Anti-Rheumatic Drugs May Ameliorate the Clinical Course and Outcome of COVID-19 In Rheumatoid Arthritis Patients.

Current data demonstrated that in patients with coronavirus disease-19 (COVID-19), there is a dysregulation of the immune system during the severe form of the disease. This dysregulation is expressed with an uncontrolled release of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-17, tumour necrosis factor alpha (TNFa) and chemokines, associated with increased serum ferritin levels and other acute phase reactants. On the other side, these cytokines play a pivotal role in autoimmune rheumatic diseases (ARD), mostly in rheumatoid arthritis (RA) and the spondyloarthropathies. Patients affected with ARD represent a particular vulnerable group, considering that they may be in an immunocompromised status due to their ailment and its treatment on one side, but on the other side, they may be protected from their immunosuppressive therapy. To this end, we present five patients with RA treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and biologic (b) DMARDs who were affected from COVID-19 and we will try to give answers to the above hypothesis.

Treatment strategies of COVID-19: A rheumatology perspective.

The clinical progression of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to critical illness is associated with a systemic and uncontrolled inflammatory response of the innate and adaptive immunity with the release of a plethora of proinflammatory cytokines termed "cytokine storm". In the absence of an effective treatment, many off-label agents from the armamentarium of rheumatology are used. Here, from the perspective of a rheumatologist, we will discuss the current therapeutic strategies in critically ill patients with SARS-CoV-2 pneumonia. Thus, we will discuss the agents that aim to target viral entry and its replication into the host cell and those focusing and targeting the inflammatory response. In this setting, many agents have been used with promising results but, not all have been approved by the International Authorities and Institutions. In the first step (viral entry), SARS-CoV-2 monoclonal antibodies and remdesivir have been approved to be used and, in the second step, corticosteroids along with interleukin-6 inhibitors, or Janus Kinase inhibitors are currently used.

Colchicine Against SARS-CoV-2 Infection: What is the Evidence?

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of concern worldwide and a huge challenge for rheumatologists. Indeed, several antirheumatic drugs are currently used at different stages of COVID-19, such as several cytokine inhibitors and colchicine. Colchicine is one of the oldest medicines with potent anti-inflammatory properties. In rheumatic diseases it is widely used for the treatment of gout, calcium pyrophosphate deposition disease, and familial Mediterranean fever. It is also used off-label in cardiology to treat atrial fibrillation, pericarditis, and myocardial infarction. Over the last few years, advances in the understanding of colchicine's mechanism of action and its pharmacology and safety have made colchicine a promising candidate agent for the fight against COVID-19. In this review, we discuss COVID-19 pathophysiology highlighting colchicine's mode of action, its pleiotropic effects on neutrophils, inflammasome inhibition, and its viral activity. Finally, we discuss the main clinical studies dealing with the use of colchicine in COVID-19. Given the large body of evidence that demonstrates its effectiveness, safety, and its simple way of administration, colchicine seems to be a promising drug to reduce the risk of severe COVID-19 disease.

Anti-Rheumatic Drugs for the Fight Against the Novel Coronavirus Infection (SARSCoV-2): What is the Evidence?

SARS-CoV-2 is a positive-sense single-stranded RNA virus that causes the COVID-19 infection. Spike proteins are the most important proteins found on its capsule using the host's ACE2 receptors to invade respiratory cells. The natural course of the COVID-19 infection is variable, from asymptomatic to severe and potentially fatal. A small percentage of the severely infected patients will end up in an intensive care unit for ventilatory support. Elderly male patients with pre-existing medical conditions and smokers are at a disproportionate high risk to develop severe complications. Studies have shown that deaths occur due to a dysregulated immune system that overreacts, producing a plethora of cytokines, leading to the so-called "cytokine storm" phenomenon. In this direction, many drugs that are used in the everyday practice of Rheumatologists have been used. Indeed, pro-inflammatory cytokines such as the IL-1 and IL-6 have been shown to be the pivotal cytokines expressed, and anti-cytokine treatment has been tried so far with various results. In addition, hydroxychloroquine, an antimalarial drug, has been shown to reduce COVID-19 symptoms. Other drugs have also been used, such as intravenous pulses of immunoglobulins, and colchicine. Robust clinical trials are needed in order to find the suitable treatment. Current data indicate that hydroxychloroquine and cytokine targeting therapies may prove helpful in the fight of SARS-CoV-2 in appropriately selected patients.

Seronegative Erosive Arthritis Following SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting mostly the respiratory system, but several other organs and systems can be involved. Extrapulmonary manifestations and autoimmune phenomena following SARS-CoV-2 infection are frequent events occurring during the first 2 weeks or in later stages of the disease course. These can be expressed as an isolated discovery of autoantibodies, mostly antinuclear or antiphospholipid antibodies, through to full-blown autoimmune organ-specific and systemic diseases. Joint pain is a frequent complain in most patients, but to our knowledge, frank arthritis has not been reported so far. A 46-year-old woman developed symmetrical polyarthritis 2 months after SARS-CoV-2 infection. Laboratory tests showed high acute phase reactants, while the immunological profile was negative. Hand and wrists X-rays revealed soft tissue swelling as well as bone erosions at the ulnar base of the third and fourth metacarpophalangeal joint of the right hand and carpal bones. The patient responded well to small doses of prednisone and methotrexate and after 4 months she had a sustained clinical and laboratory improvement. This is the first report making an association between SARS-CoV-2 infection and erosive polyarthritis. Physicians dealing with patients infected from SARS-CoV-2 should be aware for the possible development of musculoskeletal disorders, among them symmetrical polyarthritis. Thus, a close follow-up and monitoring is mandatory.

COVID-19 in patients with gout on colchicine.

Current data demonstrated that severe cases of coronavirus-disease-19 (COVID-19) require treatment with antiviral therapy, dexamethasone, supportive care, as well as some anti-rheumatic drugs, among them, cytokine inhibitors and colchicine. Colchicine is an anti-inflammatory drug that is being used in rheumatology for many years to treat mostly gout, calcium pyrophosphate deposition disease, and Familial Mediterranean Fever. Here, we present for the first time, two patients suffering from gout being treated with colchicine, who were affected from severe acute respiratory coronavirus-2 (SARS-CoV-2) syndrome. Both patients presented with mild symptoms of COVID-19 expressed with myalgias, arthralgias, and sore throat, while laboratory investigations showed only high acute phase reactants. Four weeks later, both patients were free of symptoms with negative SARS-CoV-2 tests and without any complications. To our knowledge, there are no other studies of gout arthritis and SARS-CoV-2 infection published so far. Thus, our preliminary conclusion is that chronic use of colchicine may mitigate the clinical picture and disease course of COVID-19 in gout arthritis patients. Further studies with a large number of patients are needed to confirm the above beneficial effect of colchicine.

Use of conventional synthetic and biologic disease-modifying anti-rheumatic drugs in patients with rheumatic diseases contracting COVID-19: a single-center experience.

To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February-December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient's needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.