Functionality of immune cells in COVID-19 infection: development of cell-based therapeutics.

Introduction: In late December 2019, a sudden severe respiratory illness of unknown origin was reported in China. In early January 2020, the cause of COVID-19 infection was announced a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Examination of the SARS-CoV-2 genome sequence revealed a close resemblance to the previously reported SARS-CoV and coronavirus Middle East respiratory syndrome (MERS-CoV). However, initial testing of drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. One of the key strategies to fight the virus is to look at how the immune system works against the virus, which has led to a better understanding of the disease and the development of new therapies and vaccine designs. Methods: This review discussed the innate and acquired immune system responses and how immune cells function against the virus to shed light on the human body's defense strategies. Results: Although immune responses have been revealed critical to eradicating infections caused by coronaviruses, dysregulated immune responses can lead to immune pathologies thoroughly investigated. Also, the benefit of mesenchymal stem cells, NK cells, Treg cells, specific T cells, and platelet lysates have been submitted as promising solutions to prevent the effects of infection in patients with COVID-19. Conclusion: It has been concluded that none of the above has undoubtedly been approved for the treatment or prevention of COVID-19, but clinical trials are underway better to understand the efficacy and safety of these cellular therapies.

Development of an mRNA-LNP Vaccine against SARS-CoV-2: Evaluation of Immune Response in Mouse and Rhesus Macaque.

Among the vaccines have been developed thus far against SARS-CoV-2, the mRNA-based ones have demonstrated more promising results regarding both safety and efficacy. Two remarkable features of the mRNA vaccines introduced by the Pfizer/BioNTech and Moderna companies are the use of (N1-methyl-pseudouridine-) modified mRNA and the microfluidics-based production of lipid nanoparticles (LNPs) as the carrier. In the present study, except Anti-Reverse Cap Analog (ARCA), no other nucleoside analogs were employed to synthesize Spike-encoding mRNA using the in vitro transcription (IVT) method. Furthermore, LNPs were prepared via the ethanol injection method commonly used for liposome formation as an alternative for microfluidics-based approaches. The produced mRNA-LNP vaccine was evaluated for nanoparticles characteristics, encapsulation and transfection efficiencies, in vitro cytotoxicity as well as stability and storability. The safety of vaccine was assessed in Balb/c mice injected with mRNA-LNPs containing 10 µg of spike-encoding mRNA. Eventually, the vaccine efficacy in inducing an immune response against SARS-CoV-2 was studied in Balb/c and C57BL/6 mice (received either 1 or 10 µg of mRNA) as well as in rhesus macaque monkeys (infused with mRNA-LNPs containing 100 µg of mRNA). The ELISA and virus neutralizing test (VNT) results showed a significant augmentation in the level of neutralizing antibodies against SARS-CoV-2. Moreover, the ELISA assay showed virus-specific IFN-γ secretion in immunized mice as a marker of TH1 cell-based immune response, whereas favorably no change in the production of IL-4 was detected.

The risk of pancreatic adenocarcinoma following SARS-CoV family infection.

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.

Plasma exchange followed by convalescent plasma transfusion in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerged pandemic disease with no specific treatment. One of the potential treatments in newly found infectious disease is plasma exchange (PE) with convalescent plasma transfusion (CPT). This case series aimed to evaluate the primary PE and CPT in five Iranian COVID-19 patients. METHODS: Five patients with confirmed COVID-19 who had acute respiratory distress syndrome and were supported by mechanical ventilation were treated with two consecutive PE containing fresh frozen plasma (FFP) of healthy donors and 0.9 % saline solution containing 5 % human albumin. Thereafter, CPT was performed just like PE, except that the FFP in this step was substituted with convalescent ABO-matched plasma. Clinical and laboratory factors were evaluated before and after treatments. RESULTS: Three to Four patients showed lower body temperature and improved oxygen saturation as well as reduced laboratory factors such as c-reactive protein, lactate dehydrogenase, creatine phosphokinase (total and myocardial isoform), aspartate aminotransferase, blood urea nitrogen, bilirubin (total and direct), D-dimer, interleukin-6, and CD4+/CD8 + T cells ratio initially after PE and continued to improve so that they were discharged. One patient due to secondary hemophagocytic lymphohistiocytosis and extensive lung fungal infection was expired. DISCUSSION: Overall, the PE followed by CPT was beneficial in reducing acute inflammation led to a considerable improvement in patients' clinical features. It seems that PE along with CPT could provide clearance of pro-inflammatory mediators as well as the positive effects of CPT. Controlled studies are required to confirm the effect of PE/CPT compared with other therapeutic approaches.