Regulatory T cell dysfunction is partially responsible for the dysfunction of the SARS-CoV-2 inflammatory response, one of these dysfunctions being the cytokine storm. Therefore, immunotherapy to treat CD8+ T cells may help to control inflammation in lung tissue. 

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Antivirals, glucocorticoids, and immunoglobulin treatments have not proven to significantly improve the clinical outcome of COVID-19, therefore targeting specific aspects of the immune response to SARS-CoV-2 may be more effective. Enhancing lymphocytes with strategies such as NK cell-based therapy; immunomodulators; and convalescent plasma therapy, and inhibiting inflammation using strategies such as mesenchymal stem cell-based therapy; regulatory T cell-based therapy; blood purification; blocking IL-6 signalling; and Janus kinase inhibitors should be explored. 

Potential Immunotherapeutic Strategies for COVID-19

Yang, Li, et al. “COVID-19: Immunopathogenesis and Immunotherapeutics.” Signal Transduction and Targeted Therapy, vol. 5, no. 1, 2020, doi:10.1038/s41392-020-00243-2.

https://www.nature.com/articles/s41392-020-00243-2

COVID-19: Immunopathogenesis and Immunotherapeutics

Because NK cell-based therapy has shown to be effective against tumors by activating an antigen-dependent immune response, it has been approved as a treatment for COVID-19 in China, bolstering antiviral defenses and enhancing the immune response.

NK Cell-based Therapy 

Antibodies in convalescent plasma may inhibit viremia, making it an efficient treatment. However, this treatment has shown to be less effective in the late stages of the disease and may be difficult to obtain because large amounts of plasma are required and transfusions are typically done in a hospital setting. Though there is not strong evidence that this treatment causes severe adverse events, the patient may experience mild fever, allergic reactions, bronchospasms, transfusion-related acute lung injury, and circulatory overload in patients with cardiorespiratory disorders.

Convalescent Plasma Therapy 


MSCs have limitless self-renewal and multipotency that can be used to safely and efficiently reduce the harm of the immune response to SARS-CoV-2 and treat SARS-CoV-2-induced pneumonia. They can do this by defending against the cytokine storm, repairing pulmonary epithelial cell damage, and enhancing alveolar fluid clearance. Since this treatment has been proven to be effective in both preclinical and clinical trials, it has been cleared to be employed in China.

Mesenchymal Stem Cell-based Therapy

Regulatory T Cell-based Therapy 

China has approved blood purification treatment–the process of removing toxins and wastes from the blood–for severe and critical COVID-19 patients, as it has been proven to prevent cytokine storms and suppress inflammation.

Blood Purification 

JAK pathway inhibitors may be able to reduce the elevated cytokine levels in COVID-19 patients, lessening the consequences of inflammation. Additionally, dihydroorotate dehydrogenase inhibitors have been demonstrated to alleviate cytokine storms and inhibit viral replication in animal trials.

Anti-inflammatory Agents 

Immunomodulators, chemicals that affect immune system function, have been proven effective against other viral infections and can be used to combat SARS-CoV-2 by both stimulating the innate antiviral response and performing immune regulatory functions.

Immunomodulators

The IL-1 family of cytokines regulates production of IL-6, and thus may serve as a potential immunomodulatory therapeutic target. Moreover, high levels of IL-1β and its endogenous antagonist, IL-1 receptor antagonist (IL-1 Ra) are associated with COVID-19 onset. Several existing drugs that block IL-1 signaling such as Anakinra and Canakinumab have been proposed as drug options for SARS-CoV-2 infection.

Blocking IL-1 Signaling

JAK-STAT receptors regulate the production of several cytokines that are involved in the cytokine storm response associated with COVID-19, including IL-6, IL-1, etc. Moreover, these receptors control the differentiation of CD4 cells to the different T helpers, such as Th1, Th2, and Th17.

Blocking JAK-STAT Signaling

The IL-6 receptor is a proposed target for treatment because IL-6 is responsible for inducing the cytokine storm. Tocilizumab is an anti-IL-6 receptor antibody used to treat certain forms of arthritis. In China, it has been demonstrated to reduce fever and improve respiratory function in patients with severe COVID-19. Sarilumab is another anti-IL-6 receptor antibody treatment option that binds and blocks IL-6 recptors.

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