Role of available COVID-19 vaccines in reducing deaths and perspective for next generation vaccines and therapies to counter emerging viral variants: an update.

The COVID-19 disease wreaked havoc all over the world causing more than 6 million deaths out of over 519 million confirmed cases. It not only disturbed the human race health-wise but also caused huge economic losses and social disturbances. The utmost urgency to counter pandemic was to develop effective vaccines as well as treatments that could reduce the incidences of infection, hospitalization and deaths. The most known vaccines that could help in managing these parameters are Oxford-AstraZeneca (AZD1222), Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) and Johnson & Johnson (Ad26.COV2.S). The effectiveness of AZD1222 vaccine in reducing deaths is 88% in the age group 40-59 years, touching 100% in the age group 16-44 years & 65-84 years. BNT162b2 vaccine also did well in reducing deaths due to COVID-19 (95% in the age group 40-49 years and 100% in the age group 16-44 years. Similarly, mRNA-1273 vaccine showed potential in reducing COVID-19 deaths with effectiveness ranging from 80.3 to 100% depending upon age group of the vaccinated individuals. Ad26.COV2.S vaccine was also 100% effective in reducing COVID-19 deaths. The SARS-CoV-2 emerging variants have emphasized the need of booster vaccine doses to enhance protective immunity in vaccinated individuals. Additionally, therapeutic effectiveness of Molnupiravir, Paxlovid and Evusheld are also providing resistance against the spread of COVID-19 disease as well as may be effective against emerging variants. This review highlights the progress in developing COVID-19 vaccines, their protective efficacies, advances being made to design more efficacious vaccines, and presents an overview on advancements in developing potent drugs and monoclonal antibodies for countering COVID-19 and emerging variants of SARS-CoV-2 including the most recently emerged and highly mutated Omicron variant.

Serological response after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy: a monocentric case-control study.

BACKGROUND: Inflammatory Bowel Disease (IBD) patients on biological therapy are receiving vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, it is unclear if IBD therapy could influence the response to this vaccine. In a case-control study, we assessed the antibody profiling after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy. METHODS: We analyzed seroprevalence and antibody titer, after 14 weeks from the first BNT162b2 vaccine dose, in IBD patients on biological therapy and Health Care Workers (HCWs). In IBD patients, medical history and disease data were recorded. RESULTS: Eighty-two subjects were enrolled in this study. Among them, 40 were IBD patients on biological therapy and 42 were HCWs. All subjects developed an IgG anti-Spike antibody titer above the cut-off. IBD patients on biological therapy developed a lower antibody titer than HCWs (P < 0.00001). No differences were reported in patients who received at least one dose of the vaccine within a period of 7 days from the last biological drug administration, compared to all other IBD patients. A difference was found between patients who were on concomitant immunosuppressive therapy and patients on sole biological therapy (P = 0.0287). Patients with presence of any sign of disease activity (clinical, endoscopic or laboratory) showed a higher development of antibody titer compared to those in complete disease remission (P = 0,0468). CONCLUSIONS: Our data indicate that in IBD patients, treatment with biological therapies do not affect the seroprevalence but leads to a lower antibody titer development after anti-SARS-CoV-2 BNT162b2 vaccine.

COVID-19 and the enteric system: rapidly propagating issues.

The newly described SARS-CoV-2 respiratory virus is now righteously presenting as an ominous threat, based on the speed with which it originated a zoonosis from bats; advancing at a similar rate, the virus has placed mankind before a pandemic, with an infection toll of some 431 million, and a lethality of 5,9 million (as of 25 February 2022). The size of the harm that this agent can unleash against us is appallingly wide, from brain ischemia to foot chilblain, passing by heart massive infarction. Designing a possible response, we reappraised the well-known equation depression-inflammation, and tested the hypothesis that an upgraded ease-of-mind might help reduce the host's hospitality towards SARS-CoV-2. With time passing, it becomes increasingly evident that the virus shall tend to progressively occupy spaces, replacing pandemics with an apparently calm endemicity. This will have to be avoided, and surveillance of society on psychological terms will be one tenet. Needless to say, the role of the enteric tract in these issues is growing higher, and it will be narrated to seal the matters with the last (not the least) touch of glue.

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection and severe abdominal syndrome: the Lviv "OHMATDYT" (Western Ukraine) experience.

