Menstrual Blood-Derived Mesenchymal Stem Cell Therapy for Severe COVID-19 Patients.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), was declared a global pandemic in March 2020 and resulted in more than 6 million deaths worldwide to date. Although several vaccines were produced against COVID-19 and many therapeutic protocols were developed for the management of this respiratory infection, COVID-19 pandemic has still remained an unresolved problem with the emergence of new variants of SARS-CoV-2, especially vaccine-resistant variants. Probably, end of the COVID-19 needs effective and certain treatments which were undiscovered to date. According to immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) have been considered a therapeutic approach to suppressing cytokine storm caused by SARS-CoV-2 and the treatmet of severe COVID-19. Following intravenous (IV) infusion of MSCs, cells entrap in the lung, guard alveolar epithelial cells, suppress pulmonary fibrosis and improve lung dysfunction. The human menstrual blood-derived stem cells (hMenSCs) as a novel source of MSCs are collected by noninvasive, painless, and easy way without ethical issues. MenScs are an abundant and cheap source with a high proliferation rate and differentiation ability into multiple cell lineages. Regarding immunomodulatory and anti-inflammatory properties, regenerative ability and low immunogenicity, these cells exhibit great potential in the treatment of various diseases. Some clinical trial studies have begun using MenSCs to treat severe COVID-19. According to these trials, MenSC therapy showed promising and encouraging results in treating severe COVID-19. We reviewed published clinical trials and summarized the effects of MenSC therapy on severe COVID-19 with a focus on clinical and laboratory data, immune and inflammatory factors and concluded the advantages and possible risks of this procedure.

SARS-CoV-2 detection by targeting four loci of viral genome using graphene oxide and gold nanoparticle DNA biosensor.

The current COVID-19 pandemic outbreak poses a serious threat to public health, demonstrating the critical need for the development of effective and reproducible detection tests. Since the RT-qPCR primers are highly specific and can only be designed based on the known sequence, mutation sensitivity is its limitation. Moreover, the mutations in the severe acute respiratory syndrome ß-coronavirus (SARS-CoV-2) genome led to new highly transmissible variants such as Delta and Omicron variants. In the case of mutation, RT-qPCR primers cannot recognize and attach to the target sequence. This research presents an accurate dual-platform DNA biosensor based on the colorimetric assay of gold nanoparticles and the surface-enhanced Raman scattering (SERS) technique. It simultaneously targets four different regions of the viral genome for detection of SARS-CoV-2 and its new variants prior to any sequencing. Hence, in the case of mutation in one of the target sequences, the other three probes could detect the SARS-CoV-2 genome. The method is based on visible biosensor color shift and a locally enhanced electromagnetic field and significantly amplified SERS signal due to the proximity of Sulfo-Cyanine 3 (Cy3) and AuNPs intensity peak at 1468 cm-1. The dual-platform DNA/GO/AuNP biosensor exhibits high sensitivity toward the viral genome with a LOD of 0.16 ng/µL. This is a safe point-of-care, naked-eye, equipment-free, and rapid (10 min) detection biosensor for diagnosing COVID-19 cases at home using a nasopharyngeal sample.

Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines.

Viral infections are a great threat to human health. Currently, there are no effective vaccines and antiviral drugs against the majority of viral diseases, suggesting the need to develop novel and effective antiviral agents. Since the intracellular delivery of antiviral agents, particularly the impermeable molecules, such as peptides, proteins, and nucleic acids, are essential to exert their therapeutic effects, using a delivery system is highly required. Among various delivery systems, cell-penetrating peptides (CPPs), a group of short peptides with the unique ability of crossing cell membrane, offer great potential for the intracellular delivery of various biologically active cargoes. The results of numerous in vitro and in vivo studies with CPP conjugates demonstrate their promise as therapeutic agents in various medical fields including antiviral therapy. The CPP-mediated delivery of various antiviral agents including peptides, proteins, nucleic acids, and nanocarriers have been associated with therapeutic efficacy both in vitro and in vivo. This review describes various aspects of viruses including their biology, pathogenesis, and therapy and briefly discusses the concept of CPP and its potential in drug delivery. Particularly, it will highlight a variety of CPP applications in the management of viral infections.

Drug-induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies.

The world is currently facing an unprecedented pandemic caused by a newly recognized and highly pathogenic coronavirus disease 2019 (COVID-19; induced by SARS-CoV-2 virus), which is a severe and ongoing threat to global public health. Since COVID-19 was officially declared a pandemic by the World Health Organization in March 2020, several drug regimens have rapidly undergone clinical trials for the management of COVID-19. However, one of the major issues is drug-induced organ injury, which is a prominent clinical challenge. Unfortunately, most drugs used against COVID-19 are associated with adverse effects in different organs, such as the kidney, heart, and liver. These side effects are dangerous and, in some cases, they can be lethal. More importantly, organ injury is also a clinical manifestation of COVID-19 infection. These adverse reactions are increasingly recognized as outcomes of COVID-19 infection. Therefore, the differential diagnosis of drug-induced adverse effects from COVID-19-induced organ injury is a clinical complication. This review highlights the importance of drug-induced organ injury, its known mechanisms, and the potential therapeutic strategies in COVID-19 pharmacotherapy. We review the potential strategies for the differential diagnosis of drug-induced organ injury. This information can facilitate the development of therapeutic strategies, not only against COVID-19 but also for future outbreaks of other emerging infectious diseases.

Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran.

AIM: To describe the epidemiological and clinical characteristics along with outcomes of hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without diabetes. METHODS: This retrospective, single-center study included 595 consecutive hospitalized patients with confirmed COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from February 26, 2020 to March 26, 2020. Demographic data, clinical, laboratory, and radiological findings were collected and compared between patients based on diabetes status. Complications and clinical outcomes were followed up until April 4, 2020. RESULTS: From among the 595 hospitalized patients with COVID-19, the median age was 55 years and 401 (67.4%) were male. The most common symptoms included fever (419 [70.4%]), dry cough (368 [61.8%]) and dyspnea (363 [61%]). A total of 148 patients (24.9%) had diabetes, and compared with patients without diabetes, these patients had more comorbidities (eg, hypertension [48.6% vs. 22.3%; P < 0.001]); had higher levels of white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate and blood urea nitrogen, and had a higher proportion of patchy ground-glass opacity in chest computed tomography findings (52.7% vs. 25.7%; P < 0.001). Significantly, patients with diabetes had more complications and needed more respiratory support than those without diabetes (P < 0.001). At the end of the follow-up, treatment failure and death was significantly higher in patients with diabetes compared to those without diabetes (17.8% vs. 8.7%; P = 0.003). CONCLUSION: COVID-19 patients with diabetes are at a higher risk of complications and a higher in-hospital mortality during hospitalization. Diabetes status of COVID-19 patients and frequent monitoring of glycemia would be helpful to prevent deteriorating clinical conditions.