Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Proceedings of the National Academy of Sciences of the United States of America ; 120(5):e2212577120, 2023.
Article in English | MEDLINE | ID: covidwho-2212235

ABSTRACT

SARS-CoV-2 spike requires proteolytic processing for viral entry. A polybasic furin-cleavage site (FCS) in spike, and evolution toward an optimized FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmission. Here we show interferon-inducible restriction factors Guanylate-binding proteins (GBP) 2 and 5 interfere with furin-mediated spike cleavage and inhibit the infectivity of early-lineage isolates Wuhan-Hu-1 and VIC. By contrast, VOCs Alpha and Delta escape restriction by GBP2/5 that we map to the spike substitution D614G present in these VOCs. Despite inhibition of spike cleavage, these viruses remained sensitive to plasma membrane IFITM1, but not endosomal IFITM2 and 3, consistent with a preference for TMPRSS2-dependent plasma membrane entry. Strikingly, we find that Omicron is unique among VOCs, being sensitive to restriction factors GBP2/5, and also IFITM1, 2, and 3. Using chimeric spike mutants, we map the Omicron phenotype and show that the S1 domain determines Omicron's sensitivity to GBP2/5, whereas the S2' domain determines its sensitivity to endosomal IFITM2/3 and preferential use of TMPRSS2-independent entry. We propose that evolution of SARS-CoV-2 for the D614G substitution has allowed for escape from GBP restriction factors, but the selective pressures on Omicron for spike changes that mediate antibody escape, and altered tropism, have come at the expense of increased sensitivity to innate immune restriction factors that target virus entry.

2.
British Journal of Haematology ; 197(SUPPL 1):177-178, 2022.
Article in English | EMBASE | ID: covidwho-1861262

ABSTRACT

Background: Convalescent plasma therapy has gained worldwide attention since its inception as a soul therapy for critically ill COVID-19 patients. This study sought to ascertain survivors'knowledge, attitudes and practice about plasma donation. Methodology: In Rawalpindi, Pakistan, a cross-sectional study was conducted in COVID-19 recovered patients. Simple random sampling was used to choose 383 people. The data collection instrument was a prestructured online questionnaire. SPSS version 26 was used to enter and analyse the data. Binomial and multinomial logistic regression were used. Results: Two hundred and twenty-three (58.2%) and 326 (85.1%) of 383 individuals had sufficient knowledge and a favourable attitude towards plasma donation respectively. In 109 (28.5%) of the participants, plasma donation practice was seen. People with graduate (AOR = 5.30, p < 0.05) and postgraduate level education (7.75, p < 0.05) were found to have significantly higher knowledge as compared to people with secondary school as the highest level of education. Plasma donation practice was shown to be strongly related with plasma donation knowledge (AOR = 3.78, p < 0.001) and attitude (AOR = 4.48, p < 0.05). Conclusion: Despite the fact that the majority of people had a positive outlook and were well-informed, plasma donation was rare. The lower practice was associated with trepidation of contracting a health issue.

4.
American Journal of Gastroenterology ; 116(SUPPL):S1374, 2021.
Article in English | EMBASE | ID: covidwho-1534877

ABSTRACT

Introduction: Patients greater than 65 years old (yo) represent up to 30% of all Ulcerative colitis (UC) patients. A few studies in this population have shown poor outcomes with higher rates of infection, neoplasm, hospitalization, and mortality. However, no robust data exist on the use of biologics in the elderly population with UC. We present a retrospective analysis from 2010 to 2020 comparing outcomes such as mortality, adverse events, hospitalizations, and remission of moderate to severe UC patients 65 yo or more (≥) to those less than (<) 65 yo prescribed biologics. Methods: Data was gathered retrospectively from January 2010 to December 2020. Cohorts consisted of patients ≥18 yo with UC and no other co-existing autoimmune disease who were prescribed, biologic agents. Patient demographics were summarized as mean or proportions (%). Outcomes of interest were compared between groups according to age cutoff (≥65 yo vs , 65 yo) with the use of Pearson's chi-square or Fisher's exact test as appropriate. Multivariate analysis was conducted using logistic regression to identify independent variables associated with any of the outcomes of interest in both age groups. Results: 133 patients were included. The patient's baseline demographic characteristics were not found to be statistically significant (Table). Composite infection (18% vs 9%), skin adverse events (37% vs 32%), neoplasm (19% vs 2%), and mortality (6% vs 2%) between groups (≥ 65 yo vs <65 yo) were not statistically significant (P=0.38, P=0.70, P=0.11, P=0.48;respectively). Hospitalization and remission at 1, 3, and more than 5 years from biologics prescription were not statistically significant. However, age-stratified infections for pneumonia (PNA/COVID) resulted in statistical significance in those ≥80 yo (p<0.05). Multivariate analysis revealed that higher numbers of prescribed biologics since UC diagnosis were associated more with death (P=0.013) and neoplasm (P=0.046) in patients ≥65 yo. Conclusion: Age was not found to be an independent variable associated with any poor outcomes. Death and neoplasm events were associated with a greater number of prescribed biologics in those ≥ 65 yo and may reflect refractory versus longer disease course. Studies with larger samples of patients greater than 80 yo are required to confirm the association between PNA in this cohort. However, COVID was the etiology of the PNA. No difference in efficacy regarding remission, re-admission, or flare events was found between groups..

