Causes Coronavirus Disease 2019 Research Articles

Luteolin inhibits spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binding to angiotensin-converting enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that poses a serious threat to global public health. In an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike (S) protein to engage with angiotensin-converting enzyme 2 (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, with luteolin being a flavonoid that can significantly inhibit SARS-CoV infection. However, whether it can block the interaction between the S-protein RBD of SARS-CoV-2 and ACE2 has not yet been elucidated. Here, we investigated the effects of luteolin on the binding of the S-protein RBD to ACE2. By employing a competitive binding assay in vitro, we found that luteolin significantly blocked the binding of S-protein RBD to ACE2 with IC50 values of 0.61 mM, which was confirmed by the neutralized infection with SARS-CoV-2 pseudovirus in vivo. A surface plasmon resonance-based competition assay revealed that luteolin significantly affects the binding of the S-protein RBD to the ACE2 receptor. Molecular docking was performed to predict the binding sites of luteolin to the S-protein RBD-ACE2 complex. The active binding sites were defined based on published literature, and we found that luteolin might interfere with the mixture at residues including LYS353, ASP30, and TYR83 in the cellular ACE2 receptor and GLY496, GLN498, TYR505, LEU455, GLN493, and GLU484 in the S-protein RBD. These residues may together form attractive charges and destroy the stable interaction of S-protein RBD-ACE2. Luteolin also inhibits SARS-CoV-2 spike protein-induced platelet spreading, thereby inhibiting the binding of the spike protein to ACE2. Our results are the first to provide evidence that luteolin is an anti-SARS-CoV-2 agent associated with interference between viral S-protein RBD-ACE2 interactions.

Repurposing of RAS-Pathway Mediated Drugs for Intestinal Inflammation Related Diseases for Treating SARS-CoV-2 Infection

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is an emerging zoonotic virus, which causes Coronavirus Disease 2019 (COVID-19). Entry of coronaviruses into the cell depends on binding of the viral spike (S) proteins to cellular receptors Angiotensin-converting enzyme 2 (ACE2). The virus-mediated reduction of ACE2/Ang1-7 causes flooding of inflammatory cytokines. A similar scenario of hyper immunologic reaction has been witnessed in the context of Intestinal Inflammatory Diseases (IIDs) with the deregulation of ACE2. This review summarizes several IIDs that lead to such susceptible conditions. It discusses suitable mechanisms of how ACE2, being a crucial regulator of the Renin-Angiotensin System (RAS) signaling pathway, can affect the physiology of intestine as well as lungs, the primary site of SARS-CoV-2 infection. ACE2, as a SARS-CoV-2 receptor, establishes a critical link between COVID-19 and IIDs. Intercessional studies targeting the RAS signaling pathway in patients may provide a novel strategy for addressing the COVID-19 crisis. Hence, the modulation of these key RAS pathway members can be beneficial in both instances. However, it's difficult to say how beneficial are the ACE inhibitors (ACEI)/ Angiotensin II type-1 receptor blockers (ARBs) during COVID-19. As a result, much more research is needed to better understand the relationship between the RAS and SARS-CoV-2 infection.

Crystallographic and biophysical analysis of the fusion core from SARS‐CoV‐2 spike protein

AbstractSevere acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) is a newly emerging infectious pathogen causing coronavirus disease 2019 (COVID‐19). The virus primarily infects cells via its spike glycoprotein, which is cleaved into S1 and S2 subunits to aid in cell attachment and membrane fusion, respectively. Heptad repeat 1 (HR1) and heptad repeat 2 (HR2) of the S2 subunit are essential for membrane fusion, culminating in an expected six‐helix bundle termed fusion core. To better understand the structural and biophysical features of the SARS‐CoV‐2 fusion core, we designed, constructed, and bacterially produced a recombinant single‐chain HR1‐L6‐HR2 protein and conducted a series of biochemical and biophysical experiments. Our findings demonstrate that the HR1‐L6‐HR2 protein spontaneously assembles into a highly stable trimeric complex, further confirmed by x‐ray crystallographic analysis. The crystal structure of the fusion core reveals a trimeric coiled‐coil structure of HR1 antiparallelly surrounded by three HR2 to form a six‐helical bundle. Additionally, four residues of HR1 that contribute to binding with HR2 through the formation of hydrogen bonds and salt bridges were observed. These results indicate that the SARS‐CoV‐2 fusion core exhibits similar characteristics to other class I viral glycoproteins, suggesting potential for drug repurposing as an alternative strategy to combat COVID‐19.

