C-Reactive Protein (CRP): A Potent Inflammation Biomarker in Psychiatric Disorders.

An increasing number of studies have investigated the role of inflammation in psychiatric disorders, by demonstrating how an altered/dysfunctional immunological and inflammatory system may underpin a psychiatric condition. Particularly, several studies specifically investigated the role of a neuroinflammatory biomarker, named C-reactive protein (CRP), in psychiatric disorders. Overall, even though scientific literature so far published still does not appear definitive, CRP is more likely reported to be elevated in several psychiatric disorders, including schizophrenia, mood disorders, anxiety disorders and post-traumatic stress disorder. Moreover, a low-grade inflammation (CRP >3 mg/L) has been more likely observed in a subgroup of patients affected with a more severe psychopathological symptomatology, more treatment resistance and worst clinical mental illness course, strengthening the hypothesis of the need for a different clinical and prognostic characterization based on this concomitant neuroinflammatory predisposition. However, even though further research studies are needed to confirm this preliminary evidence, CRP may represent a potential clinical routine biomarker which could be integrated in the clinical routine practice to better characterize clinical picture and course as well as address clinicians towards a personalized treatment.

Symbiotic microbiota: A class of potent immunomodulators

Microbiome is known to exist as symbiotic commensals in humans, domestic and wild animals, birds, fishes, reptiles, insects etc. DNA sequencing and metagenomic platforms have deciphered the complex role played by communities of microbiota (bacteria, fungi, viruses, protozoa and other eukaryotic species) in survival and regulation of host physiology, metabolism and regulation of host immune system. Any alteration in the microbial population or breach in the symbiotic alliance with the host may ultimately lead to development of different kinds of pathologies. Realization of the enormous role played by the microbiome in health and diseases of human and domestic livestock led researchers to find ways to modulate these resident microbiomes for improvement in health and management of diseases. Theoretically there are several ways that can be employed for manipulating the composition and functional capacity of the resident microbiome, which may lead to improvements in human and livestock health. Though studies have shown therapeutic potential of the microbiome, considerable challenges exist in the actual implementation of these strategies in clinical settings. This review discusses the symbiotic relationship between microbiome and host and strategies to modulate host immune responses by manipulating microbiome profile. Paper also highlights how to overcome existing obstacles for successful implementation of microbiome manipulation techniques. In this era of COVID-19, it would be worth analysing the role of resident microbiome in the magnitude of COVID-19 severity which may have occurred through immunomodulation.

Virology of SARS-CoV-2 and management of nCOVID-19 utilizing immunomodulation properties of human mesenchymal stem cells-a literature review.

OBJECTIVE: The objective of this review article is to outline the pathology, virology and mechanism of severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) and to study the regenerative role of mesenchymal stem cells (MSCs) to tackle the lung damage caused by SARS-CoV-2. BACKGROUND: The MSCs possess trophic potentialities which enable them to find out the sites of injury or inflammation and because of their pleiotropic and pericytic nature, these cells are capable of differentiating into different cell types. The MSCs can be derived from a variety of tissue sources be it adult or embryonic origin. The one major characteristic of MSCs is that they are immunologically naïve in terms of expression of MHC Class II. This very low or no expression of MHC class II makes them useful in clinical settings where they can be used in allogenic transplant cases. This allogenic transplant possibilities of these MSCs makes them one of the most researched stem cells and investigated for cell-based therapies. Though these MSCs are in clinical settings for long the one even more important characteristic which makes them even more in demand is their immunomodulatory properties which have been used in various cases to mitigate the effect of overstimulation of the immune system. In recent times after the pandemic of the novel corona virus disease 2019 (nCOVID-19) generated by SARS-CoV-2, the effect of various MSCs isolated from various tissue sources are being utilized to curb the overstimulation of immune response, so that the immune system can be brought under some regulation to ultimately reduce the effect of inflammation. METHODS: In this review article, we have reviewed the existing literature, data and ongoing clinical trials by using keywords like novel coronavirus, COVID-19, SARS-CoV-2, MERS-CoV, acute respiratory distress syndrome, mesenchymal stem cells, immunomodulation properties of stem cells, regenerative properties of stem cells, cell therapy, clinical trials of stem cells, clinical trials of COVID-19 and stem cells till 20th August 2020 using database named PubMed, NCBI, Google Scholar, Scopus, Research Gate and Clinicaltrials.gov. CONCLUSIONS: Thus, concluding the therapeutic potential of MSCs in managing and treating COVID-19.

Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.

OBJECTIVE: In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients. METHODS: A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) - Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days. RESULTS: There was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395-3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18-3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25-0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4 + and CD8 + T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups. CONCLUSION: As these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.

Recent Advances in Biomedical, Therapeutic and Pharmaceutical Applications of Microbial Surfactants.

