Submitted by: Lillian Wu, SRT, Conestoga College

In current world events, it is impossible to find someone who hasn’t been affected, either themselves or through a personal connection, by COVID-19. This infectious respiratory disease caused by a specific strain of coronavirus first made an appearance in Wu Han, China in early December of 2019 (Alijotas-Reig et al., 2020). Since then, it has spread rapidly across the globe, affecting four million people and causing over 280 000 deaths as of May of 2020 and these numbers increase daily (Jing, Vunnam, Yang, Karevoll & Vunnam, 2020). In most patients, the symptoms are similar to a mild flu, but in 15-20% of patients the symptoms are more severe and can even lead to acute respiratory distress syndrome (ARDS) (Diamanti, Rosado, Pioli, Sesti & Laganà, 2020). These severe consequences can be traced to the uncontrolled immune response that COVID-19 can cause, also known as a “cytokine storm” (Diamanti et al., 2020, p. 2). Lots of different trial treatment options have been attempted such as anti-virals and anti-malarials, and vaccine research and development (Jing et al., 2020). There are many pros and cons of each, but in the frenzy to help relieve more serious symptoms while a vaccine is being developed, researchers have turned to anti-inflammatories as a method of treatment (Saghazadeh & Rezaei, 2020).

There are a lot of similarities between people infected with COVID-19 and people who suffer from hyper-inflammatory diseases such as hemophagocytic syndrome (HPS), macrophage activation syndrome (MAS), Still’s disease, and systemic lupus (Alijotas-Reig et al., 2020). Hemophagocytic syndrome leads to uncontrollable activation of cytotoxic T lymphocytes, natural killer cells and macrophages normally used by the body to defend themselves from diseases, but once overproduced, results in hypercytokinemia and can cause multiple organ failure leading to death (Alijotas-Reig et al., 2020). Similar to HPS, COVID-19 causes a high release of pro-inflammatory cytokines such as IL-1, IL-2, IL-6 and TNF-a (Alijotas-Reig et al., 2020). Therefore, in theory, anti-inflammatory drugs used to suppress them should work to reduce severe symptoms (Alijotas-Reig et al., 2020).

In a trial done on 21 patients with COVID-19, Tocilizumab, which is normally used to treat patients with cytokine release syndrome and rheumatoid arthritis, has shown positive results in clinical symptoms and peripheral oxygen saturation (Saghazadeh & Rezaei, 2020). When used on COVID-19 patients with severe symptoms and high IL-6 levels, Tocilizumab has erased lung lesion opacity, lowered C-reactive proteins, and normalized lymphocyte counts (Alijotas-Reig et al., 2020). Other versions of IL-6 blockers, such as anti-IL-1 and interleukin-2 inhibitors have also been researched with similar results (Alijotas-Reig et al., 2020). Janus kinase pathway (JKP) inhibitors have also been tested and have the benefit of affecting both inflammation and cellular viral entry, making it an interesting type of drug to research in its use as an acute respiratory disease treatment (Alijotas-Reig et al., 2020). In a trial on mice, ruxolitinib, a common JKP inhibitor, was used to treat HPS and results showed a rapid decrease in serum IL-6 and TNF-a levels leading to encouraging trials using ruxolitinib to treat COVID-19 as well (Alijotas-Reig et al., 2020). Although the trials are only in their preliminary rounds, the results are very promising (Alijotas-Reig et al., 2020).

Bulut and Gursel (2020) have taken a step further into the idea and looked into mesenchymal stem cell derived extracellular vesicles (MSC EVs) as an immunosuppressive agent (p. 278). MSC EVs are often used in the treatment of multiple autoimmune diseases such as type 1 diabetes, inflammatory bowel disease and rheumatoid arthritis, by inhibiting T cell proliferation (Bulut & Gursel, 2020). The authors concluded that MSC EVs could be a safe and viable way to treat COVID-19 driven pneumonia and lung pathology (Bulut & Gursel, 2020).  More research has to be done in order to reveal the mechanism of immunomodulation with proteomics, lipidomics and RNA-sequencing, but the idea of MSC EVs as a viable and safe way of not only helping patients who suffer from autoimmune diseases, but also as a method of treatment for COVID-19 that is potentially ground-breaking (Bulut & Gursel, 2020).

Immunosuppressive drugs are not a cure for COVID-19 but can help a lot of patients who suffer from the extreme symptoms that are linked to sustained IL-6 and IL-1 elevation (Alijotas-Reig et al., 2020). Although there is nothing that is set in stone when talking about a complete treatment regime for COVID-19, there are many scientists working hard every single day to get humanity closer to eradicating this devastating pandemic. In the meantime, proper social distancing practices, masking, and good personal hygiene is still the best way reduce the chances of contracting COVID-19 (Jing et al., 2020).

References

Alijotas-Reig, J., Esteve-Valverde, E., Belizna, C., Selva-O’Callaghan, A., Pardos-Gea, J., Quintana, A., Mekinian, A., Anunciacion-Llunell, A., & Miró-Mur, F. (2020).
Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review. Autoimmunity Reviews, 19 (7), 1-9. https://doi.org/10.1016/j.autrev.2020.102569

Bulut, O., & Gürsel, I. (2020).
Mesenchymal stem cell derived extracellular vesicles: promising immunomodulators against autoimmune, autoinflammatory disorders and SARS-CoV-2 infection. Turkish Journal of Biology, 44 (3), 273-282. doi:10.3906/biy-2002-79.

Diamanti, A.P., Rosado, M.M., Pioli, C., Sesti, G., & Laganà, B. (2020).
Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity. International Journal of Molecular Science, 21 (9), 1-18. https://doi.org/10.3390/ijms21093330

Jing, R., Vunnam, R.R., Yang, Y., Karevoll, A., & Vunnam, S.R. (2020).
Current Status of Treatment Options, Clinical Trials, and Vaccine Development for SARS-CoV-2 Infection. Journal of Pure and Applied Microbiology, 14 (1), 733-740. https://doi.org/10.22207/JPAM.14.SPL1.10

Pious, N., & Ingole, S.D. (2020).
Pharmacological Treatment Options Which Can Be Considered for COVID-19. Society for Biomaterials & Artificial Organs, 34 (S2), 34-37. http://www.sbaoi.org/tibao

Saghazadeh, A., & Rezaei, N. (2020).
Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: Anti-antibodies, immunoglobulins, and corticosteroids. International Immunopharmacology. 84. https://doi.org/10.1016/j.intimp.2020.106560

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