Multisystem inflammatory syndrome in children (MIS-C) associated with Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) usually develops 1-1.5 months after mild or asymptomatic COVID-19 in countries with high incidence. MIS-C has a polymorphism of clinical manifestations, which include prolonged fever, polymorphic rash, non-purulent conjunctivitis, pneumonia complicated by distress syndrome, myocarditis, coronary artery disease, toxic shock syndrome, limb edema, polyserositis, severe abdominal syndrome with diarrhea and others. Establishing this diagnosis requires significant efforts to rule out diseases of other etiology. The aim of our study was to analyze the clinical and laboratory features of children with MIS-C associated with SARS-CoV-2 and severe abdominal syndrome. Six children with MIS-C associated with SARS-CoV-2 and severe abdominal syndrome were hospitalized in Lviv Regional Children's Clinical Hospital "OHMATDYT", Ukraine, from April 2020 to September 2021. For differential diagnosis IgM, IgG to SARS-CoV-2 by ELISA, RNA to SARS-CoV-2 by PCR, bacteriological tests of blood, urine and feces were performed. Furthermore, the diagnostic work up included chest radiography, echocardiography, ultrasound of the lungs and abdominal organs. Laboratory findings revealed an increase in the normal value of inflammatory markers and high levels of IgG to SARS-CoV-2. Administration of intravenous immunoglobulin at a dose of 1 to 2 g/kg body weight per day prevented further coronary artery disease in patients and provided regression in already affected coronary arteries. At the same time, regression of abdominal syndrome was observed. Early diagnosis of MIS-C in patients with SARS-CoV-2 and severe abdominal syndrome allows to define the appropriate treatment strategy.

Cytokine profile in patients with osteoarthritis after SARS-CoV-2 infection

BACKGROUND: Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) іnfection induces a pro-inflammatory state of an organism with long-term systemic consequences as a result. Systemic inflammation, characterized by a high circulating level of inflammatory cytokines, is a significant factor influencing articular cartilage metabolism in osteoarthritis (OA). This study aimed to determine the levels of pro-inflammatory and anti-inflammatory cytokines in plasma of patients with OA following SARS-CoV-2 infection and to compare them with those of healthy controls. METHODS: The experiment involved patients of the Orthopedic Specialty Clinic aged 46 to 69 diagnosed with knee OA. Among persons with joint pathology a group of convalescent patients from 6-9 months after COVID-19 was identified. The control group involved relatively healthy donors. The plasma levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-12β, tumor necrosis factor α [TNF-α], interferon-gamma [IFN-γ]) and anti-inflammatory (IL-4 and IL-10) cytokines were determined by enzyme-linked immunosorbent assay. RESULTS: It was established that in patients with OA, as well as after suffering from SARS-CoV-2 infection, an increase in the plasma levels of IL-1β was observed against the background of a decrease in the levels of IL-4, IL-8, IL-10, IL- 12β, TNF-α and IFN-γ, compared to the healthy controls. COVID-19 more significantly influenced the plasma levels of pro-inflammatory cytokines IL-1β and IL-12β. CONCLUSIONS: The results indicate the imbalance of pro- and anti-inflammatory cytokines in the plasma in patients with OA for a long post- COVID. Сhanges in the levels of inflammatory mediators suggest distinct immunoregulatory mechanisms involved in the pathogenesis of both joint pathology and systemic disorders caused by SARS-CoV-2. [ FROM AUTHOR]

Expression of SARS-Cov-2 Entry Factors in Patients with Chronic Hepatitis.

Chronic hepatitis (CH) of dysmetabolic or viral etiology has been associated with poor prognosis in patients who experienced the severe acute respiratory coronavirus virus-2 (SARS-Cov-2) infection. We aimed to explore the impact of SARS-Cov-2 infection on disease severity in a group of patients with CH. Forty-two patients with CH of different etiology were enrolled (median age, 56 years; male gender, 59%). ACE2 and TMPRSS2 were measured in plasma samples of all patients by ELISA and in the liver tissue of a subgroup of 15 patients by Western blot. Overall, 13 patients (31%) experienced SARS-Cov-2 infection: 2/15 (15%) had CHB, 5/12 (39%) had CHC, and 6/15 (46%) had non-alcoholic fatty liver disease (NAFLD). Compared to viral CH patients, NAFLD subjects showed higher circulating ACE2 levels (p = 0.0019). Similarly, hepatic expression of ACE2 was higher in subjects who underwent SARS-Cov-2 infection compared to the counterpart, (3.24 ± 1.49 vs. 1.49 ± 1.32, p = 0.032). Conversely, hepatic TMPRSS2 was significantly lower in patients who experienced symptomatic COVID-19 disease compared to asymptomatic patients (p = 0.0038). Further studies are necessary to understand the impact of COVID-19 in patients with pre-existing liver diseases.

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

SARS-CoV-2, alcohol consumption and liver injury.

