Five consecutive epidemiological waves of COVID-19: a population-based cross-sectional study on characteristics, policies, and health outcome.

BACKGROUND: This study was conducted with the intension of providing a more detailed view about the dynamics of COVID-19 pandemic. To this aim, characteristics, implemented public health measures, and health outcome of COVID-19 patients during five consecutive waves of the disease were assessed. METHODS: This study was a population-based cross-sectional analysis of data on adult patients who were diagnosed with COVID-19 during five waves of the disease in Iran. Chi-squared test, One-way ANOVA, and Logistic Regression analysis were applied. A detailed literature review on implemented public health policies was performed by studying published documents and official websites responsible for conveying information about COVID-19. RESULTS: Data on 328,410 adult patients was analyzed. Main findings indicated that the probability of dying with COVID-19 has increased as the pandemic wore on, showing its highest odd during the third wave (odds ratio: 1.34, CI: 1.283-1.395) and has gradually decreased during the next two waves. The same pattern was observed in the proportion of patients requiring ICU admission (P < 0.001). First wave presented mainly with respiratory symptoms, gastrointestinal complaints were added during the second wave, neurological manifestations with peripheral involvement replaced the gastrointestinal complaints during the third wave, and central nervous system manifestations were added during the fourth and fifth waves. A significant difference in mean age of patients was revealed between the five waves (P < 0.001). Moreover, results showed a significant difference between men and women infected with COVID-19, with men having higher rates of the disease at the beginning. However, as the pandemic progressed the proportion of women gradually increased, and ultimately more women were diagnosed with COVID-19 during the fifth wave. Our observations pointed to the probability that complete lockdowns were the key measures that helped to mitigate the virus spread during the first twenty months of the pandemic in the country. CONCLUSION: A changing pattern in demographic characteristics, clinical manifestations, and severity of the disease has been revealed as the pandemic unfolded. Reviewing COVID-19-related public health interventions highlighted the importance of immunization and early implementation of restrictive measures as effective strategies for reducing the acute burden of the disease.

Urban and sub-urban disparities in health outcomes among patients with COVID-19; a cross-sectional study of 234 418 patients in Iran.

BACKGROUND: It remains crucial to understand socio-demographic determinants of COVID-19 infection to improve access to care and recovery rates from the disease. This study aimed to investigate the urban and sub-urban disparities associated with COVID-19 in patients visiting healthcare facilities in the province of Tehran, Iran. METHODS: Data from 234 418 patients who were diagnosed with COVID-19 infection from March 2020 to March 2021 in the province of Tehran were used in this analysis. Descriptive statistics were used to describe the characteristics of the study population. Chi-Squared test was applied to examine the association of study variables with residing area. Independent samples t-test was performed to compare mean age of patients in urban and sub-urban areas. Multiple Logistic Regression model was applied to examine the association of study variables with disease outcome. RESULTS: Overall, most patients resided in the urban settings (73%). Mean age of patients was significantly lower in sub-urban areas compared to their counterparts in urban settings (49 ± 23.1 years versus 53 ± 21.1 years, P < 0.001). Positive PCR test results were more common in urban areas (48.5% versus 41.3%, P < 0.001). Yet, sub-urban settings had higher rates of positive chest CT scan reports (62.8% versus 53.4%, P < 0.001). After accounting for age and sex covariates, residing in urban areas was associated with higher likelihood of being admitted to an ICU (OR = 1.27, CI: 1.240-1.305). Yet, a greater vulnerability to fatal outcome of COVID-19 infection was shown in patients living in sub-urban areas (OR = 1.13, CI: 1.105-1.175). CONCLUSIONS: This study revealed a clear disparity in the health outcome of patients infected with COVID-19 between urban and sub-urban areas.

Sociodemographic determinants and clinical risk factors associated with COVID-19 severity: a cross-sectional analysis of over 200,000 patients in Tehran, Iran.

