The immune system as a target for therapy of SARS-CoV-2: A systematic review of the current immunotherapies for COVID-19

Abstract

Aims: The immune response is essential for the control and resolution of viral infections. Following the outbreak of novel coronavirus disease (COVID-19), several immunotherapies were applied to modulate the immune responses of the affected patients. In this review, we aimed to describe the role of the immune system in response to COVID-19. We also provide a systematic review to collate and describe all published reports of the using immunotherapies, including convalescent plasma therapy, monoclonal antibodies, cytokine therapy, mesenchymal stem cell therapy, and intravenous immunoglobulin and their important outcomes in COVID-19 patients.

Material and methods: A thorough search strategy was applied to identify published research trials in PubMed, Scopus, Medline, and EMBASE from Dec 1, 2019, to May 4, 2020, for studies reporting clinical outcomes of COVID-19 patients treated with immunotherapies along with other standard cares.

Key findings: From an initial screen of 80 identified studies, 24 studies provided clinical outcome data on the use of immunotherapies for the treatment of COVID-19 patients, including convalescent plasma therapy (33 patients), monoclonal antibodies (55 patients), interferon (31 patients), mesenchymal stem cell therapy (8 patient), and immunoglobulin (63 patients). Except for nine severe patients who died after treatment, most patients were recovered from COVID-19 with improved clinical symptoms and laboratory assessment.

Significance: Based on the available evidence, it seems that treatment with immunotherapy along with other standard cares could be an effective and safe approach to modulate the immune system and improvement of clinical outcomes.

Keywords: COVID-19; Coronavirus; Immune system; Immunotherapy; SARS-COV-2.

Graphical abstract

Fig. 1

Structural proteins of SARS-CoV-2: Sprotein (spike glycoprotein trimmer), M protein (a type III transmembrane glycoprotein), E protein (located among the S proteins in the virus envelope), N proteins (nucleocapsid), HE (hemagglutinin-esterase) dimer (exists in some CoVs).

Fig. 2

PRISMA flowchart.

Fig. 3

The mechanism of the innate and acquired immune response following by attaching the virus to the ACE2 receptor and the current immunotherapies for treatment the COVID-19 patients. Viral interactions with the innate and acquired immune system play a central role in determining the outcome of infection. Local inflammation formed in the site of the infection, triggers immune cells to limit viral spread within the host during the early phases of the disease via producing cytokines and other chemokines. Current immunotherapies including monoclonal antibodies, convalescent plasma therapy, IVIg, mesenchymal stem cell therapy in COVID-19 patients are also shown. Up to now, most clinical trials have been performed on Tocilizumab and convalescent plasma therapy with inspiring outcomes. Depicted monoclonal antibodies are currently being evaluated by registered clinical trials. ACE2R: angiotensin-converting enzyme 2 receptor; IL: interleukin; MCP1: monocyte chemoattractant protein1; IP10: interferon-inducible protein 10; IF: interferon; PD-1: programmed cell death protein 1; MIP1: macrophage inflammatory proteins1; TNF: tumor necrosis factor; PMN: polymorphonuclear granulocyte; NK: natural killer; Treg cell: regulatory T cell; CSF: colony stimulating factor; IVIg: intravenous immunoglobulin.