Pathological effects of SARS-CoV-2 on hematological and immunological cells: Alterations in count, morphology, and function

Abstract

The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 outbreak, spread rapidly and infected more than 140 million people with more than three million victims worldwide. The SARS-CoV-2 causes destructive changes in the immunological and hematological system of the host. These alterations appear to play a critical role in disease pathology and the emerging of clinical manifestations. In this review, we aimed to discuss the effect of COVID-19 on the count, function and morphology of immune and blood cells and the role of these changes in the pathophysiology of the disease. Knowledge of these changes may help with better management and treatment of COVID-19 patients.

Keywords: Blood platelets; Erythrocytes; Granulocytes; Immunity; Monocytes; SARS-COV-2.

Fig. 1

Role of neutrophils in hypercoagulable state of COVID-19 patients. After the entrance of the SARS-CoV2 virus into the respiratory system, it enters the epithelial cells through ACE2 and causes some damages. This virus travels to the alveoli of the lungs and innate immune cells are recruited. Monocytes activate by identifying PAMPs and DAMPs and neutrophils are recruited and cytokine storm occurs by producing some inflammatory cytokines such as IL-6, IL-1b, TNF-α. Therefore, infiltration of neutrophils occurs, which produce NETs. The NETosis process has some connections with macrophages in the tissue. NETs are composed of MPO, NE, H3, H4, LL37, etc. LL37 activates the p2x7r channel on macrophages and then the efflux of K⁺ ions occur. Hence, NLRP3 inflammasome activates and macrophages produce some cytokines such as IL-1b and IL-18 that can help neutrophils to produce more NETs. On the other hand, the neutrophils that produce NETs can link to platelets in the blood through PSGL1 and p-selectin on the platelets and activate them. These activated platelets release poly p and PDI. PDI, as an enzyme, causes the release of TF micro- vesicles from activated monocytes. Not only this TF activates the extrinsic pathway of coagulation but also adheres to the NETs. VWF adheres to these NETs too, and they can form a scaffold for thrombosis happening. Also, the intrinsic pathway can be activated by activating factor XII on this scaffold. NE extraction of neutrophils inhibits some inhibitory factors of the coagulation system such as protein C, thrombomodulin, and TFPI. Finally, all of the above cause thrombosis in the veins or arteries of COVID19 patients.

Fig. 2

Interaction between Monocytes-Platelets-T cells in COVID-19 patients. In COVID-19 patients, the relationship between platelets, monocytes, and T cells exacerbates the cytokine storm, enhances coagulopathies, and diminished the antiviral response of T lymphocytes. As shown figure, the monocyte-platelet interaction through Mac-1/αIIbβ3 and PSGL-1/CD62P leads to the release of TF, FV, and FXIII from platelets. On the other hand, activated platelets can affect the T cell responses by altering some CD4+ T cell functions and Antigen presentation to CD8+ T cells. Moreover, excessive secretion of GM-CSF by T cells exacerbates cytokine release and TF production by monocytes and differentiates them toward M1 pro-inflammatory macrophages. A decrease in the HLA-DR expression on monocytes results in more attenuation of the T cell response due to a decrease in antigen presentation.