Immunological Response of the Respiratory Tract in the SARS-CoV-2 Infection

Severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) is a contagious pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. The pathogenesis and immunological responses of SARS-CoV-2 infection are poorly understood until now. Once a person gets infected by SARS-COV-2, both innate and adaptive immunity gets compromised, which further plays an important role in making the disease more severe. The host's innate immune system forms the first layer of defense for protection from viral infections and initiates activation of the adaptive immune system in order to give maximum protection. The respiratory tract maintains the balance of T cell, B cell pro-and anti-inflammatory responses in order to protect the tissue from damage and diseases. In this review, the current updates related to the involvement of the immune system in the antiviral defense against SARS-CoV-2 have been discussed. These novel insights within the immunological response in the respiratory tract would support the future development of vaccines and immunoregulatory therapy for SARS-CoV-2 infection.Copyright © 2021 Bentham Science Publishers.

CD4 + Count: a Variable to Be Considered to Prioritize COVID-19 Vaccination in PLHIV.

The outbreak of the COVID-19 propagates, pressurizing the healthcare system by emphasizing and worsening the inequities. While many vaccines have shown excellent efficacy in protecting the general public from the COVID-19 infection, the efficacy of these vaccines for people living with HIV (PLHIV), especially those having a different range of CD4 + T-cell, has yet to be thoroughly investigated. Few studies have uncovered the escalated infection and death rates due to the COVID-19 infection in individuals with low CD4 + T-cells. Additionally, PLHIV has a low CD4 + count; furthermore, specific CD4 + T cells for coronavirus have a vigorous Th1 role and are related to the protective antibody responses. Follicular helper T cells (TFH) are vulnerable to HIV and virus-specific CD4 & CD8 T-cells which are essential for viral infection clearance and defective immune responses which further contributes to the development of illness. The specific CD8 & CD4 + T-cell reaction to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in almost all COVID-19 recovered individuals, which is related to the size of antibodies of immunoglobulin G. It has previously been demonstrated that PLHIV has decreased responses to certain vaccines and that these responses are reliant on CD4 + T-cell levels. COVID-19 vaccines will likely have a lower response or limited effect, in PLHIV having low CD4 + T-cells.

Mucormycosis: A triple burden in patients with diabetes during COVID-19 Pandemic.

With the upsurge in the cases of COVID-19 around the world, plenty of potential COVID-19 complications are becoming more prevalent, including a higher risk of secondary bacterial and fungal infections. Mucormycosis is one such condition which has high prevalence among individuals with diabetes who were infected with COVID-19.The usage of steroids in the treatment further inflates the risk of infection and exacerbation of disease in pre-existent mucormycosis patients. Generally, Corticosteroid-induced diabetes can arise on long-term steroid medication, increasing the likelihood of mucormycosis. In patients with COVID-19, the indications and dose of corticosteroids should be properly regulated, and persons with diabetes who take insulin or oral anti-diabetic medicines should be cautious. To avoid poor outcomes, strategies to improve glycemic management should be emphasized. This narrative review elucidates different disciplines on rampant use of steroids, iron and zinc supplements as well as the methods utilized as primary or adjunctive treatment of this fatal condition. This article may help to pave the way for robust research that needs to be done to tackle the deadly triple burden of the disease.

Nutritional Aspects of People Living with HIV (PLHIV) Amidst COVID-19 Pandemic: an Insight

Purpose of Review This review elaborates the role of malnutrition in PLHIV (people living with HIV) in the context of COVID-19 and emphasis the need of supplementation, dietary intervention, and nutritional counselling in the post-COVID era. One of the most critical challenges among HIV/AIDS patients is malnutrition since it weakens the immune system and increases risk to opportunistic infections. In HIV (human immunodeficiency virus) infection, weight loss is prevalent due to reduced nutritional consumption, malabsorption, abnormal metabolism, and antiretroviral therapy. Sufficient nutrition is required for optimal immune function, as a result, food therapy is now considered an important adjuvant in the treatment of HIV patients. Recent Findings Nutritional intervention, such as the use of dietary supplements, can help to prevent nutrient deficiency, lowering the death risk among malnourished HIV population. Immunocompromised individuals are at very high risk for COVID-19 and malnutrition increases the risk of infection by multiple folds. Interventions, such as nutrition education and counselling are important, to improve the condition of HIV Patients by optimising their nutritional status. Summary A balanced diet should be one of the most important priorities in preventing PLHIV against the potentially deadly consequences of COVID-19. It is to be ensured that HIV-positive persons continue to get enough and appropriate assistance, such as nutrition and psychological counselling, in the context of COVID-19 infection. The use of telemedicine to maintain nutritional intervention can be beneficial. To meet their nutritional needs and minimise future difficulties, PLHIV infected with COVID-19 should get specialised nutritional education and counselling. Graphical

