An updated review on pathogenic coronaviruses (CoVs) amid the emergence of SARS-CoV-2 variants: A look into the repercussions and possible solutions.

SARS-CoV-2, responsible for COVID-19, shares 79% and 50% of its identity with SARS-CoV-1 and MERS-CoV, respectively. It uses the same main cell attachment and entry receptor as SARS-CoV-1, which is the ACE-2 receptor. However, key residues in the receptor-binding domain of its S-protein seem to give it a stronger affinity for the receptor and a better ability to hide from the host immune system. Like SARS-CoV-1 and MERS-CoV, cytokine storms in critically ill COVID-19 patients cause ARDS, neurological pathology, multiorgan failure, and increased death. Though many issues remain, the global research effort and lessons from SARS-CoV-1 and MERS-CoV are hopeful. The emergence of novel SARS-CoV-2 variants and subvariants raised serious concerns among the scientific community amid the emergence of other viral diseases like monkeypox and Marburg virus, which are major concerns for healthcare settings worldwide. Hence, an updated review on the comparative analysis of various coronaviruses (CoVs) has been developed, which highlights the evolution of CoVs and their repercussions.

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.

Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance.

Abatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35+ IL-10+ Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3+ conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-ß in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-135+ IL-10+ Bregs.