SARS-CoV-2 Neutralization Assay System using Pseudo-lentivirus

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects humans' lower respiratory tracts and causes coronavirus disease-2019 (COVID-19). Neutralizing antibodies is one of the adaptive immune system responses that can reduce SARS-CoV-2 infection. This study aimed to develop a SARS-CoV-2 neutralization assay system using pseudo-lentivirus.METHODS: The plasmid used for pseudo-lentivirus production was characterized using restriction analysis. The gene encoding for SARS-CoV-2 spike protein was confirmed using sequencing. The transfection pseudo-lentivirus optimal condition was determined by choosing the transfection reagents and adding centrifugation step. Optimal pseudo-lentivirus infection was analysed using fluorescent assay and luciferase assay. The optimal condition of pseudo-lentivirus infection was determined by the target cell type and the number of pseudo-lentiviruses used for neutralization test. SARS-CoV-2 pseudo-lentivirus was used to detect neutralizing antibodies from serum samples.RESULTS: The plasmid used for pseudo-lentivirus production was characterized and confirmed to have no mutations. Lipofectamine 2000 reagent generated pseudo-lentivirus with a higher ability to infect target cells, as indicated by a percentage green fluorescent protein (GFP) of 12.68%. Pseudo-lentivirus centrifuged obtained more stable results in luciferase expression. Optimal pseudo-lentivirus infection conditions were obtained using puromycin-selected HEK 293T-ACE2 cells as target cells. The number of pseudo-lentiviruses used in the neutralization assay system was multiplicity of infection (MOI) 0.075. Serum A samples with a 1:10 dilution had the highest neutralizing antibody activity.CONCLUSION: This study shows that SARS-CoV-2 neutralization assay system using pseudo-lentivirus successfully detected neutralizing antibodies in human serum, which were indicated by a decrease in the percentage of pseudo-lentivirus infections.KEYWORDS: COVID-19, neutralizing antibody, neutralization assay, pseudo-lentivirus, SARS-COV-2

Vitamin D in COVID-19

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) with clinical outcome ranging from asymptomatic to severe disease, and even death to some. It posed a terrifying challenge to healthcare system worldwide. Several observational and clinical trials has reported that, Vitamin D deficiency has contributed to acute respiratory distress syndrome. Case fatality rate increases with age and comorbidities, both of which are associated with decreased Vitamin D level. Therefore, this study is done to study the prevalence of 25(OH)Vitamin D in RT-PCR positive COVID-19 cases and RT-PCR negative controls.This is a hospital based cross-sectional study conducted at Jawaharlal Nehru Institute of Medical Sciences, Manipur on 88 RT-PCR positive Covid-19 cases and 88 COVID-19 negative controls over a period of 2 years. Analysis of the sample was done by Liaison 25(OH) Vitamin D Total Chemiluminescence assay(CLIA).In this study, statistically significant (p-0.018) lower plasma 25(OH)Vitamin D level is seen in COVID-19 positive cases (median 28±20.47) when compared to Covid-19 negative controls(median 33.50±10.66). The number of 25(OH) Vitamin D deficient is higher in Covid-19 positive cases when compared to Covid-19 negative controls -46(52.3%) and 30(34%) respectively with a high statistically significant value (p-0.015).COVID-19 positive cases have higher tendency to have suboptimal plasma 25(OH) Vitamin D level which may contribute to the high hospitalization risk in COVID-19 infection. This finding is important as it can identify population at risk, and contribute to interventions in reducing the risk of hospitalization associated with COVID-19 infection.