Ayurveda: The Prominence of Herbal Medicine in Containment of COVID-19

The global community is in a vulnerable and intricate state due to the COVID-19 pandemic given the lack of targeted drugs and extreme population making it an arduous journey to the public system of health care towards the extermination of the disease. The essentiality of newer compounds, novel medical instruments, and practices for diagnosis, cure, and prevention of the COVID-19 infection is the greatest concern. Since the persistent waves of COVID-19 are being observed at a variety of location across the globe, and the intensity and mutation of the virus is still possessing an inviolable threat to humanity. Along with conventional medicine, the application of traditional medicine practices using natural and herbal products has been proved effective in several disease conditions. The usage of Traditional Chinese medicine and ayurvedic medicine is used to treat COVID-19 infected patients in China and India respectively marks the contribution and effectiveness of traditional medical therapy in the restriction of the virus. The prominence of herbal products for prophylactic and symptomatic treatment for COVID-19 is notable and recommended by various organizations and governments in the world. All the pragmatic considerations and evidence to use ayurvedic practices on a large scale require further animal and robust human studies. This article reviews various practices, herbal products, effectiveness, case studies and the contribution of ayurvedic medicine, to be used to treat and restrict the viral epidemic and may further provide a forward insight into future learning, evidence compiling, and research in the respective domain.

Impact of COVID-19 on Antimicrobial Resistance in Paediatric Population: a Narrative Review.

Purpose of Review: Irrational use of antimicrobials has been reported in paediatric population during the COVID-19 time period. This may lead to potential development of antimicrobial resistance and increased morbidity and mortality among this vulnerable population. The purpose of this review is to ascertain the impact of COVID-19 pandemic on antimicrobial resistance among paediatrics and the possible strategies to minimize the menace of antimicrobial resistance. Recent Findings: Recent findings indicate that the COVID-19 pandemic has direct as well as indirect impact on the development of antimicrobial resistance among paediatric population. Summary: This review article shows the impact of COVID-19 on the development of antimicrobial resistance and strategies to prevent it with special reference to antimicrobial stewardship programmes among paediatric population.

Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility.

Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.

Safety, efficacy, and immunogenicity of COVAXIN: A review

COVAXIN was granted restricted emergency approval based on safety and immunogenicity studies alone. The approval was heavily questioned leading to controversy regarding safety concerns and unethical trial allegations resulting in lack of trust and vaccine hesitancy among common people. In this article, we aimed to review the scientific evidence regarding the safety and immunogenicity of COVAXIN. Adverse events reported in phase-I/II COVAXIN trials were mild to moderate with no serious adverse events. The incidence of adverse events due to COVAXIN was comparable to other inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines like BBIBP-CorV and CoronaVac. COVAXIN has also demonstrated a similar immunogenicity profile and enhanced immune response as reported by other inactivated vaccines. COVAXIN has demonstrated an enhanced humoral and cell-mediated immune response among vaccine recipients. COVAXIN vaccinated human serum has also shown comparable antibody neutralization activity against SARS-CoV-2 variant B.1.1.7, B.1.617, and other heterologous strains. Evidence suggests that COVAXIN is a safe, well-tolerated, and immunogenic coronavirus disease 2019 vaccine. Its stated efficacy of 77.8% significantly exceeds the World Health Organization’s recommendations. However, the COVAXIN phase-III clinical trial data need to be peer reviewed for better transparency and building public confidence in indigenously developed vaccine and shedding COVAXIN hesitancy among common masses. © 2021 Mukhtar Ahmad Dar et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Rays of immunity: Role of sunshine vitamin in management of COVID-19 infection and associated comorbidities.

