Immunomodulatory Drugs in the Management of SARS-CoV-2

Abstract

With the onset of the global pandemic in 2020 of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), there has been increasing research activity around certain disease-modifying drugs that are used for the management of inflammatory disorders such as rheumatoid arthritis, spondyloarthrosis, psoriatic arthritis, systemic lupus erythematosus, and inflammatory bowel disease for managing coronavirus symptoms. In the conditions mentioned, many people are on long-term treatment with agents including hydroxychloroquine, tumor necrosis factor alpha (TNFα) inhibitor drugs, other biologic agents such as monoclonal antibodies to IL-6 and Janus kinase inhibitors including baricitinib and tofacitinib, which are used to control inflammatory responses in their respective auto-immune condition. There is emerging data that immunomodulatory drugs could be protective at reducing certain features of SARS-CoV-2 and improving recovery. In addition, it is important to understand if subjects being treated with the immunomodulatory agents described have a less severe SARS-CoV-2 infection, as they are deemed some protection from their immunomodulatory treatment, or if they develop infections similar to non-immunocompromised patients. There is a huge unmet clinical need to advise patients responsibly about whether they should remain on their immunomodulatory treatment or not in light of Covid-19 infection. In this article we will discuss potential treatment options for SARS-CoV-2 using immunomodulatory drugs and at what stage of the condition they may be beneficial. Viable treatment options during the global coronavirus pandemic are a much-needed and an intensely active area of research.

Keywords: SARS-CoV-2; biologics; cytokines; hyperinflammation; immunomodulators.

Figure 1

Potential therapeutic approaches for the management of SARS-CoV-2 infection. Mechanisms of cell injury and damage are shown in peach boxes. Green boxes show potential therapeutic targets and immune responses to modify and alleviate infection.

Figure 2

Changes in patient's clinical, radiographic and biochemical parameters on treatment with tocilizumab. (A) Chest radiograph on admission. This demonstrates minor bi-basal opacity more pronounced on the right. (B) Chest radiograph on day 3. This demonstrates patchy areas of consolidation within the lung peripheries bilaterally with retrocardiac left lower zone opacification with air bronchograms. Graphs showing changes in the maximal daily values of parameters for patient's hospital admission for temperature (C), respiratory rate (D) oxygen requirement (E), serum C reactive protein levels (F), ferritin levels (G), and D-dimers (H). Arrows indicate Day 7 when tocilizumab was given.