BACKGROUND: Defining socio-demographic factors, clinical presentations and underlying diseases associated with COVID-19 severity could be helpful in its management. This study aimed to further clarify the determinants and clinical risk factors of the disease severity in patients infected with COVID-19. METHODS: A multi-centre descriptive study on all patients who have been diagnosed with COVID-19 in the province of Tehran from March 2020 up to Dec 2020 was conducted. Data on socio-demographic characteristics, clinical presentations, comorbidities, and the health outcomes of 205,654 patients were examined. Characteristics of the study population were described. To assess the association of study variables with the disease severity, the Chi-Squared test and Multiple Logistic Regression model were applied. RESULTS: The mean age of the study population was 52.8 years and 93,612 (45.5%) were women. About half of the patients have presented with low levels of blood oxygen saturation. The ICU admission rate was 17.8% and the overall mortality rate was 10.0%. Older age, male sex, comorbidities including hypertension, cancer, chronic respiratory diseases other than asthma, chronic liver diseases, chronic kidney diseases, chronic neurological disorders, and HIV/AIDS infection were risk markers of poor health outcome. Clinical presentations related with worse prognosis included fever, difficulty breathing, impaired consciousness, and cutaneous manifestations. CONCLUSION: These results might alert physicians to pay attention to determinants and risk factors associated with poor prognosis in patients with COVID-19. In addition, our findings aid decision makers to emphasise on vulnerable groups in the public health strategies that aim at preventing the spread of the disease and its mortalities.

The most places at risk surrounding the COVID-19 treatment hospitals in an urban environment- case study: Tehran city.

Investigations on the spatial patterns of COVID-19 spreading indicate the possibility of the virus transmission by moving infected people in an urban area. Hospitals are the most susceptible locations due to the COVID-19 contaminations in metropolises. This paper aims to find the riskiest places surrounding the hospitals using an MLP-ANN. The main contribution is discovering the influence zone of COVID-19 treatment hospitals and the main spatial factors around them that increase the prevalence of COVID-19. The innovation of this paper is to find the most relevant spatial factors regarding the distance from central hospitals modeling the risk level of the study area. Therefore, eight hospitals with two service areas for each of them are computed with [0-500] and [500-1000] meters distance. Besides, five spatial factors have been considered, consist of the location of patients' financial transactions, the distance of streets from hospitals, the distance of highways from hospitals, the distance of the non-residential land use from the hospitals, and the hospital patient number. The implementation results revealed a meaningful relation between the distance from the hospitals and patient density. The RMSE and R measures are 0.00734 and 0.94635 for [0-500 m] while these quantities are 0.054088 and 0.902725 for [500-1000 m] respectively. These values indicate the role of distance to central hospitals for COVID-19 treatment. Moreover, a sensitivity analysis demonstrated that the number of patients' transactions and the distance of the non-residential land use from the hospitals are two dominant factors for virus propagation. The results help urban managers to begin preventative strategies to decrease the community incidence rate in high-risk places.

COVID-19 in pregnancy: A cross-sectional study on clinical features, disease severity, and health outcome.

Assessing the impact of coronavirus disease 2019 (COVID-19) reveals unique challenges for pregnant women, who experience distinct clinical manifestations and health outcomes compared to their non-pregnant counterparts. We aimed to evaluate the clinical features, disease severity, and health outcomes of COVID-19 in pregnant women and compare them to those of non pregnant women. In this population-based study, we included all women diagnosed with COVID-19 across the province of Tehran during the first two years of the epidemic. Descriptive statistics, the chi-squared test, and the logistic regression model were applied. Overall, 79,338 non-pregnant women and 3249 pregnant women diagnosed with COVID-19 were included. Pregnant women were most commonly in the age group of 25 - 34 years (54%, n = 1758), while the age group of 34-44 had the highest representation among non-pregnant women (56%, n = 44,492). After accounting for age and comorbidities, pregnancy was associated with an increased risk of requiring intensive care (odds ratio [OR] 1.38, confidence interval [CI] 1.223 - 1.564). However, the probability of dying due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was lower in pregnant women compared to non-pregnant women (OR 0.55, CI 0.394-0.793). Cough (41%) and fever (30%) were the most frequent clinical presentations in pregnant women, whereas cough (57%) and muscle ache (38%) were the most common symptoms in non-pregnant women. Furthermore, diarrhea (P < 0.001) and skin lesions (P < 0.001) were reported more frequently by pregnant patients than non-pregnant patients. A significant prevalence of diabetes (P < 0.001), hypertension (P < 0.001), cancers (P < 0.001), and chronic hematological diseases (P < 0.001) was observed in pregnant patients. In conclusion, COVID-19-infected pregnant women exhibit different clinical manifestations and a more severe clinical course but have better health outcomes compared to their non-pregnant counterparts.

Safety and possible outcome assessment of autologous Schwann cell and bone marrow mesenchymal stromal cell co-transplantation for treatment of patients with chronic spinal cord injury.

