Chemokines and chemokine receptors during COVID-19 infection.

Chemokines are crucial inflammatory mediators needed during an immune response to clear pathogens. However, their excessive release is the main cause of hyperinflammation. In the recent COVID-19 outbreak, chemokines may be the direct cause of acute respiratory disease syndrome, a major complication leading to death in about 40% of severe cases. Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection. Here, we review the role of chemokines and their receptors in COVID-19 pathogenesis to better understand the disease immunopathology which may aid in developing possible therapeutic targets for the infection.

Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Microvascular significance of TGF-ß axis activation in COVID-19.

As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs. Notably, anticoagulation improves outcomes in some COVID-19 patients. The protein transforming growth factor-beta (TGF-ß1) has constitutive roles in maintaining a healthy microvasculature through its roles in regulating inflammation, clotting, and wound healing. However, after infection (including viral infection) TGF-ß1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-ß signaling in immune cells and its localization in areas of microvascular injury are now well-described in COVID-19, and such events may contribute to the acute respiratory distress syndrome and skin micro-thrombosis outcomes frequently seen in severe COVID-19. The high concentration of TGF-ß in platelets and in other cells within microvascular thrombi, its ability to activate the clotting cascade and dysregulate immune pathways, and its pro-fibrotic properties all contribute to a unique milieu in the COVID-19 microvasculature. This unique environment allows for propagation of microvascular clotting and immune dysregulation. In this review we summarize the physiological functions of TGF-ß and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-ß inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation.

Critically ill patients with COVID-19 show lung fungal dysbiosis with reduced microbial diversity in patients colonized with Candida spp.

BACKGROUND: The COVID-19 pandemic has intensified interest in how the infection affects the lung microbiome of critically ill patients and how it contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of critically ill patients with COVID-19 in comparison to patients without COVID-19. METHODS: We performed an internal transcribed spacer 2 (ITS2) profiling with the Illumina MiSeq platform on 26 respiratory specimens from patients with COVID-19 as well as from 26 patients with non-COVID-19 pneumonia. RESULTS: Patients with COVID-19 were more likely to be colonized with Candida spp. ARDS was associated with lung dysbiosis characterized by a shift to Candida species colonization and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in colonized patients with COVID-19. In patients with COVID-19 not colonized with Candida spp., ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and 1 Aspergillus spp.-positive specimen. In addition, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp. among patients with COVID-19. CONCLUSION: Our study underpins that ARDS in patients with COVID-19 is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.

Recent advances in passive immunotherapies for COVID-19: The Evidence-Based approaches and clinical trials.

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial and political obstacles, serious adverse effects (AEs), the impossibility of using vaccines in certain groups of people in the community, and viral evasion due to emerging novel variants of SARS-CoV-2 in many countries. For these reasons, passive immunotherapy has been considered a complementary remedy and a promising way to manage COVID-19. These approaches arebased on reduced inflammation due to inhibiting cytokine storm phenomena, immunomodulation,preventing acute respiratory distress syndrome (ARDS), viral neutralization, anddecreased viral load. This article highlights passive immunotherapy and immunomodulation approaches in managing and treating COVID-19 patients and discusses relevant clinical trials (CTs).

The risk factor for instability metabolic health and severity.

Coronavirus disease -19 (COVID-19) pandemic has extended from late 2019 and continues to this day. The degree of the disease is related to some factors, including age and comorbidities. Obesity is now more widely considered as a main factor of infection, mainly because it has been shown that individuals who are obese have a more severe course of infection with COVID-19. This review study summarized the relationship between the risk of obesity and COVID-19 and detected a difference in reporting from the period of the first pandemic in China to more recent studies. Obesity is a risk factor for developing signs and symptoms of patients with COVID-19 and this review will benefit clinicians by recognizing the role of obesity when giving COVID-19 diagnosis, follow-up, and treatment programs.

Could Statin Therapy Be Useful in Patients With Coronavirus Disease 2019 (COVID-19)?

Acute respiratory distress syndrome (ARDS), resulting from an exaggerated inflammatory response, is the main cause of death from the coronavirus disease 2019 (COVID-19). Apart from respiratory infection, COVID-19 patients can develop cardiovascular disorders such as myocardial injury and myocarditis, pericarditis, cardiac arrest and arrhythmias, cardiomyopathy, heart failure, coagulation abnormalities and thrombosis. Statins can beneficially affect inflammation, oxidative stress, coagulation, thrombosis, angiotensin converting enzyme receptor, lipid rafts, and endothelial function. In this narrative review, we provide a critical overview of the current evidence and future perspectives on the use of statins to modulate the severity, duration and complications of COVID-19 through their pleiotropic properties.

Bioprospecting of microalgae metabolites against cytokine storm syndrome during COVID-19.

