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Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has led to the ongoing global pandemic. Although most patients experience no or only mild symptoms, some patients can develop severe illness, such as progressive pneumonia, acute respiratory distress syndrome, secondary hemophagocytic lymphohistiocytosis and multiple organ failure caused by cytokine release syndrome. A majority of COVID-19 patients also develop gastrointestinal symptoms. These can present special challenges to the management of patients with inflammatory bowel disease (IBD) due to potential interactions between the immune response related to SARS-CoV-2 infection and dysregulated immunity associated with IBD. In this context, the pathogenesis of COVID-19 is reviewed in order to address these questions regarding immune interactions between COVID-19 and IBD.

The healthy immune system eliminates pathogens and maintains tissue homeostasis through extraordinarily complex networks with feedback systems while avoiding potentially massive tissue destruction. Many parameters influence humoral and cellular vaccine responses, including intrinsic and extrinsic, environmental, and behavioral, nutritional, perinatal and administrative parameters. The relative contributions of persisting antibodies and immune memory as well as the determinants of immune memory induction, to protect against specific diseases are the main parameters of long-term vaccine efficacy. Natural and vaccine-induced immunity and monoclonal antibody immunotherapeutic, may be evaded by SARS-CoV-2 variants. Besides the complications of the production of COVID-19 vaccinations, there is no effective single treatment against COVID-19. However, administration of a combined treatment at different stages of COVID-19 infection may offer some cure assistance. Combination treatment of antiviral drugs and immunomodulatory drugs may reduce inflammation in critical COVID-19 patients with cytokine release syndrome. Molnupiravir, remdesivir and paxlovid are the approved antiviral agents that may reduce the recovery time. In addition, immunomodulatory drugs such as lactoferrin and monoclonal antibodies are used to control inflammatory responses in their respective auto-immune conditions. Therefore, the widespread occurrence of highly transmissible variants like Delta and Omicron indicates that there is still a lot of work to be done in designing efficient vaccines and medicines for COVID-19. In this review, we briefly discussed the immunological response against SARS-CoV-2 and the vaccines approved by the World Health Organization (WHO) for COVID-19, their mechanisms, and side effects. Moreover, we mentioned various treatment trials and strategies for COVID-19. [Display omitted] • Available vaccines and treatments in COVID-19 management of, including their effect against SARS-CoV-2 variants of concern. • Some vaccines against SARS-CoV-2 are under emergency approval, and the mRNA vaccine shows the most effective technique. • Paxlovid, molnupiravir, and remdesivir are the currently effective antiviral agents against Omicron subvariants of SARS-CoV-2. • Bebtelovimab is the only monoclonal antibody that is active against all Omicron subvariants. • Some supportive treatments against SARS-CoV-2 such as lactoferrin show immunomodulatory and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a member of the Coronaviridae family. On March 11, 2020 the World Health Organization (WHO) has named the newly emerged rapidly-spreading epidemic as a pandemic. Besides the risk-reduction measures such as physical and social distancing and vaccination, a wide range of treatment modalities have been developed; aiming to fight the disease. The immune system is known as a double-edged sword in COVID-19 pathogenesis, with respect to its role in eliminating the pathogen and in inducing complications such as cytokine storm syndrome. Hence, immune-based therapeutic approaches have become an interesting field of COVID-19 research, including corticosteroids, intravenous immunoglobulins (IVIG), interferon therapy, and more COVID-19-specific approaches such as anti-SARS-CoV-2-monoclonal antibodies. Herein, we did a comprehensive review on immune-based therapeutic approaches for COVID-19. Not applicable. [Display omitted] • Since the emergence of the virus, COVID-19 has caused morbidities and mortalities worldwide. • The immune system plays a dual role, eliminating pathogens and inducing poorly regulated responses. • Immune-based therapeutic approaches affect both roles and help to resolve disease complications. • These approaches are a promising candidate in controlling poorly regulated responses especially in severely ill patients. • Examples of such modalities include corticosteroids, IVIG, interferons, and monoclonal antibodies. [ABSTRACT FROM AUTHOR]

