Expression Pattern of Inflammatory and Anti-Inflammatory Cytokines and Key Differential Transcription Factors in Peripheral Blood Mononuclear Cells of Iranian Coronavirus Disease 2019 Patients with Different Disease Severity.

The purpose of this research was to investigate the gene expression levels of inflammatory cytokines interferon (IFN)γ, tumor necrosis factor (TNF)α, interleukin (IL)1ß, IL2, IL6, IL8, and IL17, and anti-inflammatory cytokines IL4, IL10, IFNα, and IFNß, as well as relevant key transcription factors (TFs), including GATA3, PU1, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), BCL6 (B cell lymphoma 6 protein), FOXP3 (forkhead box P3), RORγt, and T-bet (T-box expressed in T cell) in Iranian patients with moderate and severe coronavirus disease 2019 (COVID-19). Fifty-six patients with COVID-19, and 25 healthy controls (HCs) age and sex matched were investigated. Based on the interim guidance of COVID-19 from the World Health Organization, the patients were classified into 33 moderate and 23 severe patients with COVID-19. The gene expression levels of cytokines and relevant TFs were quantified in peripheral blood mononuclear cells by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression levels of TFs RoRγ (RAR-related orphan nuclear receptor γ), NF-κB, and T-bet were significantly higher in patients with COVID-19 compared with HCs. Furthermore, the gene expression levels of cytokines, including IL2, IFNγ, IL6, TNFα, IL1ß, IL8, and IL17, were significantly higher in patients with COVID-19 than HCs. However, there was a significant increase for IL6, TNFα, and IL17 in severe compared with moderate patients with COVID-19. Finally, The Spearman correlation analysis revealed a significantly positive correlation for IL6 and TNFα, IL6 and IL2, IL6, IFNγ, and IL2 and IFNγ. These data suggest that expression of IL6, TNFα, and IL17 as well as the synergic effect of elevated values of IL2 and IFNγ should be considered in the treatment and management of patients with severe COVID-19.

The effects of antihypertensive medications on severity and outcomes of hypertensive patients with COVID-19.

In Covid-19 pandemic, specific comorbidities are associated with the increased risk of worse outcomes and increased severity of lung injury and mortality. the aim of this study was to investigate the effects of antihypertensive medications on the severity and outcomes of hypertensive patients with COVID-19. This retrospective observational study conducted on patients with COVID-19 who referred to Afzalipour Hospital, Kerman, Iran during the six months from 19 February 2020 to 20 July 2020. The data were collected through medical chart reviews. We assessed 265 patients with Covid-19 and they stratified based on hypertension and type of antihypertension medications. The data were described and Student's t-test, Mann-Whitney U and Fisher exact test were run to compare the patients 'demographical and clinical information. The qualitative variables were compared using the by SPSS software version 23. The results of the present study showed that hypertension was a prevalent comorbidity among patients with COVID-19 and hypertensive patients compared to other patients without any comorbidity who were older (P-value: 0.03). The oxygen saturation was higher for the patients in the control group than hypertensive patients (P-value: 0.01). The severity of COVID-19 and its outcome were not different between the patients who took or did not take antihypertensive medications and also the type of antihypertensive medications. Hypertensive patients did not show any significant difference in survival, hospital stay, ICU admission, disease severity, and invasive medical ventilation in other normotensive patients with COVID-19.

Type-I interferons in the immunopathogenesis and treatment of Coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is currently the major global health problem. Still, it continues to infect people globally and up to the end of February 2022, over 436 million confirmed cases of COVID-19, including 5.95 million deaths, were reported to the world health organization (WHO). No specific treatment is currently available for COVID-19, and the discovery of effective therapeutics requires understanding the effective immunologic and immunopathologic mechanisms behind this infection. Type-I interferons (IFN-Is), as the critical elements of the immediate immune response against viral infections, can inhibit the replication and spread of the viruses. However, the available evidence shows that the antiviral IFN-I response is impaired in patients with the severe form of COVID-19. Moreover, the administration of exogenous IFN-I in different phases of the disease can lead to various outcomes. Therefore, understanding the role of IFN-I molecules in COVID-19 development and its severity can provide valuable information for better management of this disease. This review summarizes the role of IFN-Is in the pathogenesis of COIVD-19 and discusses the importance of autoantibodies against this cytokine in the spreading of SARS-CoV-2 and control of the subsequent excessive inflammation.

Efficacy of the barley-based remedy, a Persian medicine formula, in coronavirus disease 2019 (COVID-19) hospitalized patients: An open-labeled randomized controlled trial.