The catastrophic pandemic engendered due to the Novel coronavirus (COVID-19) outbreak which causes severe clinical afflictions on the respiratory system has severely high morbidity and mortality rates. The requirement of novel compounds is at utmost importance due to lack of targeted drug molecule to treat the afflictions and restrict the viral infection and for the usage of prophylactic treatment to avoid the spread of the infection is of utmost importance. Vitamin D is one such naturally available multifunctional molecule, which plays an eminent role in the immune system and instigation of numerous cellular pathways further promoting health benefits and enhancing the human quality of life. This article reviews the current standpoint scenario and future prevalence of vitamin D supplementation in the management of covid-19 patients. Novel findings of Vitamin D suggest that along with regulation of cell growth, neuroprotective and mood-stabilizing effects, it regulates the immune response also modulate cytokine Interleukin-6 (IL-6) by inducing progesterone-induced blocking factor (PIBF), given the IL-6 levels are considerably high in COVID-19 patients which increases the further complications. Vitamin D also have its effect on angiotensin converting enzyme (ACEII) inhibitor through which the COVID-19 virus makes cell entry. Numerous research data elucidate the play of Vitamin D, in complications of COVID-19 including the most common comorbid conditions, neurological manifestations and immunological aspects makes it an ideal molecule for adjuvant therapy. Including Vitamin D as add-on therapy in the management of COVID-19 might aid the arrest of infection and helps fight this arduous epidemic.

CRISPR detectives against SARS-CoV-2: a major setback against COVID-19 blowout.

The emergence of SARS-CoV-2 has brought the world to a standstill, and till date, effective treatments and diagnostics against this idiosyncratic pathogen are lacking. As compared to the standard WHO/CDC qPCR detection method, which consumes several hours for detection, CRISPR-based SHERLOCK, DETECTR, and FELUDA have emerged as rapid diagnostic tools for the detection of the RNA genome of SARS-CoV-2 within an hour with 100% accuracy, specificity, and sensitivity. These attributes of CRISPR-based detection technologies have taken themselves one step ahead of available detection systems and are emerging as an inevitable tool for quick detection of the virus. Further, the discovery of Cas13s nucleases and their orthologs has opened a new corridor for exploitation of Cas13s as an antiviral therapy against SARS-CoV-2 and other viral diseases. One such approach is Prophylactic Antiviral CRISPR in huMAN cells (PACMAN), which needs a long haul to bring into therapy. The approval of SHERLOCK as the first CRISPR-based SARS-CoV-2 test kit by the FDA, for emergency diagnosis of COVID-19 patients, has given positive hope to scientists that sooner human trials of CRISPR-based therapy will be ratified. In this review, we have extensively reviewed the present CRISPR-based approaches, challenges, and future prospects in the light of diagnostics and therapeutics against SARS-CoV-2. KEY POINTS: • The discovery of Cas12 and Cas13 siblings allowed scientists to detect the viral genes. • Cas13d's identification aided scientists in precisely cleaving the SARS-CoV-2 ssRNA. • CRISPR-Cas system acts as "molecular detector and antiviral proctor."

MCP-1: Function, regulation, and involvement in disease.

MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of inflammation, where it attracts or enhances the expression of other inflammatory factors/cells. It leads to the advancement of many disorders by this main mechanism of migration and infiltration of inflammatory cells like monocytes/macrophages and other cytokines at the site of inflammation. MCP-1 has been inculpated in the pathogenesis of numerous disease conditions either directly or indirectly like novel corona virus, cancers, neuroinflammatory diseases, rheumatoid arthritis, cardiovascular diseases. The elevated MCP-1 level has been observed in COVID-19 patients and proven to be a biomarker associated with the extremity of disease along with IP-10. This review will focus on involvement and role of MCP-1 in various pathological conditions.

Computational screening of FDA approved drugs of fungal origin that may interfere with SARS-CoV-2 spike protein activation, viral RNA replication, and post-translational modification: a multiple target approach.

Coronavirus spread is an emergency reported globally, and a specific treatment strategy for this significant health issue is not yet identified. COVID-19 is a highly contagious disease and needs to be controlled promptly as millions of deaths have been reported. Due to the absence of proficient restorative alternatives and preliminary clinical restrictions, FDA-approved medications can be a decent alternative to deal with the coronavirus malady (COVID-19). The present study aims to meet the imperative necessity of effective COVID-19 drug treatment with a computational multi-target drug repurposing approach. This study focused on screening the FDA-approved drugs derived from the fungal source and its derivatives against the SARS-CoV-2 targets. All the selected drugs showed good binding affinity towards these targets, and out of them, bromocriptine was found to be the best candidate after the screening on the COVID-19 targets. Further, bromocriptine is analyzed by molecular simulation and MM-PBSA study. These studies suggested that bromocriptine can be the best candidate for TMPRSS2, Main protease, and RdRp protein. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00089-8.

Peptide-like and small-molecule inhibitors against Covid-19.

Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.Communicated by Ramaswamy H. Sarma.