been proposed for the treatment of the disease in adults. ROLE OF THE ANTI-RHEUMATIC AGENTS IN CHILDREN: Children are more likely to develop a mild disease course, as the severe form of COVID-19 is identified in less than 5% of the pediatric patients. Moreover, in children a peculiar disease phenotype, defined as multisystem inflammatory syndrome in children (MIS-C) is observed, representing the most severe expression of the inflammatory dysregulation caused by SARS-CoV-2. The limited experience with the severe pediatric COVID-19 and MIS-C does not allow conclusions about the role of the immune pharmacological approach, and therefore the treatment of these conditions represents a considerable clinical challenge. The use of chloroquine, hydroxychloroquine, and colchicine in the early disease stages is not sufficiently supported by evidence, and there is an increasing interest in the role of biologic agents, including anti-IL-1 and anti-IL-6 agents, in the prevention and treatment of the severe manifestations of COVID-19. CONCLUSION: The therapeutic approach to pediatric COVID-19 is multidisciplinary, and anti-rheumatic agents have a prominent role in severe disease. This paper reviews the rationale for the use of anti-rheumatic agents in pediatric COVID-19 and MIS-C and the clinical experience with the single drugs. Finally, the areas of potential improvement in the use of anti-rheumatic agents, including the optimization of the drug choice and the timing of administration, are discussed.


Subject(s)
Antirheumatic Agents/pharmacology , Biological Factors/pharmacology , COVID-19 , Systemic Inflammatory Response Syndrome , COVID-19/complications , COVID-19/drug therapy , COVID-19/immunology , COVID-19/prevention & control , Child , Humans , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/prevention & control , Treatment Outcome
3.
Rheumatol Int ; 41(4): 811-817, 2021 04.
Article in English | MEDLINE | ID: covidwho-1092075

ABSTRACT

Coronavirus disease 2019 (COVID-19) refers to the clinical picture of an important and severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Considering the current knowledge on the pathophysiology and clinical manifestations of COVID-19, it is safe to state that both COVID-19 and inflammatory rheumatic disorders cause a cytokine storm and merit treatment with anti-rheumatic drugs. Three patients, who were on regular follow-up due to the diagnosis of familial Mediterranean fever (FMF), contracted COVID-19 infection; and their pre-clinical and post-clinical data as well as laboratory, prognosis and treatment data were investigated. Effects of colchicine in FMF patients who contracted COVID-19 infection were presented in this study. All the cases recovered from COVID-19 without complications. The present study suggests that colchicine can positively affect the prognosis of COVID-19 in FMF patients; therefore, experience of rheumatologists in the use of anti-inflammatory drugs can be highly instrumental in management of COVID-19 patients.


Subject(s)
COVID-19/drug therapy , Colchicine/therapeutic use , Familial Mediterranean Fever/drug therapy , SARS-CoV-2 , Adult , Aged , COVID-19/immunology , Female , Humans , Interleukin-1/antagonists & inhibitors , Male , Middle Aged , Prognosis
4.
Best Pract Res Clin Rheumatol ; 35(1): 101659, 2021 03.
Article in English | MEDLINE | ID: covidwho-1060265

ABSTRACT

Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable examples include corticosteroids, interleukin 6 (IL-6), interleukin 1 (IL-1), Janus kinase (JAK), and tumor necrosis factor alpha (TNF-α) inhibitors. The aim of this narrative review is to analyze the mechanistic rationale and available evidence for these selected anti-rheumatic drugs for the treatment of COVID-19. Currently, only corticosteroids have consistently proven to be effective in decreasing mortality and are recommended in clinical guidelines for the treatment of severe and critical COVID-19. Multiple randomized controlled trials (RCTs) are ongoing to determine the role of other immunosuppressants.


Subject(s)
Antirheumatic Agents , COVID-19 , Rheumatic Diseases , Antirheumatic Agents/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Rheumatic Diseases/drug therapy , SARS-CoV-2
5.
Front Pharmacol ; 11: 569849, 2020.
Article in English | MEDLINE | ID: covidwho-972744

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the "cytokine storm." Among these, interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1ß seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF-α, and IL-1ß in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

6.
Reumatologia ; 58(5): 261-264, 2020.
Article in English | MEDLINE | ID: covidwho-934576
7.
Clin Rheumatol ; 40(5): 2047-2055, 2021 May.
Article in English | MEDLINE | ID: covidwho-898035

ABSTRACT

INTRODUCTION/OBJECTIVE: The general public may utilize online information through search engines for implications and risks of some anti-rheumatic drugs. These drugs have been used in the management of coronavirus disease 2019 (COVID-19) and associated inflammatory sequelae or cytokine storm of infection. Therefore, the objective of this study was to investigate the population-level interest in anti-rheumatic drugs during the COVID-19 era, by analyzing changes in Google search frequency data. METHOD: To obtain the relative search volume (RSV) of anti-rheumatic drugs, we queried Google Trends for 78 search terms representing non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, antigout agents, conventional disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, biologics, and Janus kinase (JAK) inhibitors within the USA. Three 8-week periods in 2020 (March 15-May 9), (May 10-July 4), and (July 5-August 29) representing the initial- and short-term periods were compared to overlapping periods of the preceding 3 years (2017-2019). RESULTS: We found statistically significant increases in RSV for colchicine, hydroxychloroquine, tocilizumab (and its brand name-Actemra), and anakinra, and statistically significant decreases among brand names of immunosuppressive agents (i.e., mycophenolate mofetil, azathioprine, cyclophosphamide, tacrolimus, cyclosporine) during both the initial- and short-term COVID-19 periods as compared to overlapping periods of the preceding 3 years. CONCLUSION: There were significant increases in RSV of colchicine, hydroxychloroquine, tocilizumab, and anakinra during both initial- and short-term COVID-19 periods when compared to overlapping periods of the preceding 3 years reflecting a heightened level of information-seeking on these drugs during the pandemic. Rheumatologists should address this increase in informational demand. Further research assessing medium- and long-term interest in anti-rheumatic drugs is required to increase our knowledge on this new pandemic. Key Points •This study was aimed to investigate the population-level interest in anti-rheumatic drugs in the COVID-19 era, by analyzing changes in Google search frequency data. •Significant increases were seen in relative searches for colchicine, hydroxychloroquine, tocilizumab, and anakinra during both initial and short-term COVID-19 periods when compared to similar periods of 2017-2019 reflecting a heightened level of information-seeking on these drugs during the pandemic. •Rheumatologists should address this increase in informational demand for colchicine, hydroxychloroquine, tocilizumab, and anakinra.