The comparison of clinical, laboratory, and radiological findings in immunocompromised and immunocompetent patients with COVID-19: A case-control study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) with significant morbidity and mortality. We reported and compared the clinical and para-clinical findings of immunocompromised and immunocompetent COVID-19 patients in a case-control study at the Imam Khomeini hospital in Tehran, Iran. In this study, 107 immunocompromised COVID-19 patients were recruited as the case group, and 107 immunocompetent COVID-19 patients as the control group. The participants were matched based on age and sex. The patients' information was retrieved from the hospital records in an information sheet. Associations between clinical and para-clinical findings with the immune status were assessed using bivariate and multivariate analyses. The initial pulse rate and recovery time were significantly higher in immunocompromised patients (p < .05). Myalgia, nausea/vomiting, loss of appetite, headache, and dizziness were more frequently reported by the control group (p < .05). Regarding the prescribed medications' duration, Sofosbovir was used longer in the case group, while Ribavirin was used longer in the control groups (p < .05). The most common complication in the case group was acute respiratory distress syndrome, although no major complications were observed in the control group. According to the multivariate analysis, recovery time and Lopinavir/Ritonavir (Kaletra) prescription were significantly higher in the immunocompromised compared to the immunocompetent group. Recovery time was significantly longer in the immunocompromised compared to the immunocompetent group, which emphasizes the necessity of prolonged care in these high-risk patients. Also, it is recommended to investigate the effect of novel therapeutic interventions to reduce the recovery time in addition to improving the prognosis of immunodeficient patients with COVID-19.

Neurological damages in COVID-19 patients: Mechanisms and preventive interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g., cardiac and cerebral ischemia), and even death through multi-organ failure. At the early stage, the virus infects the lung epithelial cells and is slowly transmitted to the other organs including the gastrointestinal tract, blood vessels, kidneys, heart, and brain. The neurological effect of the virus is mainly due to hypoxia-driven reactive oxygen species (ROS) and generated cytokine storm. Internalization of SARS-CoV-2 triggers ROS production and modulation of the immunological cascade which ultimately initiates the hypercoagulable state and vascular thrombosis. Suppression of immunological machinery and inhibition of ROS play an important role in neurological disturbances. So, COVID-19 associated damage to the central nervous system, patients need special care to prevent multi-organ failure at later stages of disease progression. Here in this review, we are selectively discussing these issues and possible antioxidant-based prevention therapies for COVID-19-associated neurological damage that leads to multi-organ failure.

Enhancement of SARS-CoV-2 infection and growth by an ACE2-specific monoclonal antibody.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) pandemic and continues to pose a threat to global public health through genetic mutation. In this study, we have found that an angiotensin-converting enzyme 2-specific monoclonal antibody at low concentration was able to enhance SARS-CoV-2 infection and growth in cell culture. Strikingly, it promotes SARS-CoV-2 plaque formation, resulting in accurate titration of different SARS-CoV-2 variants, particularly the newly emerged Omicron variants, which otherwise cannot be determined by standard plaque assays. Quantification of infectious titers of the newly emerged variants will facilitate the development and evaluation of vaccines and antiviral drugs against SARS-CoV-2.

Providing pharmacy services during the coronavirus pandemic in Saudi Arabia (Review)

On March 2, 2020, the Kingdom of Saudi Arabia confirmed its first case of the emerging coronavirus strain that causes coronavirus disease 2019 (COVID-19). Shortly thereafter, the number of confirmed cases nationwide began to rise. Since the looming outbreak, all healthcare professionals, including pharmacists, began to work at maximum capacity and effort. The Saudi Society of Clinical Pharmacy (SSCP) recognizes the significant impact pharmacists can have during outbreaks. Based on the scientific evidence available during this outbreak, the SSCP set up an expert working group to conceptualize and draft proposed recommendations that highlight the roles and responsibilities of pharmacists during epidemics and pandemics. The SSCP working group made 28 recommendations. In addition to national and institutional guidelines, these recommendations could serve as guidance for affected entities.