BACKGROUND AIMS: Cell replacement therapy has become a promising issue that has raised much hope in the regeneration of central nervous system injury. Evidence indicates that successful functional recovery in patients with spinal cord injury will not simply emphasize a single therapeutic strategy. Therefore, many recent studies have used combination strategies for spinal cord regeneration. METHODS: We assessed the safety and feasibility of a bone marrow mesenchymal stromal cell and Schwann cell combination for the treatment of patients with chronic spinal cord injury. Eight subjects who received a complete traumatic spinal cord injury (American Spinal Injury Association [ASIA] classification A) enrolled in this study. The patients received this autologous combination of cells directly into the injury site. The mean duration of follow-up was approximately 24 months. RESULTS: No magnetic resonance imaging evidence of neoplastic tissue overgrowth, syringomyelia or psuedomeningocele in any of the patients was seen during the study. There was no deterioration in sensory or motor function in any of the patients during the course of the study. Three patients had negligible improvement in ASIA sensory scale. No motor score improvement and no change in ASIA classification was seen. The patients had widely subjective changes in the course of the study such as urination and defecation sensation and more stability and trunk equilibrium in the sitting position. CONCLUSIONS: There were no adverse findings at least 2 years after autologous transplantation of Schwann cell and mesenchymal stromal cell combination into the injured spinal cord. It appears that the use of this combination of cells is safe for clinical application to spinal cord regeneration.

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma.

Introduction: The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects. Case presentation: A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days). Conclusion: The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal). Trial registration: IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.

Migrant Health and COVID-19 Pandemic: A Cross-sectional Study of Characteristics, Clinical Features, and Health Outcome from Iran.

BACKGROUND: As the pandemic unfolds, major concerns remain with those in disadvantaged positions who may be disproportionately affected. This paper aimed to present the characteristics of COVID-19 immigrant patients and investigate whether they were disproportionately affected by COVID-19 pandemic. METHODS: A cross-sectional study was performed using data on 589,146 patients diagnosed with COVID-19 in Iran. Descriptive analyses were used to summarize the study population's characteristics. Chi-squared test and logistic regression model were applied. RESULTS: After accounting for possible confounding covariates, being an immigrant was significantly associated with increased risk of death due to COVID-19 (OR 1.64, CI 1.568-1.727). When compared to Iranian-born patients, the prevalence of low blood oxygen levels on admission was higher among immigrant patients (53.9% versus 47.7%, P value < 0.001). Moreover, greater proportions of immigrants who were diagnosed with COVID-19 were admitted to an ICU (17% versus 15.8%, P value < 0.001). Patients aged 65 and above were the largest age category in both populations. However, there was a significant difference between the age profiles of patients, with children under the age of eighteen presenting 16% of immigrant patients vs 6.6% of Iranian-born patients (P value < 0.001). In both groups, more men were affected by COVID-19 than women, yet the sex bias was more prominent for migrant patients (P value < 0.001). CONCLUSION: The evidence from this study revealed that immigrant patients infected with COVID-19 were more likely to suffer from severe health outcome of the disease compared to Iranian-born patients.

Cauda equina syndrome due to herpes simplex virus type 2-associated meningoradiculitis (Elsberg syndrome) after posterior lumbar spinal fusion surgery: Case report and review of literature.

Elsberg syndrome is a rare but well-defined clinical condition, including acute or subacute lumbosacral meningoradiculitis, which might be accompanied by myelitis and is often associated with herpes simplex virus type 2 (HSV-2) infection. We report the case of an immunocompetent 24-year-old man who presented with perineal pain, saddle hypoesthesia, and urinary retention associated with Elsberg syndrome due to HSV-2 infection 20-day after the posterior lumbar spinal fusion surgery. Lumbar magnetic resonance imaging (MRI) with gadolinium enhancement showed mildly enhanced and swollen right sacral nerve roots. One week after the admission, electromyography and nerve conduction studies (EMG-NCS) demonstrated severe axonal damage and radiculopathy at right S3 and S4 roots. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, elevated protein, positive HSV-2 IgG index, and positive HSV-2 polymerase chain reaction (PCR). The patient was treated with intravenous acyclovir for 14 days and showed a gradual improvement in anal sphincter control and urination. Therefore, according to our findings, surgery might have an immunosuppressing role, and in cases with symptoms of cauda equina syndrome (CES) and systemic infection, in the postoperative setting, viral meningoradiculitis should be considered.

Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.