Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Immunophenotyping characteristics of COVID-19 patients: Peripheral blood CD8+ HLA-DR+ T cells as a biomarker for mortality outcome.

INTRODUCTION: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed.

Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options.

Coronavirus disease 2019 (COVID-19) outbreak has become a global public health emergency and has led to devastating results. Mounting evidence proposes that the disease causes severe pulmonary involvement and influences different organs, leading to a critical situation named multi-organ failure. It is yet to be fully clarified how the disease becomes so deadly in some patients. However, it is proven that a condition called "cytokine storm" is involved in the deterioration of COVID-19. Although beneficial, sustained production of cytokines and overabundance of inflammatory mediators causing cytokine storm can lead to collateral vital organ damages. Furthermore, cytokine storm can cause post-COVID-19 syndrome (PCS), an important cause of morbidity after the acute phase of COVID-19. Herein, we aim to explain the possible pathophysiology mechanisms involved in COVID-19-related cytokine storm and its association with multi-organ failure and PCS. We also discuss the latest advances in finding the potential therapeutic targets to control cytokine storm wishing to answer unmet clinical demands for treatment of COVID-19.

SARS-CoV-2 mRNA-vaccine candidate; COReNAPCIN®, induces robust humoral and cellular immunity in mice and non-human primates.

At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN®; a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN® is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN® induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2 × 108 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN® as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies.

Neutrophil to Lymphocyte Ratio (NLR) and Derived NLR Combination: A Cost-effective Predictor of Moderate to Severe COVID-19 Progression.

Inflammation is an essential contributor to Coronavirus disease 2019 (COVID-19).   In this regard, finding a prognostic indicator is valuable because the treatment will be more effective if critical patients with high inflammation are diagnosed earlier. We aimed to evaluate some hematologic markers for COVID-19 and assess their association with the severity of the disease. A total of 154 COVID-19 patients were laboratory-confirmed and admitted to Imam Khomeini Hospital Complex, Tehran, Iran, from February 12, 2020, to April 4, 2020, and 55 healthy individuals were enrolled in the study. The severity of the patients' illnesses was classified into three subgroups according to the types of oxygen therapies (moderate (61), severe (28), and critical (43)) and examined the different ratios of total white blood cell (WBC) count, neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PLR), macrophage to lymphocyte ratio (MLR), derived NLR ratio (dNLR), and some biochemical tests. COVID-19 patients had higher levels of NLR, MLR, PLR, and dNLR than healthy subjects. receiver operating characteristic (ROC) analysis of the curve revealed that NLR and dNLR had a high diagnostic value to differentiate COVID-19 patients from healthy subjects (area under the curve [AUC]=0.923 and 0.910, respectively) and predict mortality (AUC=0.726 and 0.735, respectively). NLR and dNLR may be reliable markers to evaluate the severity of COVID-19. NLR and dNLR had a high diagnostic value for differentiating COVID-19 patients from healthy subjects, and they could predict the severity and outcome of the disease.

Nationwide population-based surveys of Iranian COVID-19 Serological Surveillance (ICS) program: The surveys protocol.

Background: Serological surveillance of COVID-19 through conducting repetitive population-based surveys can be useful in estimating and monitoring changes in the prevalence of infection across the country. This paper presents the protocol of nationwide population-based surveys of the Iranian COVID-19 Serological Surveillance (ICS) program. Methods: The target population of the surveys is all individuals ≥6 years in Iran. Stratified random sampling will be used to select participants from those registered in the primary health care electronic record systems in Iran. The strata are the 31 provinces of the country, in which sampling will be done through simple random sampling. The sample size is estimated 858 individuals for each province (except for Tehran province, which is 2574) at the first survey. It will be recalculated for the next surveys based on the findings of the first survey. The participants will be invited by the community health workers to the safe blood sampling centers at the district level. After obtaining written informed consent, 10 mL of venous blood will be taken from the participants. The blood samples will be transferred to selected reference laboratories in order to test IgG and IgM antibodies against COVID-19 using an Iranian SARS-CoV-2 ELISA Kit (Pishtaz Teb). A serologically positive test is defined as a positive IgG, IgM, or both. After adjusting for the measurement error of the laboratory test, nonresponse bias, and sampling design, the prevalence of COVID-19 will be estimated at the provincial and national levels. Also, the approximate incidence rate of infection will be calculated based on the data of both consecutive surveys. Conclusion: The implementation of these surveys will provide a comprehensive and clear picture of the magnitude of COVID-19 infection and its trend over time for health policymakers at the national and subnational levels.

