First case of COVID-19 infused with hESC derived immunity- and matrix-regulatory cells.
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ABSTRACT:
SUBMITTER: Wu J
PROVIDER: S-EPMC7645847 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation. In the present study, the antioxidative and anti-inflammatory properties and the therapeutic effect of the secretome of hESC-MSC-IMRC-derived conditioned culture medium (CM) (hESC-MSC-IMRC-CM) were investigated. Results revealed the capacities of hESC-MSC-IMRC-CM to reduce bleomycin (BLM)-induced reactive oxygen species (ROS), extracellular matrix (ECM) deposition, and epithelial-mesenchymal transition (EMT) in A549 cells. The administration of concentrated hESC-MSC-IMRC-CM significantly alleviated the pathogenesis of PF in lungs of BLM-injured mice, as accessed by pathohistological changes and the expression of ECM and EMT. A mechanistic study further demonstrated that the hESC-MSC-IMRC-CM was able to inhibit BLM-induced ROS and pro-inflammatory cytokines, accompanied by a reduced expression of Nox4, Nrf2, Ho-1, and components of the Tlr4/MyD88 signaling cascade. These results provide a proof of concept for the hESC-MSC-IMRC-derived secretome treatment of PF, in part mediated by their antioxidative and anti-inflammatory effects. This study thus reinforces the development of ready-to-use, cell-free hESC-MSC-IMRC secretome biomedicine for the treatment of PF in clinical settings.
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Project description:BackgroundWith their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts.MethodsWe derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts.FindingsCP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts.InterpretationThis strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line.FundingNSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen "Sanming" Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2-10559).
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Project description:The article represents coronavirus spread log history. The duration, coronavirus takes to spread from one country to another country, could be seen in this dataset and could predicted the same for future pandemics through this dataset. It is highly dependent on the cabalistic number of variables that is the main navel of these datasets. Information for this dataset is collected from trusted websites, local and international popular newspapers. This coronavirus dataset not only help to track the spreading route of coronavirus but also can be used for predicting the possible spreading route of similar future pandemics. This dataset consists of 186 countries' useful data related to COVID-19 pandemic from November 17, 2019, to May 16, 2020, with 8 unique variables that provide the information of the nature of the spread of COVID-19. The datasets mainly focus on two major fields, first one is First Case which consists of information of Date of First Case(s), Number of confirm Case(s) at First Day, Age of the patient(s) of First Case, Last Visited Country and the other one First Death information consist of Date of First Death and Age of the Patient who died first for every Country mentioning corresponding Continent.This dataset also can perform a bunch of predictions using Machine Learning applications, like -how fast the virus is spreading, affect rate, death rate, death rate and able to represent comparison between other pandemics. Using this dataset, any similar pandemic spreadness could be predicted earlier and necessary precaution measures could be taken.
| S-EPMC7430301 | biostudies-literature
Project description:Background:The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. Case presentation:Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient's condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. Conclusions:This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.
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| S-BSST563 | biostudies-other
Project description:BACKGROUND:Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION:A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION:COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.
| S-EPMC7146072 | biostudies-literature
Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
2020-12-11 | GSE163005 | GEO
Project description:IntroductionGuillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy that was reported following meningococcus, polio, influenza and rabies vaccines. However, an association with the COVID-19 vaccine is yet to be established.Presentation of caseWe present the case of an elderly gentleman with no history of SARS-CoV-2 infection or any recent viral or bacterial illnesses who presented with GBS 20 days after the second dose of COVID-19 vaccination. The diagnosis was established based on physical examination, magnetic resonance imaging (MRI) of the spine, cerebrospinal fluid (CSF) analysis and electromyography (EMG).DiscussionDue to the occurrence of GBS after certain types of infections, molecular mimicry has become widely acceptable as the underlying pathophysiology. The reported cases of GBS following vaccination further supported this theory, however proving a causal relationship between vaccines and GBS on the molecular level remains a challenge.ConclusionsTo the best of our knowledge this is the first reported case in the state of Qatar. It is important to mention that more research is needed to establish an association between COVID-19 vaccine and GBS. In our opinion, the benefits of COIVID-19 vaccine largely outweigh its risks.
| S-EPMC8253659 | biostudies-literature