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.

Autophagy, the molecular machinery of self-eating, plays a dual role of a tumor promoter and tumor suppressor. This mechanism affects different clinical responses in cancer cells. Autophagy is targeted for treating patients resistant to chemotherapy or radiation. Limited reports investigate the significance of autophagy in cancer therapy, the regulation of hematopoietic and leukemic stem cells and leukemia formation. In the current review, the role of autophagy is discussed in various stages of hematopoiesis including quiescence, self-renewal, and differentiation. K E Y W O R D S autophagy, hematopoiesis, leukemia 1 | INTRODUCTION Autophagy plays a crucial role in removing damaged organelles and protein aggregates from the cytoplasm through lysosomal pathways. To date, autophagy includes three main types: Macroautophagy, in which cytoplasmic components are engulfed by autophagosome, whereas both microautophagy and chaperone-mediated autophagy are characterized by having proteins that directly fuse to the lysosomes (Chen & White, 2011; Levine & Kroemer, 2008).Autophagy is upregulated by inhibiting mammalian targets of rapamycin (mTOR) when cells require nutrients and energy production (Tanaka et al., 2012). Autophagy has been originally identified in yeasts as a group of autophagy-related (Atg) genes and is a wellconserved evolutionary pathway in eukaryotes that has been shown to be implicated in degradation and recycling. These proteins are essential for membrane isolation and the formation of autophagosome ( Figure 1). In conditions of poor nutrients, increased AMP/ATP ratio activates AMPK, which inhibits mTORC1 and induces autophagy. In this setting, uncoordinated 51-like kinase 1 (ULK1), binds to dephosphorylated ATG13, which is normally hyperphosphorylated by mTOR and other kinases, ATG101 and FIP200, forming a tetrameric complex called ATG1/ULK1 complex. Upon the activation of ULK1, Beclin1 is phosphorylated and forms the class III PI3K complex containing ATG14, VPS15, Ambra1, and VPS34. The formation of these two complexes is essential for induction of autophagy nucleation. In fact, phosphatidylinositol 3-phosphate [PI(3)P] is generated by the PI3K complex at the nucleation site of a doublemembraned structure, called phagophore or isolated membrane, F I G U R E 1 Autophagic machinery in leukemia. The PI3K/AKT/mTORC1 pathway plays an important role in the regulation of HSC quiescence and the incidence of leukemia. Incorrect initiation of this process can lead to the inhibition of autophagy. Many factors, such as RTKs stimulate PI3K activity and form PIP3 from PIP2. PIP3 activates PDK and AKT. Activated AKT inhibits the FOXO activity in RTKs expression. In addition, AKT stimulates phosphorylation of TSC2 and leads to inhibition of the TSC1/TSC2 complex function. The containment of the TSC1/TSC2 complex causes Rheb to accumulate in the form of Rheb-GTP, which stimulates and activates mTORC1. The mTORC1 targets three major factors in cell translation including p70s6k, 4E-BP1, and Eif4e. P70S6K controls the PI3K...

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.