Prevalence of COVID-19 in Iran: results of the first survey of the Iranian COVID-19 Serological Surveillance programme.

OBJECTIVES: This study aims to estimate the prevalence of coronavirus disease 2019 (COVID-19) in the general population of Iran. METHODS: The target population was all Iranian people aged 6 years and older in the country. A stratified random sampling design was used to select 28 314 people from among the individuals registered in the electronic health record systems used in primary health care in Iran. Venous blood was taken from each participant and tested for the IgG antibody against COVID-19. The prevalence of COVID-19 was estimated at provincial and national levels after adjusting for the measurement error of the laboratory test, non-response bias and sampling design. RESULTS: Of the 28 314 Iranians selected, 11 256 (39.75%) participated in the study. Of these, 5406 (48.0%) were male and 6851 (60.9%) lived in urban areas. The mean (standard deviation) participant age was 35.89 (18.61) years. The adjusted prevalence of COVID-19 until 20 August 2020 was estimated as 14.2% (95% uncertainty interval 13.3%-15.2%), which was equal to 11 958 346 (95% CI 11 211 011-12 746 776) individuals. The adjusted prevalences of infection were 14.6%, 13.8%, 16.6%, 11.7% and 19.4% among men, women, urban population, rural population and individuals aged 60 years or more, respectively. Ardabil, Golestan and Khuzestan provinces had the highest prevalence and Alborz, Hormozgan and Kerman provinces had the lowest. CONCLUSIONS: Based on the study results, a large proportion of the Iranian population had not yet been infected by COVID-19. The observance of hygienic principles and social restrictions should therefore continue until the majority of the population has been vaccinated.

Mesenchymal stem cell therapies for COVID-19: Current status and mechanism of action.

The outbreak of COVID-19 in December 2019, has become an urgent and serious public health emergency. At present, there is no effective treatment or vaccine for COVID-19. Therefore, there is a crucial unmet need to develop a safe and effective treatment for COVID-19 patients. Mesenchymal stem cells (MSCs) are widely used in basic science and in a variety of clinical trials. MSCs are able to engraft to the damaged tissues after transplantation and promote tissue regeneration, besides MSCs able to secrete immunomodulatory factors that suppress the cytokine storms. Moreover, the contribution of MSCs to prevent cell death and inhibit tissue fibrosis is well established. In the current review article, the potential mechanisms by which MSCs contribute to the treatment of COVID-19 patients are highlighted. Also, current trials that evaluated the potential of MSC-based treatments for COVID-19 are briefly reviewed.

Hypothesis for the management and treatment of the COVID-19-induced acute respiratory distress syndrome and lung injury using mesenchymal stem cell-derived exosomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronaviridae that causes respiratory disorders. After infection, large amounts of inflammatory cytokines are secreted, known as the cytokine storm. These cytokines can cause pulmonary damage induced by inflammation resulting in acute respiratory distress syndrome (ARDS), and even death. One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. But our suggestion is using MSCs-derived exosomes. Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don't have problems associated to cell maintenance and injections. For investigation the hypothesis, MSCs should be isolated from tissues and characterized. Then, the exosomes should be isolated from the supernatants and characterized. These exosomes should be injected into a transgenic animal for COVID-19. In the final section, lung function assessment, histological examination, micro-CT, differential leukocyte, viral load analysis, cytokine assay, and CRP level analysis can be investigated. COVID-19 treatment is currently focused on supportive therapies and no vaccine has been developed for it. So, numerous researches are needed to find potential therapies. Since the pathogenesis of this disease was identified in previous studies and can cause lung injury with ARDS, investigation of the therapeutic approaches that can suppress inflammation, cytokine storm and ARDS can be helpful in finding a novel therapeutic approach for this disease.