Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19

Jeyaraman, Madhan; John, Albin; Koshy, Santosh; Ranjan, Rajni; Anudeep, Talagavadi Channaiah; Jain, Rashmi; Kumari, Swati; Jha, Niraj Kumar; Sharma, Ankur; Kesari, Kavindra Kumar; Prakash, Anand; Nand, Parma; Jha, Saurabh; Reddy, P. Hemachandra

doi:10.1016/j.bbadis.2020.166014

Cited by 33 publications

(25 citation statements)

References 80 publications

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“…Possessing strong immunomodulatory and regenerative activities, MSCs are considered promising candidates to treat or ameliorate the severity of SARS-CoV-2 in patients with COVID-19, lessen ARDS and halt cytokine storm, improve pulmonary function, and reduce morbidity and mortality. Recent clinical trials proved these to be safe and efficacious in reducing overall outcome of the disease, though few limitations and challenges need to be addressed for their full practical utility during pandemic as well to have high value as a next-generation therapy and to counter future challenges [ 141 , 143 , 144 , 145 , 146 , 147 ].…”

Section: Regulation Of Pro- and Anti-inflammatory Cytokines Via Immunmentioning

confidence: 99%

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

et al. 2021

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.

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Section: Regulation Of Pro- and Anti-inflammatory Cytokines Via Immunmentioning

confidence: 99%

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

et al. 2021

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“…Sustained inflammation can lead to cell destruction and apoptosis. SARS-CoV-2 can cause hyper inflammation, and in an elderly person prone to an over-stimulated inflammatory response, this combination can make them more susceptible to death by “cytokine storm” and offers a possible explanation for the increased mortality among the elderly population (Jeyaraman et al, 2020 ).…”

Section: Mitochondria and Agingmentioning

confidence: 99%

Impact of COVID-19 on Mitochondrial-Based Immunity in Aging and Age-Related Diseases

Ganji

Reddy

2021

Front. Aging Neurosci.

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The coronavirus disease 2019 (COVID-19) has become a deadly pandemic with surging mortality rates and no cure. COVID-19 is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) with a range of clinical symptoms, including cough, fever, chills, headache, shortness of breath, difficulty breathing, muscle pain, and a loss of smell or taste. Aged individuals with compromised immunity are highly susceptible to COVID-19 and the likelihood of mortality increases with age and the presence of comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, or chronic obstructive pulmonary disease. Emerging evidence suggests that COVID-19 highjacks mitochondria of immune cells, replicates within mitochondrial structures, and impairs mitochondrial dynamics leading to cell death. Mitochondria are the powerhouses of the cell and are largely involved in maintaining cell immunity, homeostasis, and cell survival/death. Increasing evidence suggests that mitochondria from COVID-19 infected cells are highly vulnerable, and vulnerability increases with age. The purpose of our article is to summarize the role of various age-related comorbidities such as diabetes, obesity, and neurological diseases in increasing mortality rates amongst the elderly with COVID-19. Our article also highlights the interaction between coronavirus and mitochondrial dynamics in immune cells. We also highlight the current treatments, lifestyles, and safety measures that can help protect against COVID-19. Further research is urgently needed to understand the molecular mechanisms between the mitochondrial virus and disease progression in COVID-19 patients.

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“…Further research is also needed to develop specific treatment strategies for men with an impaired male reproductive system resulting from SARS-CoV-2 infection. In this regard, several therapeutic methods have been developed recently for the treatment of COVID-19 patients, such as mesenchymal stem cells [ 104 ], miRNA-based therapy (responsible for changing ACE-2 expression) [ 105 ] and hormone therapy [ 106 ]. Therefore, treatment regimens should also consider the androgen levels of men, as SARS-CoV-2 infection is believed to be associated with androgen secretion [ 9 ].…”

Section: Future Perspectivementioning

confidence: 99%

Viral pathogenesis of SARS-CoV-2 infection and male reproductive health

et al. 2021

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Coronavirus disease 2019 (COVID-19) has emerged as a new public health crisis, threatening almost all aspects of human life. Originating in bats, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans through unknown intermediate hosts, where it is primarily known to cause pneumonia-like complications in the respiratory system. Organ-to-organ transmission has not been ruled out, thereby raising the possibility of the impact of SARS-CoV-2 infection on multiple organ systems. The male reproductive system has been hypothesized to be a potential target of SARS-CoV-2 infection, which is supported by some preliminary evidence. This may pose a global threat to male fertility potential, as men are more prone to SARS-CoV-2 infection than women, especially those of reproductive age. Preliminary reports have also indicated the possibility of sexual transmission of SARS-CoV-2. It may cause severe complications in infected couples. This review focuses on the pathophysiology of potential SARS-CoV-2 infection in the reproductive organs of males along with their invasion mechanisms. The risks of COVID-19 on male fertility as well as the differences in vulnerability to SARS-CoV-2 infection compared with females have also been highlighted.

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Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19

Cited by 33 publications

References 80 publications

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

Impact of COVID-19 on Mitochondrial-Based Immunity in Aging and Age-Related Diseases

Viral pathogenesis of SARS-CoV-2 infection and male reproductive health

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