Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

The effect of Vitamin C and Zn supplementation on the immune system and clinical outcomes in COVID-19 patients.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases.

The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.

The impact of lymphoid memory cells in different ages of COVID-19 patients.

Coronaviruses are highly pathogenic and transmissible viruses. The SARS-CoV-2 virus that emerged in December 2019 is increasingly recognized as a serious, worldwide public health concern. Respiratory infections and the hyper-inflammatory response induced by SARS-CoV-2 play a key role in disease severity and death in infected COVID-19 patients. However, much uncertainty still exists about the pathogenesis and various effects of COVID-19 on immune system. It seems that memory T cells can reduce the severity of COVID-19 infection by inducing a protective immune response. Memory T cells along with protective antibodies are the main defenses and also protective barrier against recurrent COVID-19 infection. The role of Memory T cells varies in different ages and the severity of COVID-19 infection varies between children, adults and the elderly. Furthermore, the aim of this review is to evaluate the role of memory cells in mild, moderate and severe infected COVID-19 patients with different ages.

Successful treatment of prolonged COVID-19 with Bamlanivimab in a patient with severe B-Cell aplasia due to treatment with an anti-CD20 monoclonal antibody: A case report.

A 71-year-old female patient with B-cell depletion due to treatment with an anti-CD20 monoclonal antibody was admitted for worsening COVID-19. Overall, she had persistent viral shedding, worsening respiratory failure, and progressive pneumonia that did not improve despite dexamethasone and antibiotic therapy. After administration of bamlanivimab, a monoclonal antibody with high affinity for the receptor-binding domain of the SARS-CoV-2 spike protein, inflammatory markers rapidly decreased, SARS-CoV2 RT-PCR became negative, and the patient improved clinically and radiologically. In conclusion, we demonstrated successful treatment of prolonged COVID-19 in a patient with severe B-cell aplasia with a virus-neutralizing monoclonal antibody.

Metabolomics reveals sex-specific metabolic shifts and predicts the duration from positive to negative in non-severe COVID-19 patients during recovery process.

Metabolic profiling in COVID-19 patients has been associated with disease severity, but there is no report on sex-specific metabolic changes in discharged survivors. Herein we used an integrated approach of LC-MS-and GC-MS-based untargeted metabolomics to analyze plasma metabolic characteristics in men and women with non-severe COVID-19 at both acute period and 30 days after discharge. The results demonstrate that metabolic alterations in plasma of COVID-19 patients during the recovery and rehabilitation process were presented in a sex specific manner. Overall, the levels of most metabolites were increased in COVID-19 patients after the cure relative to acute period. The major plasma metabolic changes were identified including fatty acids in men and glycerophosphocholines and carbohydrates in women. In addition, we found that women had shorter length of hospitalization than men and metabolic characteristics may contribute to predict the duration from positive to negative in non-severe COVID-19 patients. Collectively, this study shed light on sex-specific metabolic shifts in non-severe COVID-19 patients during the recovery process, suggesting a sex bias in prognostic and therapeutic evaluations based on metabolic profiling.

Recovery scenario and immunity in COVID-19 disease: A new strategy to predict the potential of reinfection.

Background: The recent ongoing outbreak of coronavirus disease 2019 (COVID-19), still is an unsolved problem with a growing rate of infected cases and mortality worldwide. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is targeting the angiotensin-converting enzyme 2 (ACE2) receptor and mostly causes a respiratory illness. Although acquired and resistance immunity is one of the most important aspects of alleviating the trend of the current pandemic; however, there is still a big gap of knowledge regarding the infection process, immunopathogenesis, recovery, and reinfection. Aim of Review: To answer the questions regarding "the potential and probability of reinfection in COVID-19 infected cases" or "the efficiency and duration of SARS-CoV-2 infection-induced immunity against reinfection" we critically evaluated the current reports on SARS-CoV-2 immunity and reinfection with special emphasis on comparative studies using animal models that generalize their finding about protection and reinfection. Also, the contribution of humoral immunity in the process of COVID-19 recovery and the role of ACE2 in virus infectivity and pathogenesis has been discussed. Furthermore, innate and cellular immunity and inflammatory responses in the disease and recovery conditions are reviewed and an overall outline of immunologic aspects of COVID-19 progression and recovery in three different stages are presented. Finally, we categorized the infected cases into four different groups based on the acquired immunity and the potential for reinfection. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to predict the potential of reinfection in each identified category. This classification may help to distribute resources more meticulously to determine: who needs to be serologically tested for SARS-CoV-2 neutralizing antibodies, what percentage of the population is immune to the virus, and who needs to be vaccinated.

Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions.

INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.