COVID‐19 and rheumatology: Reflecting on the first wave and preparing for the second wave

Abstract

Cases of COVID-19 and associated hospitalizations are rising again, and we are at the start of a “second wave”. As we prepare for the second wave, we must reflect on what we have learned from the first and how we are going to effectively manage rheumatology patients going forward. Rheumatology patients were thought to be at a higher risk of contracting COVID-19 due to their disease and associated immunosuppressive treatments. In March, the British Society of Rheumatology developed a risk stratification tool to identify patients who were to shield during the height of the pandemic.1 Shielding precautions included staying home or within 2 m of other individuals when in public. Patients deemed to be at high risk were those on high-dose corticosteroids, cyclophosphamide and 2 immunosuppressive agents. Although shielding can reduce the risk of contracting COVID-19 we must also consider the psychosocial impact it has. Shielding renders patients to extreme isolation and rheumatology patients are already at higher risk of mental health disorders due to the challenges and chronicity of their disease. Superimposed social restrictions make them even more vulnerable to loneliness, depression and anxiety.2 In addition, denying them access to gyms and swimming pools which is a key part of managing arthritis, can cause exacerbation of symptoms. Another vital part of management are immunosuppressant drugs. When the pandemic began there was a theoretical risk that these drugs could increase the risk of developing severe COVID-19. Therefore, there was a hesitation in the rheumatology community to initiate disease-modifying antirheumatic drugs (DMARDs) in newly diagnosed rheumatic patients. However, since the start of the pandemic now pathophysiology of COVID-19 has come to light. It is thought the virus drives a “cytokine storm” leading to a hyper-inflammable state observed in conditions such as rheumatoid arthritis and lupus.3 It is therefore postulated that some of the immunosuppressive therapies used to treat rheumatic conditions are protective against COVID-19.4 An observational study demonstrated that rheumatic patients did not have a higher risk of contracting COVID-19 and they did not suffer a more aggressive illness than the general population. Rather, outcome is more dependent on age and co-morbidities.5 A case series revealed that baseline use of biologic therapy does not lead to worse outcomes compared to the general population.6 More recently, the RECOVERY trial in the United Kingdom has demonstrated that the use of steroid dexamethasone, reduces 28-day mortality in COVID-19 patients with an oxygen requirement.7 The interleukin (IL)-6 inhibitor tocilizumab has shown some benefit in observational studies in reducing mortality and invasive ventilation and is currently part of RECOVERY trial phase 2. Cumulative evidence so far suggests there may be a role for tocilizumab in controlling the cytokine storm induced by COVID-19 and it can have a protective factor in the rheumatoid cohort, but research is still ongoing, and the definite effect of tocilizumab is still yet to be determined. Furthermore, cohort studies in France have shown that anakinra, an IL-1 receptor antagonist, reduces the need for invasive ventilation in COVID-19 patients.8 Barcitinib, a Janus-activated kinase inhibitor and canakinumab, a monoclonal antibody of IL-1B have been shown to improve oxygenation in severe COVID-19 infection.9,10 There is a wealth of data suggesting that immunosuppressive therapy may be influential in downregulating the cytokine storm and in turn be protective against severe infection. Early aggressive treatment of inflammatory conditions, especially rheumatoid arthritis, leads to a better long-term prognosis and having untreated overt inflammation can itself cause immunocompromise.11 Current practice involves discussing the risks and benefits of starting DMARDs with patients and if they are agreeable then to favor drugs that have a shorter half-life such as hydroxychloroquine or sulfasalazine.12 For biologics, guidelines suggest switching from intravenous to subcutaneous or oral where possible to reduce hospital attendance. Additionally, they advise patients who have suspected or confirmed COVID-19, to continue hydroxychloroquine and sulfasalazine but suspend all other DMARDs.13 However, for COVID-free patients who are already established on DMARDs, stopping treatment abruptly will lead to a disease flare which will inevitably impact on their function. Therefore, many centers continued therapy for stable patients throughout the first wave. The risk of abruptly stopping DMARDs could cause hospitalization and requirement for high-dose systemic steroids ultimately leading to poorer disease outcomes.14 As COVID-19 cases are rising and lockdown measures are being reintroduced, it is necessary to consider the long-term plan for rheumatology patients based on what we have learned from the first wave. The drawbacks of shielding are extensive and there is no reproducible evidence that rheumatology patients are at increased risk of