COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs

Abdurrahman Tufan, Aslihan Avanoğlu Güler, Marco Matucci-Cerinic, Abdurrahman Tufan, Aslihan Avanoğlu Güler, Marco Matucci-Cerinic

Abstract

In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

Keywords: COVID-19; cytokine storm; inflammation; rheumatology; treatment; antiinflammatory.

Conflict of interest statement

CONFLICT OF INTEREST:

The authors declare no conflict of interest related to this paper.

This work is licensed under a Creative Commons Attribution 4.0 International License.

Figures

Figure 1
Figure 1
The schematic image of coronavirus (CoV). CoVs, enveloped virus, possess nonsegmented, positive (+) ssRNA genome with structural proteins: Spike (S) glycoprotein, membrane (M) protein, nucleocapsid (N) protein, and envelope (E) protein. SARS-CoV-2 S protein attaches to angiotensin-converting enzyme 2 (ACE2) receptor on the host cell to entry. After the attachment, host endosomal proteases mediate the virus membrane-endosome fusion for the release of the viral genome. Chloroquine (CQ) and hydroxycloroquine (HCQ) block the virus-receptor binding and virus-endosome fusion. Besides CQ, HCQ, and intravenous immunoglobulin (IVIg) inhibit the production of cytokines in macrophages and the antigen presentation in dendritic cells. In COVID-19, the count of neutrophils and leukosytes increase whereas the total count of lymphocytes CD4+ T cells, CD+8 T cells, regulatory T (T reg) cells, memory T cells, natural killer cells, and B cells decrease. Another beneficial effect of CQ and HCQ is increasing the activity of Treg. The aberrant proinflammatory cytokine production is observed in COVID-19. Several immunomodulatory therapies including interleukin (IL)-6 antagonists, granulocyte colony-stimulating factor (GM-CSF) inhibitor, IL-1 antagonists, IL-17 antagonists, and antitumor necrosis factor (TNF) agents might be used for this cytokine storm to resolve and limit the further inflammation and tissue damage (The yellow arrow indicates a decrease in the number of cells; the blue arrow indicates and increase in the number of cells).

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