Mesenchymal stem cell research progress for the treatment of COVID-19

At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.

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COVID-19. A review

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2020.1298 ◽

2020 ◽

Vol 90 (2) ◽

Cited By ~ 9

Author(s):

Irappa Madabhavi ◽

Malay Sarkar ◽

Nagaveni Kadakol

Keyword(s):

Distress Syndrome ◽

Case Fatality ◽

Genomic Analysis ◽

Multiple Organ ◽

Low Grade ◽

Epidemic Outbreak ◽

Wuhan City ◽

Novel Coronavirus ◽

The Universe ◽

Highly Virulent

The enduring epidemic outbreak which started in Wuhan city of China, in December 2019 caused by the 2019 novel coronavirus (COVID- 19) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a dangerous and deadly Public Health disaster of International apprehension, with cases confirmed in several countries. This novel community health trouble is frightening the universe with clinical, psychological, emotional, collapse of health system and economical slowdown in each and every part of the world infecting nearly 200 countries. A highly virulent and pathogenic COVID-19 viral infection with incubation period ranging from two to fourteen days, transmitted by breathing of infected droplets or contact with infected droplets, belongs to the genus Coronavirus with its high mutation rate in the Coronaviridae. The likely probable primary reservoir could be bats, because genomic analysis discovered that SARSCoV-2 is phylogenetically interrelated to SARS-like bat viruses. The transitional resource of origin and transfer to humans is not known, however, the rapidly developing pandemic has confirmed human to human transfer. Approximately 1,016,128 reported cases, 211,615 recovered cases and 53,069 deaths of COVID-2019 have been reported to date (April 2, 2020). The symptoms vary from asymptomatic, low grade pyrexia, dry cough, sore throat, breathlessness, tiredness, body aches, fatigue, myalgia, nausea, vomiting, diarrhea, to severe consolidation and pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction leading to death with case fatality rate ranging from 2 to 3%.

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Phenylbenzopyrone of flavonoids as a potential scaffold to prevent SARS-CoV-2 replication by inhibiting its MPRO main protease

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210127113027 ◽

2021 ◽

Vol 22 ◽

Author(s):

Angamba Meetei Potshangbam ◽

Potshangbam Nongdam ◽

A. Kiran Kumar ◽

R.S. Rathore

Keyword(s):

Antiviral Drugs ◽

Dynamics Simulation ◽

Compound Libraries ◽

Main Protease ◽

Enterovirus A71 ◽

Short Period ◽

Novel Coronavirus ◽

Effective Drugs ◽

Drug Leads ◽

Better Than

Background: In December 2019, an outbreak of a pneumonia-like illness, Coronavirusdisease-2019 (COVID-19), originating from Wuhan, China was linked to novel coronavirus, now termed SARS-CoV-2. Unfortunately, no effective drugs or vaccines have been reported yet. The main protease (MPRO) remains the most validated pharmacological target for the design and discovery of inhibitors. Objective: The purpose of the study was to find a prospective natural scaffold as an inhibitor for MPRO main protease in SARS-CoV-2 and compare it with repurposed antiviral drugs lopinavir and nelflinavir. Methods: Natural compound libraries were screened for potential scaffold against MPRO main protease. Molecular dynamics simulation, MM-GBSA and principle component analyses of enzyme-ligand complexes were carried out with the top-ranking hits and compared with the repurposed antiviral drugs lopinavir and nelfinavir. Results: The structure-based virtual screening indicated phenylbenzopyrone of flavonoids as one of the top-ranking scaffolds that have the potential to inhibit the main protease with O-glycosidic form performing better than corresponding aglyconic form. Simulation studies indicated that glycosidic form of flavonoid as more suitable inhibitor with compounds rutin, procyanidin B6, baicalin and galloylquercetin, demonstrating high affinity and stability, and rutin emerging as one of the best candidate compound. Interestingly, rutin was reported to have inhibitory activity against similar protease (3Cprotease of enterovirus A71) as well as implicated in lung fibrosis. Conclusion: The present study displaying flavonoids, possessing a potential scaffold for inhibiting main protease activity for all betacoronavirus is an attempt to provide new and safe drug leads within a reasonably short period.