Angiotensin converting enzyme 2 (ACE2) receptor sites for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), responsible for the disease called COVID-19 are present in the liver, especially in correspondence with cholangiocytes. Liver damage during SARS-CoV-2 infection can be due to several mechanism including direct cytopathic effect, synergy of intestinal damage/liver damage (lipopolysaccharides/Kupfer and other cells interaction), uncontrolled immune reaction (lymphopenia and significant increase in C reactive protein, ferritin, lactate dehydrogenase, D-dimer, interleukin (IL)-6, IL- 10, IL-2, interferon-gamma, etc.), sepsis, drug-induced liver injury, hypoxia and thromboembolic events. An increase in aspartate aminotransferase (AST) from 14 to 58% and alanine transaminase (ALT) from 21 to 76% has been reported. The mean level of AST and ALT has been reported to be higher in patients admitted to the intensive care unit than in those hospitalized in the ordinary hospital unit. The correlation of liver damage with worse prognosis is now a known fact, confirmed by numerous studies, in all pandemic phases. The consumption of alcohol reduces both innate and acquired immune activity and it has been hypothesized that this habit is correlated with liver increase of ACE2 receptors. Furthermore, nonalcoholic and alcoholic steatosis/steatohepatitis is a breeding ground for the development of oxidative stress. In this context, any encounter with SARS-CoV-2 infection can support and aggravate the systemic cytokine tsunami.

Covid-19 and alcohol consumption: recommendations in the Omicron era.

BACHGROUND: In the early stages of the pandemic, the first reports began that alcohol consumption could increase the risk of becoming infected and worsening the prognosis disease. This is for two reasons: behavioral and socio-economic factors that characterize a part of this population can be the cause of viral spread and a direct or indirect negative action of ethanol on the immune system. METHODS: The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before March 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines / position papers of the Italian Society on Alcohol and of the World Health Organization. RESULTS: It has been confirmed that AC is in COVID-19 era a risky behavior and that AUD and substance use disorder (SUD) patients are certainly at greater risk of contracting infection and also of having a worse course. CONCLUSIONS: In light of what has been said recommendations can be made: correctly inform the general population that AC negatively interacts with COVID-19 infection; reducing the COVID-19 risk by advocating healthy lifestyle habits (smoke, diet, physical exercise, etc) and preferential policies in population with comorbidities; implement actions that reduce the average consumption of alcohol by avoiding hazardous/harmful consumption. Abstension is better; identify alcohol consumption through a more in-depth alcohol history, using the AUDIT; AUDs patients are frail patients deserving a complete vaccination course; suggest a period of alcoholic abstention of at least thirty days before vaccination to be maintained for the following fifteen days; promoting health education campaigns for young people in order to promote vaccination culture and correct lifestyles.

Trends in the Comprehension and Management of Gastrointestinal Tract Disorders.

During the last decade, relevant advances have been made in the knowledge of the pathogenetic mechanisms of gastrointestinal (GI) tract disorders [...].

Acute-on-chronic liver failure by SARS-CoV-2 in active alcohol use disorder cirrhotic patient.

World Gastroenterology Organization define acute on chronic liver failure (ACLF) a syndrome in patients with chronic liver disease with or without previously diagnosed cirrhosis, characterized by acute hepatic decompensation resulting in liver failure and one or more extrahepatic organ failures, associated with increased mortality up to three months. A-56-year-old gentleman with alcohol related liver cirrhosis (ARLC) and history of variceal bleeding with insertion of transjugular intrahepatic porto-systemic stent shunt presented with two days history of fever, dry cough and worsening of the sensory. The severe acute respiratory coronavirus-2 (SARS-CoV-2) nasopharingeal C-reactive protein test was positive. X-ray showed multiple patchy ground glass opacities in both lungs. Despite the therapy, the clinical and laboratory picture deteriorated rapidly. The patient succumbed on day 14 with multi-organ-failure. SARS-Cov-2 infection can overlap with pre-existing chronic liver disease or induce liver damage directly or indirectly. From the data of the literature and from what is inferred from the case report it clearly emerges that alcohol related liver disease (ALD) patients are particularly vulnerable to SARS-Cov-2 infection. Thereafter, some considerations can be deduced from the analysis of the case report. In subjects with pre-existing cirrhosis hepatologists should play more attention to hepatic injury and monitor risk of hepatic failure caused by coronavirus disease 2019 (COVID-19). It is appropriate to promptly define the alcoholic etiology and investigate whether the patient is actively consuming. In fact, withdrawal symptoms may be present, and the prognosis of these patients is also worse. Physicians should be alerted to the possibility of the development of ACLF in this population, hepatotoxic drugs should be avoided, it is recommended to use of hepatoprotective therapy to mitigate the negative impact of COVID-19, and it is mandatory to administer anti COVID-19 vaccine to patients with alcohol related liver cirrhosis.