CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.

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Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial.

Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) (p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness. The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine.

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Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey.

The approach of New Zealand’s Pharmaceutical Management Agency (PHARMAC) has much to commend it, say Jacqueline Cumming and colleagues

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How New Zealand has contained expenditure on drugs

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.

https://jitc.bmj.com/content/jitc/9/6/e002630.full.pdf

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies.

The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: a systematic review.

There is concern that people with rheumatic disease, often treated with immunosuppressive or immunomodulatory medication, may be at an increased risk of poor outcomes of novel coronavirus disease-2019 (COVID-19). However, hyperinflammation is a major cause of morbidity and mortality in COVID-19 and treatment with glucocorticoids has been shown to improve outcomes in patients with severe COVID-19. Therefore, uncertainty exists about continuing or withholding immune therapies with the risk of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review covers the current knowledge with respect to the risk of infection and outcomes and risk factors for poor outcomes in patients with rheumatic disease. We also discuss data from other immune-mediated diseases and its relevance to patients with rheumatic disease. In addition, we cover the limitations of the research efforts to date and how the current knowledge translates into practice guidance. Finally, we discuss our vision of the future research agenda.

Novel coronavirus disease-2019 (COVID-19) in people with rheumatic disease: Epidemiology and outcomes.

For the vast majority of the estimated 100,000 New Zealanders who suffer from rheumatoid arthritis (RA), relatively inexpensive disease-modifying antirheumatic drugs (DMARD) regimens are sufficient to control inflammatory disease and maintain long-term function. Some DMARDs have been shown to slow, but not arrest, the progression of erosions. All but a few of those who suffer from ankylosing spondylitis (AS) can manage full social participation with non-steroidal anti-inflammatory drugs (NSAIDs) and an exercise regimen. For the small subset of arthritis sufferers who have disabling pain and progressive damage from uncontrolled inflammatory disease, the advent of the biological era offered great promise. In most of the developed world, this promise is being delivered to patients with an expanding range of diseases including RA, AS, and psoriatic arthritis, but central government (PHARMAC) funding for TNF inhibitors in New Zealand has until recently been limited to etanercept for approximately 40 patients with juvenile inflammatory arthritis.

TNF inhibitors for inflammatory arthritis in New Zealand.

Ankylosing spondylitis (AS) is a chronic, progressive disease characterized by infl ammation in the spine and sacroiliac joints which causes pain, stiffness and the potential for spinal ankylosis. It is associated with signifi cant functional impairment. It is common and since onset is often in young people, the burden of disease is considerable. Conventional treatment including non-steroidal antiinfl ammatory drugs (NSAIDs) and physiotherapy have proven but limited effi cacy in controlling symptoms and preventing progression of spinal manifestations. Infl iximab, a chimeric monoclonal antibody which binds to and inhibits tumor necrosis factor alpha (TNFα), is highly effective in controlling disease activity in AS. In AS, infl iximab 5 mg/kg body weight is usually given as an infusion at weeks 0, 2 and 6, and then every 6-8 weeks. When infl iximab is used in combination with NSAIDs a rapid improvement in disease activity by at least 50% is seen in as many as 50% of AS patients. Infl iximab has been shown to have ongoing effi cacy for as long as regular infusions continue and is safe in the medium term. Magnetic resonance studies show major reductions in spinal infl ammation during treatment with infl iximab, however ongoing studies will assess if infl iximab has disease

Rebecca Grainger

Papers

Novel coronavirus disease-2019 (COVID-19) in people with rheumatic disease: Epidemiology and outcomes.

TNF inhibitors for inflammatory arthritis in New Zealand.

Infl iximab in the treatment of ankylosing spondylitis