Wharton's jelly-mesenchymal stem cells treatment for severe COVID 19 patients: 1-year follow-up.

Background: Recently, attention has been focused on mesenchymal stem cells (MSC) because of their unique ability to suppress inflammation induced by cytokine storms caused by COVID-19. Several patients have been successfully treated in this manner. After one year of treatment with Wharton's jelly-derived MSC injections, this study evaluated the safety and efficacy of injecting MSCs intravenously in patients with COVID-19. Methods: This study treated four patients with severe COVID-19 with Wharton's jelly-derived mesenchymal stem cells. In this study, patients were followed up for routine tests, tumor markers, and whole-body imaging (spiral neck CT scan (with contrast), spiral chest CT scan (with & without contrast), and spiral abdominopelvic CT scan (with IV & Oral contrast)) one year after cell therapy. Results: The results indicated that lymphocyte; lymph count significantly increased, and neutrophil, ESR, ferritin, and CRP significantly decreased. LDH showed a non-significant decrease (P-value<0.05). One year after the WJ-MSC injection, the tumor markers were normal, and no tumors were observed in patients after one year. Also, the CT scan result was normal. Conclusions: In patients, no serious complications were observed after a one-year follow-up. After monitoring the patient via laboratory tests, tumor markers, and whole-body imaging, we concluded that the Wharton jelly-derived mesenchymal stem cells did not cause severe complications, including tumor formation, in severe COVID19 patients within a year. More clinical trials with higher sample sizes need to be performed on cell therapy with Wharton jelly-derived mesenchymal stem cells in the future.

Clinical and laboratory findings and PCR results in severe and non-severe COVID19 patients based on CURB-65 and WHO severity indices.

BACKGROUND: The importance of clinicolaboratory characteristics of COVID-19 made us report our findings in the Alborz province according to the latest National Guideline for the diagnosis and treatment of COVID-19 in outpatients and inpatients (trial five versions, 25 March 2020) of Iran by emphasizing rRT-PCR results, clinical features, comorbidities, and other laboratory findings in patients according to the severity of the disease. METHODS: In this study, 202 patients were included, primarily of whom 164 had fulfilled the inclusion criteria. This cross-sectional, two-center study that involved 164 symptomatic adults hospitalized with the diagnosis of COVID-19 between March 5 and April 5, 2020, was performed to analyze the frequency of rRT-PCR results, distribution of comorbidities, and initial clinicolaboratory data in severe and non-severe cases, comparing the compatibility of two methods for categorizing the severity of the disease. RESULTS: According to our findings, 111 patients were rRT-PCR positive (67.6%), and 53 were rRT-PCR negative (32.4%), indicating no significant difference between severity groups that were not related to the date of symptoms' onset before admission. Based on the National Guideline, among vital signs and symptoms, mean oxygen saturation and frequency of nausea showed a significant difference between the two groups (P < 0.05); however, no significant difference was observed in comorbidities. In CURB-65 groups, among vital signs and comorbidities, mean oxygen saturation, diabetes, hypertension (HTN), hyperlipidemia, chronic heart disease (CHD), and asthma showed a significant difference between the two groups (P < 0.05), but no significant difference was seen in symptoms. CONCLUSION: In this study, rRT-PCR results of hospitalized patients with COVID-19 were not related to severity categories. From initial clinical characteristics, decreased oxygen saturation appears to be a more common abnormality in severe and non-severe categories. National Guideline indices seem to be more comprehensive to categorize patients in severity groups than CURB-65, and there was compatibility just in non-severe groups of National Guideline and CURB-65 categories.

Cell therapy in patients with COVID-19 using Wharton's jelly mesenchymal stem cells: a phase 1 clinical trial.

BACKGROUND: Mesenchymal stem cells (MSCs) have received particular attention because of their ability to modulate the immune system and inhibit inflammation caused by cytokine storms due to SARS-CoV-2. New alternative therapies may reduce mortality rates in patients with COVID19. This study aimed to assess the safety and efficacy of injecting intravenous Wharton's jelly-derived MSCs in patients with COVID-19 as a treatment. METHODS: In this study, five patients with severe COVID-19 were treated with Wharton's jelly-derived mesenchymal stem cells (150 × 106 cells per injection). These patients were subject to three intravenous injections 3 days apart, and monitoring was done on days 0, 3, 6, and 14 in routine tests, inflammatory cytokines, and flow cytometry of CD4 and CD8 markers. A lung CT scan was performed on base and days 14 and 28. In addition, IgM and IgG antibodies against SARS-CoV-2 were measured before and after treatment. RESULTS: The results showed that IL-10 and SDF-1 increased after cell therapy, but VEGF, TGF-ß, IFN-γ, IL-6, and TNFα decreased. Routine hematology tests, myocardial enzyme tests, biochemical tests, and inflammation tests were performed for all patients before and after cell therapy on base and days 3, 6, and 14, which indicated the improvement of test results over time. COVID-19 antibody tests rose in 14 days after WJ-MSC injection. The total score of zonal involvement in both lungs was improved. CONCLUSIONS: In patients, the trend of tests was generally improving, and we experienced a reduction in inflammation. No serious complications were observed in patients except the headache in one of them, which was resolved without medication. In this study, we found that patients with severe COVID-19 in the inflammatory phase respond better to cell therapy. More extensive clinical trials should be performed in this regard. TRIAL REGISTRATION: IRCT, IRCT20190717044241N2 . Registered April 22, 2020.

Clinical and laboratory findings in COVID-19 adult hospitalized patients from Alborz province / Iran: comparison of rRT-PCR positive and negative.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was emergency turned into global public health after the first patients were detected in Wuhan, China, in December 2019. The disease rapidly expanded and led to an epidemic throughout China, followed by the rising number of cases worldwide. Given the high prevalence of COVID-19, rapid and accurate diagnostic methods are immediately needed to identify, isolate and treat the patients as soon as possible, decreasing mortality rates and the risk of public contamination by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). METHODS: This case-control study was conducted in two hospitals in Alborz Province in Iran. All recruited cases in this study were symptomatic adults hospitalized as COVID-19 patients with compatible Computed tomographic (CT) scan findings and available rRT-PCR results. The patients were recruited in this study. The patients were categorized into positive and negative rRT-PCR groups and evaluated for symptoms, initial vital signs, comorbidity, clinical and laboratory findings. Finally, the results were assessed by SPSS software. RESULTS: Between March 5 to April 5, 2020, 164 symptomatic COVID-19 patients were studied. In total, there were 111 rRT-PCR positive (67.6%) and 53 rRT-PCR negative patients (32.4%). In terms of statistics, the frequency of symptoms revealed no difference, except for cough (P.V:0.008), dizziness (PV: 0.048), and weakness (P.V:0.022). Among initial vital signs, PR (P.V:0.041) and O2 Saturation (PV: 0.014) were statistically different between the two groups. Evaluation of comorbidities revealed no difference except for hyperlipidemia (P.V:0.024). In the comparison of laboratory findings, only WBC count (PV: 0.001), lymphocyte count (PV: 0.001), and Hb (P.V:0.008) were statistically different between the two groups. CONCLUSION: In case of the negative rRT-PCR result, it is necessary to take a logical approach, and we recommended that the physician decides according to clinical manifestations, laboratory findings, and positive CT results.