Immune Profiling of COVID-19 in Correlation with SARS and MERS

Abstract

Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen.

Keywords: COVID-19; MERS-CoV; SARS-CoV; SARS-CoV-2; chemokines; cytokines.

Figure 1

Innate and adaptive immune cells involved in SARS-CoV-2 infection, as well as the different chemokines and cytokines released and their inhibitors. SARS-CoV-2 binds ACE2 receptor on epithelial cells (ECs) and on macrophages (MΦ) of the alveoli. This triggers the release of cytokines and chemokines that attract more immune cells to the injured lung. Upon infection, activated DCs migrate to the lymph node (LN), where they activate T- and B-lymphocytes, which will further release pro-inflammatory mediators that exacerbate the infection. Several drugs currently used on patients or being tested in clinical trials target the various chemokines and cytokines responsible for the cytokine storm in COVID-19, including IL-6 inhibitors, INF, IL-1β inhibitors, JAK inhibitors, and IL-17 antibodies.