Subject(s)
Antirheumatic Agents , COVID-19 , Antirheumatic Agents/therapeutic use , Humans , Hydroxychloroquine , Pandemics , SARS-CoV-2
9.
J Popul Ther Clin Pharmacol ; 27(S Pt 1): e14-e25, 2020 06 27.
Article in English | MEDLINE | ID: covidwho-638400

ABSTRACT

COVID-19 disease is the most recent pandemic, since it has affected more than four and a half million people and caused more than 300,000 deaths. It is a very complex systemic disease in terms of pathogenesis, treatment, and prognosis. Pharmacological treatment may include antiviral and antimalarial drugs, antibiotics, monoclonal antibodies, corticosteroids as well as low-molecular-weight heparins to prevent the evolution of the disease from reaching the severe inflammatory phase that can lead to respiratory complications, multiple organ failure, disseminated intravascular coagulation (DIC), and finally death. Therefore, pending the development of the much sought-after vaccine, there needs to be a multidisciplinary approach to tackling this disease, and it is essential to use different medical treatments at the correct pathogenic moment. The aim of this article is to evaluate the rationale and reason behind the use of antirheumatic drugs, by expert point of view, in the various phases of the disease. Another important aspect in the management of the disease is to identify patients at high risk, both to change their lifestyle and to correct the state of their health through non-pharmacological measures for improving their immuno-balance. Our literature review reveals the important role and the therapeutic potential of antirheumatic agents in preventing the progression of the disease and aiding recovery from the disease. However, there is a lack of clinical evidence to support the use of these agents, indicating that further randomized controlled studies are required.


Subject(s)
Antirheumatic Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal/therapeutic use , Antimalarials/therapeutic use , COVID-19 , Coronavirus Infections/pathology , Humans , Pandemics , Pneumonia, Viral/pathology
10.
Rheumatol Int ; 40(8): 1193-1213, 2020 08.
Article in English | MEDLINE | ID: covidwho-526706

ABSTRACT

COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2, is a global public health issue threatening millions of lives worldwide. Although the infection is mild in most of the affected individuals, it may cause severe clinical manifestations such as acute respiratory distress syndrome or cytokine storm leading to death. Children are affected less, and most experience a milder disease. As rheumatologists, we deal with the uncontrolled response of the immune system, and most of the drugs we use are either immune modulators or immunosuppressants. Thus, the rheumatologists participate in the multidisciplinary management of COVID-19 patients. On the other hand, our patients with rheumatic diseases constitute a vulnerable group in this pandemic. In this review, a systematic literature search was conducted utilizing MEDLINE/PubMed and Scopus databases, and 231 COVID-19 patients with rheumatic diseases have been identified. Only one of these patients was a child. Among these, 9 (3.9%) died due to COVID-19. In light of the current data, the aspects of COVID-19 resembling rheumatic diseases, the possible reasons for why children are affected less severely, the hypothetic role of available vaccines in preventing COVID-19, the unique position of patients with rheumatic diseases in this pandemic, and the use of anti-rheumatic drugs in COVID-19 treatment are discussed.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Rheumatic Diseases/drug therapy , BCG Vaccine/immunology , COVID-19 , Child , Coronavirus Infections/prevention & control , Female , Humans , Male , Measles-Mumps-Rubella Vaccine/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2
12.
Autoimmun Rev ; 19(5): 102523, 2020 May.
Article in English | MEDLINE | ID: covidwho-13932

ABSTRACT

The outbreak of the new coronavirus infections COVID-19 in December 2019 in China has quickly become a global health emergency. Given the lack of specific anti-viral therapies, the current management of severe acute respiratory syndrome coronaviruses (SARS-CoV-2) is mainly supportive, even though several compounds are now under investigation for the treatment of this life-threatening disease. COVID-19 pandemic is certainly conditioning the treatment strategy of a complex disorder as rheumatoid arthritis (RA), whose infectious risk is increased compared to the general population because of an overall impairment of immune system typical of autoimmune diseases combined with the iatrogenic effect generated by corticosteroids and immunosuppressive drugs. However, the increasing knowledge about the pathophysiology of SARS-CoV-2 infection is leading to consider some anti-rheumatic drugs as potential treatment options for the management of COVID-19. In this review we will critically analyse the evidences on either positive or negative effect of drugs commonly used to treat RA in this particular scenario, in order to optimize the current approach to RA patients.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/immunology , Betacoronavirus , Coronavirus Infections/drug therapy , Immunocompromised Host , Pneumonia, Viral/drug therapy , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/virology , COVID-19 , China , Coronavirus Infections/complications , Humans , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2
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