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      Stem cell therapy for COVID‐19, ARDS and pulmonary fibrosis

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          Abstract

          Coronavirus disease 2019 (COVID‐19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 mainly causes damage to the lung, as well as other organs and systems such as the hearts, the immune system and so on. Although the pathogenesis of COVID‐19 has been fully elucidated, there is no specific therapy for the disease at present, and most treatments are limited to supportive care. Stem cell therapy may be a potential treatment for refractory and unmanageable pulmonary illnesses, which has shown some promising results in preclinical studies. In this review, we systematically summarize the pathogenic progression and potential mechanisms underlying stem cell therapy in COVID‐19, and registered COVID‐19 clinical trials. Of all the stem cell therapies touted for COVID‐19 treatment, mesenchymal stem cells (MSCs) or MSC‐like derivatives have been the most promising in preclinical studies and clinical trials so far. MSCs have been suggested to ameliorate the cytokine release syndrome (CRS) and protect alveolar epithelial cells by secreting many kinds of factors, demonstrating safety and possible efficacy in COVID‐19 patients with acute respiratory distress syndrome (ARDS). However, considering the consistency and uniformity of stem cell quality cannot be quantified nor guaranteed at this point, more work remains to be done in the future.

          Abstract

          The potential mechanisms of MSCs therapy for COVID‐19. MSCs have great therapeutic potential in immunomodulation and tissue repair through secretion of soluble paracrine protein factors and exosomes. MSCs can regulate the functions of a variety of immune cells, secrete several cytokines, promote tissue repair and regeneration, and may play important therapeutic roles in patients with COVID‐19. MSCs: mesenchymal stem cells; HGF, hepatocyte growth factor; VEGF, vascular endothelial growth factor; KGF, keratinocyte growth factor; FGF, fibroblast growth factor; TGF‐β, transforming growth factor‐β; TNF‐α, tumor necrosis factor‐α; MSC‐exo, exosomes.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Fei Zhou, Ting Yu, Ronghui Du … (2020)
            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
              Article 0 comments Cited 10102 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yuanqing Tan: haojie@ioz.ac.cn , wuxf@ioz.ac.cn , 357769970@qq.com
                Jun Wu: haojie@ioz.ac.cn , wuxf@ioz.ac.cn , 357769970@qq.com
                Jie Hao:
                ORCID: https://orcid.org/0000-0002-7739-1850
                haojie@ioz.ac.cn
                Journal
                Journal ID (nlm-ta): Cell Prolif
                Journal ID (iso-abbrev): Cell Prolif
                Journal ID (doi): 10.1111/(ISSN)1365-2184
                Journal ID (publisher-id): CPR
                Title: Cell Proliferation
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0960-7722
                ISSN (Electronic): 1365-2184
                Publication date (Electronic): 24 October 2020
                Electronic Location Identifier: e12939
                Affiliations
                [ 1 ] Institute of Zoology State Key Laboratory of Stem Cell and Reproductive Biology Chinese Academy of Sciences Beijing China
                [ 2 ] Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing China
                [ 3 ] National Stem Cell Resource Center Chinese Academy of Sciences Beijing China
                [ 4 ] University of Chinese Academy of Sciences Beijing China
                Author notes
                [*] [* ] Correspondence

                Jie Hao, Jun Wu and Yuanqing Tan, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Chinese Academy of Sciences, Beijing, China.

                Emails: haojie@ 123456ioz.ac.cn ; wuxf@ 123456ioz.ac.cn ; 357769970@ 123456qq.com

                Author information
                https://orcid.org/0000-0002-5466-0819
                https://orcid.org/0000-0002-7739-1850
                Article
                Publisher ID: CPR12939
                DOI: 10.1111/cpr.12939
                PMC ID: 7645923
                PubMed ID: 33098357
                SO-VID: b96c2e37-5c7a-442c-b248-b2250017a47e
                Copyright © © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 September 2020
                Date revision received : 05 October 2020
                Date accepted : 06 October 2020
                Page count
                Figures: 4, Tables: 1, Pages: 15, Words: 25484
                Funding
                Funded by: International Partnership Program of Chinese Academy of Sciences
                Award ID: 152111KYSB20160004
                Funded by: the Key Research Projects of the Frontier Science of the Chinese Academy of Sciences
                Award ID: QYZDY‐SSW‐SMC002
                Funded by: National Key Research and Development Program
                Award ID: 2016YFA0101502
                Award ID: 2017YFA0104403
                Award ID: 2017YFA0105000
                Award ID: 2018YFA0108400
                Award ID: 2020YFC0843900
                Funded by: the Strategic Priority Research Program of the Chinese Academy of Sciences
                Award ID: XDA16030601
                Award ID: XDA16040502
                Funded by: the National Natural Science Foundation of China
                Award ID: 31621004
                Funded by: Beijing Municipal Science & Technology Commission
                Award ID: Z181100003818005
                Categories
                Subject: Review
                Subject: Reviews
                Custom metadata
                source-schema-version-number 2.0
                edited-state corrected-proof
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:06.11.2020

                ScienceOpen disciplines: Cell biology
                Keywords: clinical trials,covid‐19,mesenchymal stem cells,stem cell therapy
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: clinical trials, covid‐19, mesenchymal stem cells, stem cell therapy

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