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19. • BromAc is a strong mucolytic for COVID-19 sputum ex vivo. • Select chemokines and cytokines were downregulated following BromAc exposure. • Mucolytic and anti-inflammatory effects of BromAc were dose-dependent. • Further assessment of BromAc in COVID-19 clinical trials is warranted. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is a multi-tasking cytokine that represents high activity in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cancer. High concentration of this pleiotropic cytokine accounts for hyperinflammation and cytokine storm, and is related to multi-organ failure in patients with SARS-CoV-2 induced disease. IL-6 promotes lymphopenia and increases C-reactive protein (CRP) in such cases. However, blockade of IL-6 is not a full-proof of complete response. Hypoxia, hypoxemia, aberrant angiogenesis and chronic inflammation are inter-related events occurring as a response to the SARS-CoV-2 stimulatory effect on high IL-6 activity. Taking both pro- and anti-inflammatory activities will make complex targeting IL-6 in patient with SARS-CoV-2 induced disease. The aim of this review was to discuss about interactions occurring within the body of patients with SARS-CoV-2 induced disease who are representing high IL-6 levels, and to determine whether IL-6 inhibition therapy is effective for such patients or not. We also address the interactions and targeted therapies in cancer patients who also have SARS-CoV-2 induced disease. • IL-6 is a hallmark of inflammatory feature in severe/critical SARS-CoV-2 induced disease. • CRP level is a predictor of response to IL-6 inhibitor therapy. • The efficacy of tocilizumab is moderate in severe SARS-CoV-2 induced disease. • SARS-CoV-2-induced IL-6 seemingly strengthens cancer aggression. • IL-6 inhibitors can go with ICI in cancer (not in SARS-CoV-2 induced disease). [ABSTRACT FROM AUTHOR]

Hyperinflammatory response caused by infections such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases organ failure, intensive care unit admission, and mortality. Cytokine storm in patients with Coronavirus Disease 2019 (COVID-19) drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor complex nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and its downstream target gene interleukin 6 (IL6) which interacts with IL6 receptor (IL6R) and the IL6 signal transduction protein (IL6ST or gp130) to regulate intracellular inflammatory pathways. In this study, we compare transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knockdown) cell lines in order to identify a mechanism by which antidepressants such as fluoxetine demonstrate non-serotonergic, anti-inflammatory effects. Our results demonstrate a critical role for IL6ST and NF-kappaB Subunit 1 (NFKB1) in fluoxetine's ability to act as a potential therapy for hyperinflammatory states such as asthma, sepsis, and COVID-19. [Display omitted] • Fluoxetine treatment elicits genetic changes which parallel those caused by IL6ST or NFKB1 knockdown. • Fluoxetine's anti-inflammatory mechanism of action may depend upon NF-kappaB/IL6ST signaling. • The anti-inflammatory effects of fluoxetine are likely independent of its monoaminergic mechanism. • The anti-inflammatory effects of fluoxetine may prevent cytokine storm associated with COVID-19. [ABSTRACT FROM AUTHOR]

• GI symptoms are common in patients with COVID-19, which may be related to abundant ACE2 expression in the intestinal epithelium. • Changes in ACE2 expression may affect functions of B0AT1 in AA absorption, thus contributing to the GI symptoms in COVID-19 patients. • Immune irregularities associated with IBD share cellular components with immune responses in COVID-19. • Immune modulating treatment for IBD may have overlapping effect on outcome of COVID-19 in IBD patients. Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has led to the ongoing global pandemic. Although most patients experience no or only mild symptoms, some patients can develop severe illness, such as progressive pneumonia, acute respiratory distress syndrome, secondary hemophagocytic lymphohistiocytosis and multiple organ failure caused by cytokine release syndrome. A majority of COVID-19 patients also develop gastrointestinal symptoms. These can present special challenges to the management of patients with inflammatory bowel disease (IBD) due to potential interactions between the immune response related to SARS-CoV-2 infection and dysregulated immunity associated with IBD. In this context, the pathogenesis of COVID-19 is reviewed in order to address these questions regarding immune interactions between COVID-19 and IBD. [ABSTRACT FROM AUTHOR]

