Investigating the psychological effects of home quarantine during the early peaks of the COVID-19 pandemic: a survey from Iran.

We assessed psychological symptoms among individuals who were quarantined during early coronavirus disease 2019 (COVID-19) peaks. This cross-sectional study was performed during April-October 2020 in Iran. We surveyed 100 individuals with COVID-19 patients in their families and 100 others with health conditions associated with a higher risk of developing critical forms of COVID-19 infection, who have completed at least 14 days of home quarantine. Validated Persian versions of the 21-item Depression, Anxiety, and Stress and 22-item Impact of Event Scale-Revised were used to measure the symptoms of depression, anxiety, stress and distress. The rates of stress, anxiety, depression and quarantine-related distress were 46.5, 48.5, 57.0 and 80.5%, respectively; however, they were not significantly different between the contact and no-contact groups. Female sex and being unemployed were significantly associated with quarantine-related distress, P = 0.007 and P = 0.018, respectively. Independent risk factors for anxiety were a history of medical comorbidity ( P = 0.025) and contact with COVID-19 patients ( P = 0.007). Findings show high prevalence rates of psychological symptoms among quarantined individuals, regardless of whether they had contact with COVID-19 patients or not. Female sex and unemployment were risk factors for quarantine-related distress.

Specific Clinical and Immunological Changes Following Mesenchymal Stem Cell Transplantation in COVID-19-induced Acute Respiratory Distress Syndrome Patients: A Phase-I Clinical Trial.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1×  cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells.  These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: a successful phase 1, control-placebo group, clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild-moderate COVID-19-induced ARDS patients. METHODS: Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × [Formula: see text] cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. RESULTS: During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period. CONCLUSION: Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).

An 18-Month Epidemiologic Survey of 3364 Deceased COVID-19 Cases; a Retrospective Cross-sectional Study.

Introduction: The COVID-19 pandemic has been considered an international problem. This study aimed to survey the demographic and clinical characteristics of the deceased COVID-19 patients. Methods: The present cross-sectional study was performed on all deceased COVID-19 patients who died in Imam Reza Hospital, Mashhad, Iran, from March 20, 2020, to September 23, 2021. Their data, including age, gender, complaints, and clinical symptoms at the time of admission, as well as information at the time of death (hour, shift, holiday/non-holiday) were analyzed and reported. Results: 3364 deaths due to COVID-19 have been registered during the study period (60.46% male). The patients' mean age was 66.99±16.97 (range: 1-101) years (92.7% of them were Iranian). The mortality at night shifts was less than day shifts (1643 vs. 1721). The average amount of deaths/day on holidays and workdays was (5.63 vs. 6.24). The number of deaths varied during the various hours of the day and night. Diabetes and cardiovascular diseases were the most common confounding factors, which were observed in 22.44% and 15.36% of the cases, respectively. Conclusion: Based on the findings of this series, COVID-19 mortality was frequently observed in male patients, those with the mean age of 66.99 years, morning shifts, and workdays.

Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin, a natural polyphenolic compound, is proposed as a potential treatment option for patients with coronavirus disease by inhibiting the entry of virus to the cell, encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. In this study, the efficacy and safety of nanocurcumin oral formulation has been evaluated in patients with mild-moderate Coronavirus disease 2019 (COVID-19) in outpatient setting. METHODS: In this triple-blind randomized placebo-controlled clinical trial, sixty mild to moderate COVID-19 patients in outpatient setting who fulfilled the inclusion criteria were randomly allocated to treatment (n = 30) group to receive oral nanocurcumin formulation (Sinacurcumin soft gel which contains 40 mg curcuminoids as nanomicelles), two soft gels twice a day after food for 2 weeks or placebo (n = 30) group. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period and compared between two groups. RESULTS: All symptoms except sore throat resolved faster in the treatment group and the difference was significant for chills, cough and smell and taste disturbances. The CRP serum level was lower in the treatment group at the end of two weeks and the lymphocyte count was significantly higher in treatment group. No significant adverse reaction reported in the treatment group. CONCLUSION: Oral nanoformulation of curcumin can significantly improve recovery time in patients with mild to moderate COVID-19 in outpatient setting. Further studies with larger sample size are recommended.

Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies.

The Covid-19 disease has recently become one of the biggest challenges globally, and there is still no specific medication. Findings showed the immune system in severe Covid-19 patients loses regulatory control of pro-inflammatory cytokines, especially IL-6 production, called the "Cytokine storm" process. This process can cause injury to vital organs, including lungs, kidneys, liver, and ultimately death if not inhibited. While many treatments have been proposed to reduce cytokine storm, but the safety and effectiveness of each of them are still in doubt. Mesenchymal stem cells (MSCs) are multipotent cells with self-renewal potential capable of suppressing overactive immune responses and leading to tissue restoration and repair. These immuno-modulatory properties of MSCs and their derivatives (like exosomes) can improve the condition of Covid-19 patients with serious infectious symptoms caused by adaptive immune system dysfunction. Many clinical trials have been conducted in this field using various MSCs around the world. Some of these have been published and summarized in the present article, while many have not yet been completed. Based on these available data, MSCs can reduce inflammatory cytokines, increase oxygen saturation, regenerate lung tissue and improve clinical symptoms in Covid-19 patients. The review article aims to collect available clinical data in more detail and investigate the role of MSCs in reducing cytokine storms as well as improving clinical parameters of Covid-19 patients for use in future clinical studies.

Ocular Manifestations of Hospitalized Patients with COVID-19 in Northeast of Iran.

PURPOSE: To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the Northeast of Iran. METHODS: In a cross-sectional, observational study all consecutive patients with confirmed COVID-19 diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular examinations (external and slit) were randomly performed for the patients who were admitted to the Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum chemistry results were collected. RESULTS: A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23-96 years) and almost equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and 22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyperemia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at least one ocular manifestation had significantly higher blood urea levels at the time of admission compared to those with no obvious ocular involvement (median: 41.5, IQR: 28-66.3 vs. median: 33, IQR: 23.8-51.8, P = .023). Moreover, a significant difference was observed in the total white blood cell count, lymphocyte percent, neutrophil count, Erythrocyte Sedimentation Rate (ESR), and blood urea level between patients with positive and negative Polymerase Chain Reaction (PCR) for SARS-CoV-2 virus. None of the patients reported ocular symptoms prior to systemic involvement. The proportion of patients with at least one ocular manifestation was significantly higher in those admitted in the ICU compared to the non-ICU wards. wards. While conjunctival hyperemia was the most prevalent ocular finding in all patients, chemosis was the most common ocular manifestation in ICU admitted patients. CONCLUSION: Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it seems important to involve ophthalmologist in the diagnosis and management of these patients.