In viral respiratory infections, disrupted pathophysiological outcomes have been attributed to hyper-activated and unresolved inflammation responses of the immune system. Integration between available drugs and natural therapeutics have reported benefits in relieving inflammation-related physiological outcomes and microalgae may be a feasible source from which to draw from against future coronavirus-infections. Microalgae represent a large and diverse source of chemically functional compounds such as carotenoids and lipids that possess various bioactivities, including anti-inflammatory properties. Therefore in this paper, some implicated pathways causing inflammation in viral respiratory infections are discussed and juxtaposed along with available research done on several microalgal metabolites. Additionally, the therapeutic properties of some known anti-inflammatory, antioxidant and immunomodulating compounds sourced from microalgae are reported for added clarity.

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.

Case Report: Prolonged VV-ECMO (111 Days) Support in a Patient With Severe COVID-19.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be a lifesaving rescue therapy for patients with severe coronavirus disease 2019 (COVID-19). However, little is known regarding the efficacy of prolonged ECMO (duration longer than 14 days) in patients with COVID-19. In this case report, we report the successful use of prolonged VV-ECMO (111 days) in a 61-year-old man with severe COVID-19. Given the high mortality rate of severe COVID-19, this case provided evidence for use of prolonged VV-ECMO as supportive care in patients with severe COVID-19.

Concept design of the physical structure for ICU ventilators for COVID-19 pandemic.

A new disease known as COVID-19 caused by the SARS CoV2 virus has engulfed the entire world and led to a global pandemic situation. Till December 9, 2020, the disease has infected 68 million people worldwide and more than 1.56 million people have been killed. The origin of the COVID-19 disease has been traced back to the bats, but the intermediary contact is unknown. The disease spreads by respiratory droplets and contaminated surfaces. In most cases, the virus shows mild symptoms such as fever, fatigue, dyspnea, cough, etc. which may become severe if appropriate precautions are not adhered to. For people with comorbidities (usually elderly) the disease may turn deadly and cause pneumonia, Acute Respiratory Distress Syndrome (ARDS), and multi-organ failure, thereby affecting a person's ability to perform normal breathing which may put them on ventilator support. The virus causes Acute Respiratory Distress Syndrome (ARDS) that can lead to multi-organ failure in the most severe form. A patient suffering from ARDS must be put on a mechanical ventilator. These assistive devices help patients with respiratory disorders perform normal breathing. Presently nearly sixty thousand COVID-19 patients are in critical condition worldwide, fighting for survival requiring ventilator support. In India, the number stands close to eight thousand such individuals especially when the second wave of COVID-19 is expected to spread globally with initial signs arising from European and Middle East countries. With a large number of patients requiring ventilators, it puts a huge strain on the already weak health infrastructure of the developing countries. This is where some manufacturing and automobile companies have stepped in to help hospitals by developing ventilators at a faster rate and lower costs without comprising on the quality with the support of different government initiatives. This paper aims to study the basic requirements to be considered while designing the physical structure of an elementary level ICU ventilator for the hospital environment. The challenges related to research in electronic wiring of a mechanical ventilator, the overall structural design, and surrounding base could be appropriately done for different loads by simulating the conditions on tools like ANSYS software with accurate dimensions which could improve their future designs.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via Angiotensin-Converting Enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the Acute Respiratory Distress Syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people, with sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

Lung Ultrasound May Support Diagnosis and Monitoring of COVID-19 Pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is characterized by severe pneumonia and/or acute respiratory distress syndrome in about 20% of infected patients. Computed tomography (CT) is the routine imaging technique for diagnosis and monitoring of COVID-19 pneumonia. Chest CT has high sensitivity for diagnosis of COVID-19, but is not universally available, requires an infected or unstable patient to be moved to the radiology unit with potential exposure of several people, necessitates proper sanification of the CT room after use and is underutilized in children and pregnant women because of concerns over radiation exposure. The increasing frequency of confirmed COVID-19 cases is striking, and new sensitive diagnostic tools are needed to guide clinical practice. Lung ultrasound (LUS) is an emerging non-invasive bedside technique that is used to diagnose interstitial lung syndrome through evaluation and quantitation of the number of B-lines, pleural irregularities and nodules or consolidations. In patients with COVID-19 pneumonia, LUS reveals a typical pattern of diffuse interstitial lung syndrome, characterized by multiple or confluent bilateral B-lines with spared areas, thickening of the pleural line with pleural line irregularity and peripheral consolidations. LUS has been found to be a promising tool for the diagnosis of COVID-19 pneumonia, and LUS findings correlate fairly with those of chest CT scan. Compared with CT, LUS has several other advantages, such as lack of exposure to radiation, bedside repeatability during follow-up, low cost and easier application in low-resource settings. Consequently, LUS may decrease utilization of conventional diagnostic imaging resources (CT scan and chest X-ray). LUS may help in early diagnosis, therapeutic decisions and follow-up monitoring of COVID-19 pneumonia, particularly in the critical care setting and in pregnant women, children and patients in areas with high rates of community transmission.