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COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa114 ◽

2020 ◽

Vol 75 (7) ◽

pp. 1667-1670 ◽

Cited By ~ 203

Author(s):

Dan Zhou ◽

Sheng-Ming Dai ◽

Qiang Tong

Keyword(s):

T Cell Activation ◽

Cell Activation ◽

Distress Syndrome ◽

Antiviral Effect ◽

Inhibitory Effect ◽

Clinical Use ◽

Cytokine Release ◽

Novel Coronavirus ◽

Effective Drugs ◽

Preventive Effects

Abstract A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide. The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release. There is an urgent need to identify safe and effective drugs for treatment. Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation. It has a safer clinical profile and is suitable for those who are pregnant. It is cheaper and more readily available in China. We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression.

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POTENTIAL THERAPIES FOR TREATMENT OF COVID-19

Revista de Ciência Veterinária e Saúde Pública ◽

10.4025/revcivet.v7i1.55502 ◽

2020 ◽

Vol 7 (1) ◽

pp. 062-071

Author(s):

Beatriz Gasser ◽

Ricardo Andres Ramirez Uscategui

Keyword(s):

Clinical Trials ◽

Distress Syndrome ◽

Multiple Organ ◽

The Novel ◽

Controlled Clinical Trials ◽

Interferon Β ◽

The World ◽

Novel Coronavirus ◽

Time Point

Since discovery of the novel coronavirus (SARS-CoV-2) in December of 2019, this viral pneumonia originated in Wuhan, China quickly spread around the world. This new disease, called COVID-19 can cause Acute Respiratory Distress Syndrome (ARDS) due to an uncontrolled inflammatory response like sepsis, that leads to multiple organ failure and even death. Several pharmacotherapeutics alternatives are being tested over the world, looking for most diverse drugs that might be able to fight the infection. The objective of this paper is to review the main pharmacotherapeutics techniques development, as remdesivir, chloroquine/hydroxychloroquine, lopinavir plus ritonavir, interferon-β, ivermectin, anticoagulants, convalescent plasma and vaccine, currently undergoing clinical trials in order to evaluate its effectiveness and safety to combat the COVID-19, presenting their characteristics, possible adverse effects and main scientific findings of its potential action. In conclusion, some therapies presented promising in-vitro results or in the treatment of some patients, nonetheless, multicentric blinded placebo controlled clinical trials are necessary to determine their effectiveness, safety, dosage, and best time point of treatment.

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COVID-19 and Cytokine Storm

Forbes Journal of Medicine ◽

10.5222/forbes.2020.79188 ◽

2020 ◽

Author(s):

Mustafa Kurtuluş ◽

İbrahim Pirim

Keyword(s):

Immune Response ◽

Host Response ◽

Distress Syndrome ◽

Multiple Organ ◽

Past Century ◽

Viral Agent ◽

Disease Course ◽

Cytokine Storm ◽

The Past ◽

Novel Coronavirus

Although the etiopathogenesis of infections has been largely illuminated by technical and scientific developments in the past century; many issues are still not clear today. The word “there is no disease, there is a patient” is stil valid today. Because the immune response of the host is as important as the virulence of the pathogen in infections and disease course can vary a lot according to the person. Cytokine Storm is seen exactly in a group of diseases where the host response is very prominent. For this reason, Cytokine Storm Syndrome (CSS) is mostly mentioned. CSS emerging due to different inflammatory etiologies; it is an overwhelming systemic inflammation, hemodynamic imbalance, multiple organ failure, and potentially leading to death. After being first seen in Influenza in 2003 as a viral agent, CSS was seen in SARS-Cov, MERS-CoV and SARS-CoV2, which were found to be the las thuman disease from the Corona viridea family.The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. Uncontrolled production of pro-inﬂammatory mediators contributes to, acut respiratory distress syndrome (ARDS) and cytokine storm syndrome in COVID-19.