5.
American Journal of Gastroenterology ; 116(SUPPL):S1366-S1367, 2021.
Article in English | EMBASE | ID: covidwho-1534874

ABSTRACT

Introduction: There is limited literature available regarding the safety and efficacy of biological agents in Crohn's disease for patients aged 65 years old (yo) or greater (≥65). Existing knowledge from other autoimmune diseases regarding the initiation and maintenance of biologics in these patients has created skepticism given the potential risk of poor outcomes and mortality. We present a retrospective analysis of mortality, adverse events, rates of hospitalization, and remission in this vulnerable population compared with younger patients (<65 yo). Methods: Data was gathered retrospectively from January 2010 to December 2020. Cohorts consisted of patients ≥ 18 yo with Crohn's disease and no other co-existing autoimmune disease who were prescribed biologics agents. Patient demographics were summarized as mean or proportions (%). Outcomes of interest were compared between groups according to age cutoff (≥ 65 yo vs <65 yo) with the use of Pearson's chi-square or Fisher's exact test as appropriate. Multivariate analysis was conducted using logistic regression to identify independent variables associated with any of the outcomes of interest in both age groups. Results: 82 patients were included. Baseline demographic characteristics were similar between both groups (Table 1). Infection (30% vs 22%;P=0.63), mortality (10% vs 0%;P=0.34), and neoplasm events (0% vs 3%;P=0.15) did not reach statistical significance. Remission and hospitalization at the 1,3, 5-year endpoint after biologic prescription were similar (p>0.05). Age stratification revealed those greater than 70 yo had higher intraabdominal (IA) infections (p<0.01), whereas 65-70 yo subgroup had higher occurrence of skin abscess and rash (p<0.01). Mild skin adverse events (itching) along with mortality (N=1;COVID/Pneumonia) were higher in the 75-80 yo subgroup (p <0.01). Conclusion: In a diverse multicultural population treated with biologic agents, the occurrence of infection, neoplasm, and skin adverse events were similar in both groups. Intraabdominal infection was associated with viral and bacterial diarrhea (not clostridium difficile) when ≥70 yo. On the other hand, rash and skin abscesses were predominant in those aged 65-70 yo and itching in those 75-80 yo. Efficacy (readmission or remission) does not change despite the age group. Safety when age ≥65 yo is not guaranteed and clinical judgment should be used in each case. Larger studies in these affected age subgroups may be beneficial in understanding the clinical significance..

6.
Annals of King Edward Medical University Lahore Pakistan ; 27(1):146-149, 2021.
Article in English | Web of Science | ID: covidwho-1353208

ABSTRACT

The first outbreak of COVID-19 was reported in December 2019 in Wuhan, China and it was declared as a global pandemic on March 11, 2020. To cope with the high infectivity and increasing number of deaths associated with this disease, the healthcare resources of nearly all countries were directed to put measures in place to manage this disease. As a result, many other services including lung cancer care have been adversely affected as treatments have been delayed. The widespread lockdowns and advice to stay at home especially with common symptoms of cough has resulted in late presentations and possible upstaging of lung cancer. Owing to this similarity of symptoms and pressures faced by respiratory community to manage COVID-19 pandemic, the lung cancer patients will encounter delays in their management leading to untoward effects on their survival and quality of lives. According to an estimate, the impact of COVID-19 could lead to an additional 1372 deaths due to lung cancer in the United Kingdom alone. There has also been reluctance among the oncology community to treat patients with systemic anticancer agents due to fear of patients catching COVID-19 infection. There should be a balance between the risks and benefits of providing cancer services during this pandemic and every step should be taken to minimize delays faced by patients with lung cancer.

7.
Journal of General Internal Medicine ; 36(SUPPL 1):S258-S259, 2021.
Article in English | Web of Science | ID: covidwho-1349103
SELECTION OF CITATIONS
SEARCH DETAIL