Autoimmune liver diseases and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.

Evaluation of Remdesivir Utilization Pattern in Critically Ill Patients With COVID-19 in Jazan Province.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread around the world, spurring the biomedical community to find and create antiviral therapies. The agent remdesivir, which has undergone a protracted and tortuous developmental path, is one potential therapeutic strategy now being assessed in several clinical trials. A broad-spectrum antiviral drug called remdesivir has already shown antiviral effects against filoviruses. Remdesivir was suggested as an exploratory medicine early in the pandemic because in vitro tests showed it to have antiviral effectiveness against SARS-CoV-2. Methods We conducted a retrospective cohort study that examined patient data captured through an electronic medical system at the Abu Arish General Hospital between 2021 and 2022. Data analysis was performed with SPSS version 25.0 (Armonk, NY: IBM Corp.). Results A total of 88 patients were included in this study. With the usage of remdesivir, our risk model is able to forecast adverse events and the case fatality rate. In contrast to D-dimer and c-reactive proteins, we showed that alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine, and hemoglobin are relevant variables. Conclusion Our risk model can predict the adverse reactions and case fatality rate with the use of remdesivir. We demonstrated ALT, AST, serum creatinine, and hemoglobin as important variables rather than D-dimer and c-reactive proteins.

Intraduodenal Delivery of Exosome-Loaded SARS-CoV-2 RBD mRNA Induces a Neutralizing Antibody Response in Mice.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has presented numerous challenges to global health. Vaccines, including lipid-based nanoparticle mRNA, inactivated virus, and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and have been immensely helpful in controlling the pandemic. Here, we present and assess an oral mRNA vaccine based on bovine-milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor-binding domain (RBD) as an immunogen. The results indicate that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptides in 293 cells in vitro and stimulates neutralizing antibodies against RBD in mice. These results indicate that SARS-CoV-2 RBD mRNA vaccine loading with bovine-milk-derived exosomes is an easy, cheap, and novel way to introduce immunity against SARS-CoV-2 in vivo. Additionally, it also can work as a new oral delivery system for mRNA.

Patient-facing job role is associated with SARS-CoV-2 positivity among healthcare workers in long term care facilities in Minnesota, August-December, 2020.

Healthcare workers (HCWs) in long-term care facilities (LTCFs) are disproportionately affected by severe acute respiratory coronavirus virus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). To characterize factors associated with SARS-CoV-2 positivity among LTCF HCWs, we performed a retrospective cohort study among HCWs in 32 LTCFs in the Minneapolis-St Paul region. We analyzed the outcome of SARS-CoV-2 polymerase chain reaction (PCR) positivity among LTCF HCWs during weeks 34-52 of 2020. LTCF and HCW-level characteristics, including facility size, facility risk score for resident-HCW contact, and resident-facing job role, were modeled in univariable and multivariable generalized linear regressions to determine their association with SARS-CoV-2 positivity. Between weeks 34 and 52, 440 (20.7%) of 2,130 unique HCWs tested positive for SARS-CoV-2 at least once. In the univariable model, non-resident-facing HCWs had lower odds of infection (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.36-0.70). In the multivariable model, the odds remained lower for non-resident-facing HCW (OR, 0.50; 95% CI, 0.36-0.71), and those in medium- versus low-risk facilities experienced higher odds of testing positive for SARS-CoV-2 (OR, 1.47; 95% CI, 1.08-2.02). Our findings suggest that COVID-19 cases are related to contact between HCW and residents in LTCFs. This association should be considered when formulating infection prevention and control policies to mitigate the spread of SARS-CoV-2 in LTCFs.