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Immunomodulation and Regenerative Capacity of MSCs for Long-COVID

International Journal of Molecular Sciences ◽

10.3390/ijms222212421 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12421

Author(s):

Xin Ya Loke ◽

Siti A. M. Imran ◽

Gee Jun Tye ◽

Wan Safwani Wan Kamarul Zaman ◽

Fazlina Nordin

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Distress Syndrome ◽

Regenerative Therapy ◽

Cytokine Storm ◽

Regenerative Capacity ◽

Lung Injuries ◽

Severity Of The Disease ◽

Effective Drugs ◽

Future Utilization

The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.

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Pathogenesis, Diagnosis, and Treatment of Hemostatic Disorders in COVID-19 Patients

Acta Naturae ◽

10.32607/actanaturae.11182 ◽

2021 ◽

Vol 13 (2) ◽

pp. 79-84

Author(s):

Airat F. Khalirakhmanov ◽

Kamilla F. Idrisova ◽

Raushaniya F. Gajfullina ◽

Sergey V. Zinchenko ◽

Rustem I. Litvinov ◽

...

Keyword(s):

Multiple Organ ◽

Pulmonary Insufficiency ◽

The Novel ◽

Thromboembolic Complications ◽

Short Period ◽

Prevention And Treatment ◽

Organ Failures ◽

Coronavirus Infection ◽

Novel Coronavirus ◽

Hemostatic Disorders

The novel coronavirus infection named COVID-19 was first detected in Wuhan, China, in December 2019, and it has been responsible for significant morbidity and mortality in scores of countries. At the time this article was being written, the number of infected and deceased patients continued to grow worldwide. Most patients with severe forms of the disease suffer from pneumonia and pulmonary insufficiency; in many cases, the disease is generalized and causes multiple organ failures and a dysfunction of physiological systems. One of the most serious and prognostically ominous complications from COVID-19 is coagulopathy, in particular, decompensated hypercoagulability with the risk of developing disseminated intravascular coagulation. In most cases, local and diffuse macro- and microthromboses are present, a condition which causes multiple-organ failure and thromboembolic complications. The causes and pathogenic mechanisms of coagulopathy in COVID-19 remain largely unclear, but they are associated with systemic inflammation, including the so-called cytokine storm. Despite the relatively short period of the ongoing pandemic, laboratory signs of serious hemostatic disorders have been identified and measures for specific prevention and correction of thrombosis have been developed. This review discusses the causes of COVID-19 coagulopathies and the associated complications, as well as possible approaches to their early diagnosis, prevention, and treatment.

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Severe Acute Respiratory Coronavirus-2: A Critical Review of Virus Biology, Genome and Pathophysiology

The Open Dentistry Journal ◽

10.2174/1874210602115010286 ◽

2021 ◽

Vol 15 (1) ◽

pp. 286-295

Author(s):

Akhilesh Agrawal ◽

Supriya Kashikar ◽

kaivalya Deo ◽

Abhay Gaidhane ◽

Anand Bansod ◽

...

Keyword(s):

Distress Syndrome ◽

Cell Interaction ◽

Multiple Organ ◽

High Rate ◽

Current Review ◽

The World ◽

Novel Coronavirus ◽

Respiratory Coronavirus ◽

Host Cell Interaction ◽

Genomic Organisation

Severe Acute Respiratory Coronavirus-2 [SARS-CoV-2] emerged as a great threat to the world at the end of December 2019 in China. The SARS-CoV-2 evolved from a virus responsible for the SARS epidemic in 2002. The SARS-CoV-2 has a high rate of human-human transmission and originated from the bat. It has a close resemblance with bat-like-SARS-CoV compared to SARS-CoV; however, the Spike protein responsible for virus-host cell interaction possesses the least similarity with that of SARS-CoV. Cytokine Storm is associated with the severity of Covid-19 and leads to acute respiratory distress syndrome [ARDS] and/or multiple organ dysfunction syndromes [MODS]. In the current review article, the features of a novel coronavirus, including viral biology, genomic organisation, life cycle, pathophysiology and genetic diversity, have been discussed. The development of policies and plans which can prepare the world for future pandemics has also been proposed. In addition, the drug development pipelines, diagnostic facilities and management of such pandemics need an up-gradation to contain the current as well as future outbreaks.

