SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry

Abstract

Our review summarizes the evidence that COVID-19 can be complicated by SARS-CoV-2 infection of immune cells. This evidence is widespread and accumulating at an increasing rate. Research teams from around the world, studying primary and established cell cultures, animal models, and analyzing autopsy material from COVID-19 deceased patients, are seeing the same thing, namely that some immune cells are infected or capable of being infected with the virus. Human cells most vulnerable to infection include both professional phagocytes, such as monocytes, macrophages, and dendritic cells, as well as nonprofessional phagocytes, such as B-cells. Convincing evidence has accumulated to suggest that the virus can infect monocytes and macrophages, while data on infection of dendritic cells and B-cells are still scarce. Viral infection of immune cells can occur directly through cell receptors, but it can also be mediated or enhanced by antibodies through the Fc gamma receptors of phagocytic cells. Antibody-dependent enhancement (ADE) most likely occurs during the primary encounter with the pathogen through the first COVID-19 infection rather than during the second encounter, which is characteristic of ADE caused by other viruses. Highly fucosylated antibodies of vaccinees seems to be incapable of causing ADE, whereas afucosylated antibodies of persons with acute primary infection or convalescents are capable. SARS-CoV-2 entry into immune cells can lead to an abortive infection followed by host cell pyroptosis, and a massive inflammatory cascade. This scenario has the most experimental evidence. Other scenarios are also possible, for which the evidence base is not yet as extensive, namely productive infection of immune cells or trans-infection of other non-immune permissive cells. The chance of a latent infection cannot be ruled out either.

Cell-intrinsic and -extrinsic effects of SARS-CoV-2 RNA on pathogenesis: single-cell meta-analysis

“…We found a smaller number of viral positive cells in the human macrophage clusters compared with the animal models, which may be due to sample collection methodology and tissue types available for human patients. Consistent with other single-cell RNA-seq studies, viral RNA has been found in multiple immune cells, including myeloid cells with phagocytic activity (neutrophil, monocyte, and macrophage) and lymphocytes without phagocytic activity (T, B, and NK cells) ( 17 , 18 ). We also found viral genes in human epithelial cells, B cells, APOC1 + macrophages, and T cells but did not find any evidence of host/viral sDEGs in either APOC1 + macrophages or T cells.…”

Humoral Response to Dengue Virus Infections Potentiates Antibody-Dependent Enhancement of SARS-CoV-2

“…was not significatively demonstrated in COVID-19 vaccines [50]. Possibly, because highly fucosylated antibodies of vaccinees did not cause ADE, but fucosylated antibodies produced in acute primary infection or convalescents sera can induce it [39]. It is essential for vaccine development to balance between ADE and neutralizing antibodies.…”

“…Macrophages can phagocyte the virus, but it does not result in productive infection. However, SARS-CoV-2 entry into immune cells leads to an abortive infection followed by host cell pyroptosis, the release of proinflammatory cytokines, and the activation of inflammasomes [39,40]. Alternatively, infected monocytes can act like trojan horses, spreading the virus to different tissues.…”

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

“…To our knowledge, one of the ways SARS-CoV-2 invades human cells is through a process known as endocytosis. This intricate mechanism involves the virus binding to receptors on the surface of host cells, such as the ACE2 receptor, and then being engulfed by the cell, thus allowing it to evade the body’s immune system and replicate within the host ( Matveeva et al, 2022 ). However, in the ongoing battle against COVID-19, neutralizing antibody (nAb) therapy has emerged as a promising strategy to combat the virus.…”