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.

Recent emergence of SARS-CoV-2 and associated COVID-19 pandemic have posed a great challenge for the scientific community. In this study, we performed bioinformatic analyses on SARS-CoV-2 protein sequences, trying to unravel potential molecular similarities between this newly emerged pathogen with non-coronavirus ssRNA viruses. Comparing the proteins of SARS-CoV-2 with non-coronavirus positive and negative strand ssRNA viruses revealed multiple sequence similarities between SARS-CoV-2 and non-coronaviruses, including similarities between RNA-dependent RNA-polymerases and helicases (two highly-conserved proteins). We also observed similarities between SARS-CoV-2 surface (i.e. spike) protein with paramyxovirus fusion proteins. This similarity was restricted to a segment of spike protein S2 subunit which is involved in cell fusion. We next analyzed spike proteins from SARS-CoV-2 “variants of concern” (VOCs) and “variants of interests” (VOIs) and found that some of these variants show considerably higher spike-fusion similarity with paramyxoviruses. The ‘spike-fusion’ similarity was also observed for some pathogenic coronaviruses other than SARS-CoV-2. Epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that several B cell epitopes as well as T cell and MHC binding epitopes map within the spike-fusion similarity region. These data indicate that there might be a degree of convergent evolution between SARS-CoV-2 and paramyxovirus surface proteins which could be of pathogenic and immunological importance.

Recent emergence of SARS-CoV2 and associated COVID-19 pandemic has posed a great challenge for the scientific community. Understanding various aspects of SARS-CoV2 biology, virulence and pathogenesis as well as determinants of immune response have become a global research priority. In this study, we performed bioinformatic analyses on SAR-CoV2 protein sequences, trying to unravel biologically important similarities between this newly emerged virus with other RNA viruses. Comparing the proteome of SARS-CoV2 with major positive and negative strand ssRNA viruses showed significant homologies between SARS-CoV2 spike protein with various pathogenic paramyxovirus fusion proteins. The 'spike-fusion' homology was not limited to SARS-CoV2 and it existed for some other pathogenic betacoronaviruses; nonetheless, SARS-CoV2 spike-fusion homology was orders of magnitude stronger than for other coronaviruses. Moreover, this homology did not seem to be a consequence of general ssRNA virus phylogenetic relations. We then explored potential immunological significance of this spike-fusion homology. Spike epitope analysis using experimentally verified epitopes deposited in Immune Epitope Database (IEDB), revealed that the majority of T cell epitopes as well as B cell and MHC binding epitopes map within the spike-fusion homology region. Overall, our data indicate that there might be a relation between SARS-CoV2 and paramyxoviruses at the level of their surface proteins and this relation might be of crucial immunological importance.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Myelin-autoreactive T cells have been implicated in the initiation of an inflammatory cascade. Dendritic cells (DC) are key modulators of this immuno-pathological cascade. The interaction between immune complexes (IC) and FcγRs results in activation of the immune system and induction of host inflammatory responses. Otherwise, monocytes differentiate into DCs after ligation of their FcγRs to IgG. We investigated circulating immune complexes levels (CIC) and differentiation of monocytes onto immature dendritic cell (iDC) via FcγR by Plate-bound human IgG in MS patients compared to healthy individuals. Our results showed that the concentration of CIC in patients with MS was significantly higher than healthy controls. Human IgG alone differentiate monocytes into DCs with a phenotype, including up-regulation of CD1b, CD86 and down- regulation of CD14. Also, the ability of LPS/MBP matured DCs in activation and cytokine production of autologous T cells was evaluated by MLR assay and ELISA. The level of IL-17 was significantly higher in MS patients when IgG derived DCs cocultured with T cells. Also, a correlation between IL-17 levels and circulating immune complexes level was observed in MS patients. Therefore, activation of FcγR on monocytes triggers differentiation into specialized iDC with the capacity to induce auto-reactive T cells that may contribute to the pathogenesis of MS.

Unraveling molecular interactions between viral proteins and host cells is key to understanding the pathogenesis of viral diseases. We hypothesized that potential sequence and structural similarities between SARS-CoV2 proteins and proteins of infected cells might influence host cell biology and antiviral defense. Comparing the proteins of SARS-CoV-2 with human and mammalian proteins revealed sequence and structural similarities between viral helicase with human UPF1. The latter is a protein that is involved in nonsense mediated RNA decay (NMD), an mRNA surveillance pathway which also acts as a cellular defense mechanism against viruses. Protein sequence similarities were also observed between viral nsp3 and human Poly ADP-ribose polymerase (PARP) family of proteins. Gene set enrichment analysis on transcriptomic data derived from SARS-CoV-2 positive samples illustrated the enrichment of genes belonging to the NMD pathway compared with control samples. Moreover, comparing transcriptomic data from SARS-CoV2-infected samples with transcriptomic data derived from UPF1 knockout cells demonstrated a significant overlap between datasets. These findings suggest that helicase/UPF1 sequence and structural similarity might have the ability to interfere with the NMD pathway with pathogenic and immunological implications.