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Responding to the COVID-19 pandemic in Ghana

Ghana Medical Journal ◽

10.4314/gmj.v54i2.1 ◽

2020 ◽

Vol 54 (2) ◽

pp. 72-73

Author(s):

Ernest Kenu ◽

Joseph Frimpong ◽

Kwadwo Koram

Keyword(s):

Respiratory Distress ◽

Distress Syndrome ◽

Rna Virus ◽

Respiratory Illness ◽

The United States ◽

World Health ◽

Infected Person ◽

Wuhan City ◽

Novel Coronavirus ◽

Health Organization

On 12 January 2020, the World Health Organization (WHO) confirmed that a novel coronavirus was the cause of a respiratory illness in a cluster of people in Wuhan City, Hubei Province, China. The disease was christened COVID-19 and the pathogen (an RNA virus) identified as SARS-Coronavirus-2 (SARS-CoV-2).1,2 The virus is primarily spread through contact with small droplets produced from coughing, sneezing, or talking by an infected person. While a substantial proportion of infected individuals may remain asymptomatic, the most common symptoms in clinical cases include, fever, cough, acute respiratory distress, fatigue, and failure to resolve over 3 to 5 days of antibiotic treatment. Complications may include pneumonia and acute respiratory distress syndrome.3 Over five million confirmed cases of COVID-19 has been recorded globally with more than 300,000 deaths as at 25th May 2020. The United States of America has recorded the highest number of cases with more than 1.5 million and over 100,000 deaths.4 In Africa, more than 90,0000 cases have been reported with about 3,000 deaths. South Africa has recorded the highest number of cases with 23,615 cases and 481 deaths. Ghana confirmed its first cases of COVID-19 on 12th March 2020 and had as at 25 May 2020 recorded over 7,000 cases with 34 deaths.5

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OUTBREAK, EPIDEMIOLOGY, THERAPEUTICS AND PREVENTION OF CORONAVIRUS DISEASE-2019: A REVIEW

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i5.39755 ◽

2020 ◽

pp. 1-4

Author(s):

ZULFKAR LATIEF QADRIE ◽

SHAHID UD DIN WANI ◽

SURYA PRAKASH GAUTAM ◽

M. KHALID AHMED KHAN

Keyword(s):

Public Health ◽

The Other ◽

Short Report ◽

Sudden Increase ◽

Wuhan City ◽

Health Measures ◽

Patient Diagnosis ◽

Short Period ◽

Novel Coronavirus ◽

Positive Results

The outbreak of pneumonia of unknown cause during December 2019 was reported from Wuhan City, Hubei province capital in China as its epicenter. Symptoms of pneumonia in several patients admitted to hospitals from Wuhan, China during December 2019. The sudden increase in the patients having the same symptoms, in due course the contributing means was isolated from the infected populace. In the present short report, we have summarized various public health measures, viz., early marking of the suspected patient, diagnosis, and supervision of the suspected cases that will help prevent Coronavirus disease in 2019. At the start, it was named as the 2019 novel coronavirus (2019-nCoV), and later it has been named Coronavirus disease 2019 (COVID-19) recently. Within a few weeks of a short period, the virus affected the other of China after Wuhan and later in two to three months, it is present in more than 140 countries around the globe and adding. As of 03rd August 2020, there have been 17.6 million established cases worldwide, and 680, 894 deaths have been documented, with 11,460,074 recovered. Worldwide, multiple trails are going on with the hope to find the treatment and some have positive results. On the other hand, because no vaccine is offered, the precautionary methods are the best way to fight the virus.

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