The immunology of COVID-19: is immune modulation an option for treatment?

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for over 500 thousand deaths in 216 countries across the world and is affecting over 10 million people. The absence of FDA approved drugs against the new SARS-CoV-2 virus has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and the SARS-CoV-2 virus to provide insight into the pathogenetic mechanism of the virus and to support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, rst of all, in its healthy state. We then demonstrate how the entry of the SARS-CoV-2 virus into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. We have completed a comparative analysis of our model and other previously generated cell type models and highlight 48 pathways and over 800 reactions hijacked by the virus for its replication and survival. We designed a new tool which predicts 15 unique reactions as drug targets from our models (the integrated human macrophage, human airway epithelial cells and the SARS-CoV2 virus) and provide a platform for future studies on viral entry inhibition and drug optimisation strategies.

Obesity and COVID-19: A Perspective from the European Association for the Study of Obesity on Immunological Perturbations, Therapeutic Challenges, and Opportunities in Obesity

“…This approach takes advantage of existing detailed information on human pharmacology and toxicology to enable rapid clinical trials and regulatory review. Immune-Modulating Drugs Given the importance of immune imbalance in the pathogenesis of SARS-CoV-2 infection, several immune-modulating drugs that regulate different aspects of inflammation are currently being tested for their efficacy in the treatment of severe COVID-19 [37,75]. Since hyperinflammation is an important determinant of tissue damage, organ failure, and disease outcome in COVID-19, immunosuppression might reduce mortality in patients with severe symptoms [43,51].…”

Delayed Presentation of Acute Generalized Exanthematous Pustulosis Following Treatment with Cefepime in a Patient with COVID-19 without the Use of Hydroxychloroquine

“…In COVID-19, the antiviral immune response is crucial to eliminating the invading virus, and researchers are finding that pro-inflammatory subsets of T cells (including Th17 and other CD4+ T cells, as well as CD8+ T cells) are likely responsible for the severe immune-related injury to various organ systems [ 10 ]. It is thought that a robust and persistent immune response may lead to an overproduction of inflammatory cytokines, causing damage to host tissues [ 10 ].…”

C-C Chemokine Receptor Type 5 Links COVID-19, Rheumatoid Arthritis, and Hydroxychloroquine

“…Due to the immune dysregulation as well as the use of immune-modulating treatments, patients with rheumatic diseases were considered among the fragile subpopulations that might suffer from the more aggressive form of COVID19 [3][4][5]. Interestingly, a group of disease-modifying anti-rheumatic drugs (DMARDS), including HCQ and IL6 inhibitors such as tocilizumab, was also proposed as a possible therapeutic option to treat COVID-19 patients [18]. However, the mechanisms through which those agents produce their effect is not fully understood.…”