The spread of antimicrobial-resistant pathogens typically existing in biofilm formation and the recent COVID-19 pandemic, although unrelated phenomena, have demonstrated the urgent need for methods to combat such increasing threats. New avenues of research for natural molecules with desirable properties to alleviate this situation have, therefore, been expanding. Biosurfactants comprise a group of unique and varied amphiphilic molecules of microbial origin capable of interacting with lipidic membranes/components of microorganisms and altering their physicochemical properties. These features have encouraged closer investigations of these microbial metabolites as new pharmaceutics with potential applications in clinical, hygiene and therapeutic fields. Mounting evidence has indicated that biosurfactants have antimicrobial, antibiofilm, antiviral, immunomodulatory and antiproliferative activities that are exploitable in new anticancer treatments and wound healing applications. Some biosurfactants have already been approved for use in clinical, food and environmental fields, while others are currently under investigation and development as antimicrobials or adjuvants to antibiotics for microbial suppression and biofilm eradication strategies. Moreover, due to the COVID-19 pandemic, biosurfactants are now being explored as an alternative to current products or procedures for effective cleaning and handwash formulations, antiviral plastic and fabric surface coating agents for shields and masks. In addition, biosurfactants have shown promise as drug delivery systems and in the medicinal relief of symptoms associated with SARS-CoV-2 acute respiratory distress syndrome.

Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits.

Introduction: COVID-19 pandemic has caused huge loss of human lives and extensive socio-economic damages. The immuno-pathology of this disease is neither clearly understood nor there are effective drugs for severe cases of COVID-19. Repurposing of available drugs for the treatment of COVID-19 is imperative.Areas Covered: This review has gathered the evidence from PubMed, Google Scholar, WHO, and other reliable websites on COVID-19 and summarized the existing knowledge of the immuno-pathology of COVID-19. We elucidated how vitamin D through its diverse actions on immune effector cells, epithelial cells, or renin-angiotensin-aldosterone system could have a modulatory role on the pathogenic mechanisms of COVID-19. The epidemiological evidence associating vitamin D deficiency with the severity and incidence of COVID-19 is also presented. However, the evidence of clinical benefit to patients of COVID-19 from randomized controlled trials with vitamin D has not come as yet.Expert opinion: It is now established that fatality of COVID-19 is primarily determined by hyperactivation of the host's innate immune system in response to SARS-CoV-2 invasion, and thus the research on the immuno-modulatory and other roles of vitamin D against viral infections should be pursued vigorously. This would be also useful for future pandemics caused by other novel viruses.

Perspectives About Modulating Host Immune System in Targeting SARS-CoV-2 in India.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus induced disease-2019 (COVID-19), is a type of common cold virus responsible for a global pandemic which requires immediate measures for its containment. India has the world's largest population aged between 10 and 40 years. At the same time, India has a large number of individuals with diabetes, hypertension and kidney diseases, who are at a high risk of developing COVID-19. A vaccine against the SARS-CoV-2, may offer immediate protection from the causative agent of COVID-19, however, the protective memory may be short-lived. Even if vaccination is broadly successful in the world, India has a large and diverse population with over one-third being below the poverty line. Therefore, the success of a vaccine, even when one becomes available, is uncertain, making it necessary to focus on alternate approaches of tackling the disease. In this review, we discuss the differences in COVID-19 death/infection ratio between urban and rural India; and the probable role of the immune system, co-morbidities and associated nutritional status in dictating the death rate of COVID-19 patients in rural and urban India. Also, we focus on strategies for developing masks, vaccines, diagnostics and the role of drugs targeting host-virus protein-protein interactions in enhancing host immunity. We also discuss India's strengths including the resources of medicinal plants, good food habits and the role of information technology in combating COVID-19. We focus on the Government of India's measures and strategies for creating awareness in the containment of COVID-19 infection across the country.

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19.

The recent pandemic situation transpired due to coronavirus novel strain SARS-CoV-2 has become a global concern. This human coronavirus (HCov-19) has put the world on high alert as the numbers of confirmed cases are continuously increasing. The world is now fighting against this deadly virus and is leaving no stone unturned to find effective treatments through testing of various available drugs, including those effective against flu, malaria, etc. With an urgent need for the development of potential strategies, two recent studies from China using Mesenchymal Stem Cells (MSCs) to treat COVID-19 pneumonia have shed some light on a potential cure for the COVID-19 infected patients. However, MSCs, despite being used in various other clinical trials have always been questioned for their tendency to aggregate or form clumps in the injured or disease microenvironment. It has also been reported in various studies that exosomes secreted by these MSCs, contribute towards the cell's biological and therapeutic efficacy. There have been reports evaluating the safety and feasibility of these exosomes in various lung diseases, thereby proposing them as a cell-free therapeutic agent. Also, attractive features like cell targeting, low-immunogenicity, safety, and high biocompatibility distinguish these exosomes from other synthetic nano-vesicles and thus potentiate their role as a drug delivery nano-platform. Building upon these observations, herein, efforts are made to give an overview of stem cell-derived exosomes as an appealing therapeutic agent and drug delivery nano-carrier. In this review, we briefly recapitulate the recent evidence and developments in understanding exosomes as a promising candidate for novel nano-intervention in the current pandemic scenario. Furthermore, this review will highlight and discuss mechanistic role of exosomes to combat severe lung pathological conditions. We have also attempted to dwell into the nano-formulation of exosomes for its better applicability, storage, and stability thereby conferring them as off the shelf therapeutic.