Prolonged SARS-CoV-2 Infection and Organizing Pneumonia in a Patient with Follicular Lymphoma, Treated with Obinutuzumab—Challenging Recognition and Treatment

A Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) led to a pandemic outbreak in 2019. COVID-19's course and its treatment in immunocompromised patients are uncertain. Furthermore, there is a possibility of protracted SARS-CoV-2 infection and the need for repeated antiviral treatment. Monoclonal antibodies against CD20, which are used, among other things, in the therapy of chronic lymphocytic leukaemia and follicular lymphoma, can induct immunosuppression. We present a case report of a patient with follicular lymphoma, treated with obinutuzumab, who was diagnosed with prolonged, ongoing SARS-CoV-2 infection and related organizing pneumonia. The recognition and the treatment were challenging which makes this case noteworthy. Antiviral therapy with several medications was administrated to our patient and their temporary, positive effect was observed. Moreover, high-dose intravenous immunoglobulin was applied, because slowly decreasing IgM and IgG levels were observed. The patient also received standard treatment of organizing pneumonia. We believe that such a complex approach can create an opportunity for recovery. Physicians should be conscious of the course and treatment possibilities facing similar cases.

Community exposures among Colorado adults who tested positive for SARS-CoV-2 -A case-control study, March-December 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), is spread primarily through exposure to respiratory droplets from close contact with an infected person. To inform prevention measures, we conducted a case-control study among Colorado adults to assess the risk of SARS-CoV-2 infection from community exposures. Cases were symptomatic Colorado adults (aged ≥18 years) with a positive SARS-CoV-2 test by reverse transcription-polymerase chain reaction (RT-PCR) reported to Colorado's COVID-19 surveillance system. From March 16 to December 23, 2021, cases were randomly selected from surveillance data ≤12 days after their specimen collection date. Cases were matched on age, zip code (urban areas) or region (rural/frontier areas), and specimen collection date with controls randomly selected among persons with a reported negative SARS-CoV-2 test result. Data on close contact and community exposures were obtained from surveillance and a survey administered online. The most common exposure locations among all cases and controls were place of employment, social events, or gatherings and the most frequently reported exposure relationship was co-worker or friend. Cases were more likely than controls to work outside the home (adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI): 1.09-1.28) in industries and occupations related to accommodation and food services, retail sales, and construction. Cases were also more likely than controls to report contact with a non-household member with confirmed or suspected COVID-19 (aOR 1.16, 95% CI: 1.06-1.27). Understanding the settings and activities associated with a higher risk of SARS-CoV-2 infection is essential for informing prevention measures aimed at reducing the transmission of SARS-CoV-2 and other respiratory diseases. These findings emphasize the risk of community exposure to infected persons and the need for workplace precautions in preventing ongoing transmission.

An investigation to find the correlation between lupus anticoagulant and coagulation abnormalities in COVID-19 patients; a narrative review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which is associated with nonspecific respiratory syndromes, varying from mild symptoms of upper airway to required mechanical ventilation hypoxemia. A unique feature of this disease is COVID-19-associated coagulopathy (CAC) that linked with disease severity and hospital mortality. These patients have a profound hypercoagulable state and in patients with severe type arterial and venous thrombotic events are frequent. Abnormal coagulation parameters such as activated partial thromboplastin time (aPTT) were observed in patients with COVID-19. Regarding the above finding it could be considered as a reason to avoid anticoagulation at the both doses of therapeutic and prophylactic. A prolonged aPTT may indicate a coagulation factor deficiency or inhibitor of coagulation, which can be specific (antibody to factor VIII) or nonspecific (lupus anticoagulant, LA). LA can affect laboratory tests of blood coagulation, but is not usually associated with bleeding; however, it can be associated with thrombotic risk as a part of the antiphospholipid syndrome. In a phospholipid concentration-dependent manner LA recognizes a type of antiphospholipid antibodies (aPLs) that prolong clotting tests. In patients with antiphospholipid syndrome (APS) LA is considered as one of the laboratory criteria representing a significant risk factor of both thrombosis and pregnancy morbidity. Similarities between some of the pathophysiological features of COVID-19 and APS has been focused in several reports particularly in the most severe form, catastrophic APS. This study aimed to evaluate the effect of LA on the incidence of thrombophilia in patients with COVID-19, as well as its impact on the inflammation and finally the mortality final rate.