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed. [ABSTRACT FROM AUTHOR]

• Effect of sex hormones on COVID-19 outcome bias in males and females. • Effect of immunological factors on COVID-19 outcome bias in males and females. • Angiotensin-converting enzyme-2 (ACE2) system and COVID-19 outcome in males and females. • Correlation between smoking and COVID-19 incidence in males and females. • Possible therapeutic options for COVID-19. The severe form of COVID-19 has significant sex disparities, with high fatalities commonly reported among males than females. The incidence of COVID-19 has also been higher in males compared with their female counterparts. This trend could be attributed to a better responsive and robust immune system in females. Cytokine storm is one of the pathophysiological features of severe COVID-19, and it occurs as a result of over-activation of immune cells leading to severe inflammation and tissue damage. Nevertheless, it is well modulated in females compared to their male counterparts. Severe inflammation in males is reported to facilitate progression of mild to severe COVID-19. The sex hormones, estrogens and androgens which exist in varying functional levels respectively in females and males are cited as the underlying cause for the differential immune response to COVID-19. Evidence abounds that estrogen modulate the immune system to protect females from severe inflammation and for that matter severe COVID-19. On the contrary, androgen has been implicated in over-activation of immune cells, cytokine storm and the attendant severe inflammation, which perhaps predispose males to severe COVID-19. In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19. [ABSTRACT FROM AUTHOR]

• Candesartan downregulates expression of many glutamate upregulated genes in cultured neurons. • Glutamate upregulated genes in neurons positively correlate with COVID-19 upregulated genes. • Candesartan gene downregulation negatively correlates with COVID-19 upregulated genes. • Candesartan downregulates genes involved in the COVID-19 cytokine storm. Angiotensin receptor blockers (ARBs) reducing inflammation and protecting lung and brain function, could be of therapeutic efficacy in COVID-19 patients. Using GSEA, we compared our previous transcriptome analysis of neurons injured by glutamate and treated with the ARB Candesartan (GSE67036) with transcriptional signatures from SARS-CoV-2 infected primary human bronchial epithelial cells (NHBE) and lung postmortem (GSE147507), PBMC and BALF samples (CRA002390) from COVID-19 patients. Hundreds of genes upregulated in SARS-CoV-2/COVID-19 transcriptomes were similarly upregulated by glutamate and normalized by Candesartan. Gene Ontology analysis revealed expression profiles with greatest significance and enrichment, including proinflammatory cytokine and chemokine activity, the NF-kappa B complex, alterations in innate and adaptive immunity, with many genes participating in the COVID-19 cytokine storm. There are similar injury mechanisms in SARS-CoV-2 infection and neuronal injury, equally reduced by ARB treatment. This supports the hypothesis of a therapeutic role for ARBs, ameliorating the COVID-19 cytokine storm. [ABSTRACT FROM AUTHOR]

• Propolis, made by bees from bioactive plant resins, has antiviral activity. • Propolis potentially can interfere with host cell invasion by SARS-CoV-2. • Propolis blocks proinflammatory PAK1, a kinase highly expressed in COVID19 patients. • Standardized propolis has consistent properties for lab and clinical research. • Propolis is a safe widely consumed functional food with medicinal properties. Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. This mechanism involves PAK1 overexpression, which is a kinase that mediates coronavirus-induced lung inflammation, fibrosis, and immune system suppression. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-α. This immunoregulation involves monocytes and macrophages, as well as Jak2/STAT3, NF-kB, and inflammasome pathways, reducing the risk of cytokine storm syndrome, a major mortality factor in advanced COVID-19 disease. Propolis has also shown promise as an aid in the treatment of various of the comorbidities that are particularly dangerous in COVID-19 patients, including respiratory diseases, hypertension, diabetes, and cancer. Standardized propolis products with consistent bioactive properties are now available. Given the current emergency caused by the COVID-19 pandemic and limited therapeutic options, propolis is presented as a promising and relevant therapeutic option that is safe, easy to administrate orally and is readily available as a natural supplement and functional food. [ABSTRACT FROM AUTHOR]