Background: With the pandemic of coronavirus disease 2019 (COVID-19), and the growing attention of people around the world to the use of traditional and complementary medicines to control of the disease, evaluating the effectiveness of these treatments has received special attention. Aim: This study aimed to assess the clinical efficacy of a barley-based (Hordeum vulgare) remedy combined with conventional medicine in comparison to the conventional therapy in confirmed COVID-19 patients. Materials and methods: Seventy COVID-19 patients were randomly divided into barley-based remedy plus conventional medicine (barley-based remedy group) and conventional therapy (control group). Both groups were treated for 5 days. The outcomes were oxygen saturation, main symptoms (fever, respiratory rate, cough, and fatigue), and laboratory data (lymphocytic count, and CRP); they were measured for 6 days. Results: In comparison to the control group, the oxygen saturation level in the barley-based remedy group significantly increased, from the second day of the intervention (P < 0.05). The herbal remedy significantly improved fatigue from the third day (P < 0.05). Meanwhile, the severity and frequency of cough between the groups were not significantly different. The herbal remedy had no significant effect on the CRP and the lymphocytic count of every time points of measurement. The average of respiratory rate and temperature of patients were in the normal range in both groups during the intervention. Conclusion: Barley-based remedy could significantly enhance the blood oxygen saturation and reduce fatigue. However, it needs to be confirmed by large sample size trials.

Robust antimicrobial photodynamic therapy with curcumin-poly (lactic-co-glycolic acid) nanoparticles against COVID-19: A preliminary in vitro study in Vero cell line as a model.

BACKGROUND: In this study, the ability of antimicrobial photodynamic therapy (aPDT) as a treatment approach and adjuvant therapy using curcumin-poly (lactic-co-glycolic acid) nanoparticles (Cur@PLGA-NPs) to inactivate Coronavirus disease 2019 (COVID-19) in plasma was investigated. Furthermore, to verify whether the quality requirement of aPDT-treated plasma is acceptable, the differences of the levels of clotting factors, total plasma proteins, and anti-A and/or anti-B antibodies titrations in plasma of patient before and after aPDT treatment were investigated. MATERIALS AND METHODS: Cur@PLGA-NPs was synthesized using Electrospinning process and characterized by different analysis including Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), and Fourier Transform Infrared (FTIR) spectroscopy assays. The presence of the SARS-CoV-2 in the plasma samples of patients suspected of having COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Then, the treated plasma samples with Cur@PLGA-NPs plus blue laser were exposed to Vero cells. Eventually, cell cytotoxicity and apoptotic effects of treated Vero cells were evaluated. Levels of clotting factors including prothrombin time (PT) and activated partial thromboplastin time (APTT), total plasma proteins, and anti-A and/or anti-B antibodies measurements were performed using the coagulometer, method of Bradford, and titration procedure, respectively. RESULTS: The presence of SARS-CoV-2 was positive in 84.3 % of samples. Different concentrations of Cur@PLGA-NPs (3, 5, 7, and 10 % wt.), the irradiation times of blue laser (1, 3, and 5 min), and aPDT with the maximum dosed of blue laser light (522.8 J/cm2) plus 10 % wt. Cur@PLGA-NPs had no cytotoxicity. Although there were significant cell degradation and apoptotic effects in treated Vero cells with treated plasma using 10 % wt. Cur@PLGA-NPs, and a blue laser at an energy density of 522.8 J/cm2, no visible changes in cells and apoptosis were observed following aPDT. Total plasma protein content, PT, APTT, and anti-A and/or anti-B antibodies titers showed no significant changes (P > 0.05 for all comparisons) in treated plasma as compared to untreated plasma. CONCLUSION: aPDT exhibited in vitro anti-COVID-19 activities in the treated plasma containing SARS-COV-2 without Vero cell apoptosis and any adverse effects on plasma quality in aPDT-exposed plasma.

Evaluating the efficacy and safety of the myrtle (Myrtus communis) in treatment and prognosis of patients suspected to novel coronavirus disease (COVID-19): study protocol for a randomized controlled trial.

BACKGROUND: Since December 2019, the outbreak of coronavirus pneumonia was observed in China and quickly propagate in all of the world. Nowadays, many trials are underway on this disease in which the efficacy of various therapeutic remedies including chemical or natural agents as well as different non-pharmacological methods such as acupuncture are evaluated. This study aims at investigating the effect of M. communis fruit for treatment of COVID-19 disease. METHODS: We are performing an open-label randomized controlled trial on outpatients clinically suspected to COVID-19 disease in the age range of 18-65 years old with mild to moderate symptoms and without respiratory distress. Patients in both groups (M. communis and control) receive conventional therapy, but those in M. communis group get M. communis preparation in addition to conventional therapy. Intervention will continue for 5 days and the study outcomes including clinical status as well as mortality rate and adverse effects will be measured up to 14 days. DISCUSSION: The protocol describes the design of an ongoing randomized controlled trial to establish the evidence for the usage of water extract of M. communis fruit in clinically suspected COVID-19 disease and identify any safety concerns. TRIAL REGISTRATION: The trial has been registered at the Iranian Registry of Clinical Trials website under the code IRCT20180923041093N3 on March 28th, 2020 ( https://www.irct.ir/trial/46721 ). The results will be disseminated through manuscript publications and presentations to scientific meetings.