Reduction in the COVID-19 pneumonia case fatality rate by silver nanoparticles: A randomized case study

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has devastated mankind. To date, no approved treatment is available to completely combat this disease. Although many studies reported the potential of silver nanoparticles’ (AgNPs) action mechanism and effect against SARS-CoV-2, this is the first clinical trial that aimed to prove this effect. This open-label, randomized, parallel-group, investigator-initiated study (IIS) was conducted in India from 2021 to 2022 and included 40 patients diagnosed with moderately-severe to severe COVID-19 pneumonia. This study proved a significantly higher survival rates (p < 0.05) and significantly lower number of days until supplemental oxygenation was required (p < 0.0001) for patients receiving intravenous AgNPs in form of AgSept® in addition to the standard COVID-19 treatment. This study highlights the importance of intravenous AgNPs administration in the treatment of virus-induced pneumonia.

Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae of SARS-CoV-2 (PASC), referred to as "Long-COVID," characterized by persistent physical and mental fatigue. However, the exact pathogenetic mechanisms affecting the brain are still not well-understood. There is increasing evidence of neurovascular inflammation in the brain. However, the precise role of the neuroinflammatory response that contributes to the disease severity of COVID-19 and long COVID pathogenesis is not clearly understood. Here, we review the reports that the SARS-CoV-2 spike protein can cause blood-brain barrier (BBB) dysfunction and damage neurons either directly, or via activation of brain mast cells and microglia and the release of various neuroinflammatory molecules. Moreover, we provide recent evidence that the novel flavanol eriodictyol is particularly suited for development as an effective treatment alone or together with oleuropein and sulforaphane (ViralProtek®), all of which have potent anti-viral and anti-inflammatory actions.

Efficacy, Safety and Immunogenicity of Anti-SARS-CoV-2 Vaccines in Patients with Cirrhosis: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), has led to a pandemic with more than 6.5 million deaths worldwide. Patients with liver cirrhosis (PWLC) are regarded as prone to severe COVID-19. Vaccination against SARS-CoV-2 has been proven to be the most effective measure against COVID-19 and a variety of different vaccines have been approved for use; namely mRNA and vector-based, inactivated, whole virion, and protein subunit vaccines. Unfortunately, only a small number of PWLC were included in phase I-III vaccine trials, raising concerns regarding their efficacy and safety in this population. The authors, in this review, present available data regarding safety and efficacy of anti-SARS-CoV-2 vaccination in PWLC and discuss post-vaccination antibody responses. Overall, all vaccines seem to be extremely safe, with only a few and insignificant adverse events, and efficient, leading to lower rates of hospitalization and COVID-19-related mortality. T- and B-cell responses, on the other hand, remain an enigma, especially in patients with decompensated disease, since these patients show lower titers of anti-SARS-CoV-2 antibodies in some studies, with a more rapid waning. However, this finding is not consistent, and its clinical impact is still undetermined.

COVID-19: A trigger of autoimmune diseases.

The SARS-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), has spread worldwide and caused a global health emergency. SARS-CoV-2 is a coronaviridae virus that infects target cells by interacting with the plasma membrane-expressed angiotensin-converting enzyme 2 (ACE2) via the S1 component of the S protein. Effective host immune response to SARS-CoV-2 infection, which includes both innate and adaptive immunity, is critical for virus management and elimination. The intensity and outcome of COVID-19 may be related to an overabundance of pro-inflammatory cytokines, which results in a "cytokine storm" and acute respiratory distress syndrome. After SARS-CoV-2 infection, the immune system's hyperactivity and production of autoantibodies may result in autoimmune diseases such as autoimmune hemolytic anemia, autoimmune thrombocytopenia, Guillain-Barré syndrome, vasculitis, multiple sclerosis, pro-thrombotic state, and diffuse coagulopathy, as well as certain autoinflammatory conditions such as Kawasaki disease in children. We have reviewed the association between COVID-19 and autoimmune disorders in this article.