Menstrual Blood-Derived Mesenchymal Stem Cell Therapy for Severe COVID-19 Patients.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), was declared a global pandemic in March 2020 and resulted in more than 6 million deaths worldwide to date. Although several vaccines were produced against COVID-19 and many therapeutic protocols were developed for the management of this respiratory infection, COVID-19 pandemic has still remained an unresolved problem with the emergence of new variants of SARS-CoV-2, especially vaccine-resistant variants. Probably, end of the COVID-19 needs effective and certain treatments which were undiscovered to date. According to immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) have been considered a therapeutic approach to suppressing cytokine storm caused by SARS-CoV-2 and the treatmet of severe COVID-19. Following intravenous (IV) infusion of MSCs, cells entrap in the lung, guard alveolar epithelial cells, suppress pulmonary fibrosis and improve lung dysfunction. The human menstrual blood-derived stem cells (hMenSCs) as a novel source of MSCs are collected by noninvasive, painless, and easy way without ethical issues. MenScs are an abundant and cheap source with a high proliferation rate and differentiation ability into multiple cell lineages. Regarding immunomodulatory and anti-inflammatory properties, regenerative ability and low immunogenicity, these cells exhibit great potential in the treatment of various diseases. Some clinical trial studies have begun using MenSCs to treat severe COVID-19. According to these trials, MenSC therapy showed promising and encouraging results in treating severe COVID-19. We reviewed published clinical trials and summarized the effects of MenSC therapy on severe COVID-19 with a focus on clinical and laboratory data, immune and inflammatory factors and concluded the advantages and possible risks of this procedure.

Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

Clinical Effects of COVID-19 on Hematopoietic Stem Cell Transplant Outcomes in Pediatric Patients.

Coronavirus disease 2019 is the third zoonotic acute respiratory disease after SARS virus and Middle East respiratory syndrome. Most cases are mild in healthy children. In contrast, the infection is more severe in patients with underlying health conditions. Because there are few posttransplant reports in hematopoietic stem celltransplant patients, here we described COVID19 infection in 4 confirmed cases among pediatric hematopoietic stem cell transplant recipients: 3 boys and 1 girl with a median age of 6 years. Three patients presented with symptoms of lower respiratory tract disease, whereas 1 patient presented with extrapulmonary symptoms without fever or pulmonary involvement. All of the patients were on immunosuppressivedrugs, ie, 1patientforgraft-versus-hostdisease prophylaxis and 3 patients for graft-versus-host disease treatment.Thosewhowerediagnosedwith active graftversus-hostdisease requiredmechanical ventilationand intensive care. Two patients died from multiple organ dysfunction and resistant coinfection, and 1 patient developed pulmonary hypertension and mild cardiomegaly and remained at the hospital for more than 2 months, whereas the patient with no graft-versus-host disease was discharged and recovered. Our findings showed that COVID-19 infection among hematopoietic stem cell transplant recipients may be more severe and associatedwithlong-termhospitalization and complications. Active graft-versus-hostdisease, coinfections, and long-term use of immunosuppressive agents are risk factors for poor outcomes.

COVID-19 in transplant recipient children: An Iranian referral hospital-based study.

To our knowledge, there is still very limited information on the severity, mortality, laboratory, and radiologic findings of COVID-19 infection in transplant patients, particularly children. In this study, we report and analyze 7 transplant recipients with laboratory-confirmed COVID-19 infection. The median age was 7.5 years (IQR: 31month-10 years), and 71% of the patients were male. All cases presented with a fever. The median duration of fever before admission was 2 days (IQR:1-8 days). Five patients (71%) experienced cough and dyspnea. Lymphocytopenia (Median of 0.6 (IQR: 0.14-2.0× 109 cells per L) and thrombocytopenia (Median of 65 (IQR: 49-201× 109 cells per L) were the most common CBC findings (both seen in 5 out of the 7 patients. Among 4 of the patients who underwent CT scans, 2 had ground glass opacity and consolidations. The mean number of lobe involvement in our patients was 3(0-5), and 75% of the cases showed bilateral lung involvement in the imaging. In 4 patients (51%) the disease course manifested severely, and 2 patients are now deceased (28.6%). In conclusion, immunocompromised pediatric subgroups may experience higher rates of disease severity and mortality in comparison with the immunocompetent pediatric population.

Coronavirus Disease 2019 (COVID-19) in Children: Prevalence, Diagnosis, Clinical Symptoms, and Treatment.

In this article, we have reviewed the prevalence, diagnosis, symptoms, and treatment of COVID-19 in children. The incidence of COVID-19 among children under 18 years was 2.1% based on the reported studies, where the mortality rate in the same age group was 0.2%. No death has been reported in children under 9-years old. There are some articles that report children with COVID-19 having symptoms similar to Kawasaki's disease. In these cases, heart complications were observed. The best markers for diagnosing the severity of the disease in children are the levels of bilirubin and hepatic enzymes. Large number of angiotensin converting enzyme 2 (ACE2) receptors on cell surfaces, effective innate immune system, and high level of blood lymphocyte have been reported to be the potent reasons for lower incidence of severe symptoms of COVID-19 among children. Children can very well be the carriers of this virus. Children with severe COVID-19 clinical symptoms, especially those suffering from pneumonia, must be hospitalized similar to adults, while quarantine is required for those having mild symptoms. Antiviral medication (lopinavir, darunavir, favipiravir, remdesivir, ribavirin, oseltamivir, tocilizumab, and umifenovir), ACE inhibitors, interferon-α2b, co-therapy with azithromycin, inhaling iNO, and oxygen therapy can be used for treatment. For the treatment of children without any clinical and infection symptoms, home isolation protocol has been recommended.