key: cord-0687953-24z2cuag
authors: Elkhalifa, Shuayb; Chinoy, Hector
title: The Avalanche of Antirheumatic therapy and COVID-19 vaccinations
date: 2021-04-19
journal: Rheumatology (Oxford)
DOI: 10.1093/rheumatology/keab366
sha: 08706c1d242e4fd55cffbc18acf7de5bebc572f8
doc_id: 687953
cord_uid: 24z2cuag

nan

At the time of writing, there are three vaccines for COVID-19 authorised for emergency use in the UK by the Medicines and Healthcare Products Regulatory Agency, three for use in the US by the Food and Drugs administration, and four for use in the European Union by the European Medicines Agency. The Pfizer-BioNtech and Moderna vaccines are nucleosidemodified messenger RNA (mRNA) vaccines that use viral mRNA to provide the genetic code to allow host cells to produce the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral spike protein. 1, 2 The Oxford-AstraZeneca vaccine uses a replication deficient chimpanzee adenovirus vector to deliver the DNA sequence that codes for the SARS-CoV-2 viral spike protein to allow host cells to produce the viral spike protein. 3 Mounting an optimal immune response to COVID-19 vaccines requires effective activation and function from both T and B lymphocytes. 4, 5 Patients on immunosuppressive therapy may mount an unsatisfactory immune response following vaccination which could reduce vaccine effectiveness.

In this issue of the Journal, Arnold et al 6 was also preliminary data suggesting worse outcomes particularly in rituximab-treated COVID-19 patients. Conversely, anti-TNF therapy is associated with decreased odds of hospitalisation due to COVID-19. 7 Arnold et al 6 have focused on the effect of antirheumatic therapies on humoral immunity with less emphasis of cellular mediated immunity in the context of vaccines responses. T cells play a pivotal role in generating an effective antibody response and long term memory. 8 Whilst they acknowledged that most prior vaccine response studies largely investigated antibody titres post-vaccination 9 , effective vaccine candidates, particularly for viruses such as SARS CoV2, would also benefit from inducing effective cellular mediated immunity.

Furthermore, facilitating an optimal cytotoxic T cell effect is essential particularly when antibody responses fail to completely block viral infection or transmision 8 which has been the case with pathogens that are highly variable and/or cause persistent and latent infections such as human immunodeficiency virus, hepatitis C virus, and Mycobacterium tuberculosis. 8, 10 Thus, monitoring antibody levels alone as a marker of vaccine response may not accurately ascertain efficacy and protection.

Moreover, the pathogenic mechanisms of various rheumatic disorders and their impact on the immune system require special consideration. 11 The heterogeneity of these disorders and multifactorial interactions between different components of the immune systems and antirheumatic therapies may result in diverse clinical phenotypes and prognosis. 7 It is extremely difficult to apply the same approach to all patients with rheumatological disorders e.g. patients with systemic lupus erythematosus compared to rheumatoid arthritis or other connective tissue diseases. 11 The detailed advice with respect to individual drugs is welcome, the authors do stress that modification of therapy should not delay matters -the priority is to proceed with vaccination. Pending data on vaccine outcome in patients with or without prevaccine medication will also be important. Exploring the risks and benefits of treatments with patients to promote shared decision making and obtain informed consent is essential whilst the situation with COVID-19 pandemic and guidance is evolving with time.

Further understanding of the immune response to COVID-19 vaccines in the context of various antirheumatic medications is vital in formulating a logistic strategy for individuals with autoimmune and inflammatory disorders. More data is needed to understand the immune biomarkers for protection against COVID-19 vaccinations. Antibodies generally speaking are potential correlates of protection, although the protective role of cellular immunity and duration of both neutralising antibodies and cellular responses and the correlates of protection remain to be defined. The effectiveness of the current COVID-19 vaccines against prevailing variants of SARS-CoV-2 is reassuring. However, strict surveillance to identify new variants of concern is required in order to change our mind-set from a reactive to a more proactive and predictable approach.

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