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The Lancet. Microbe May 2024Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of...
Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.
BACKGROUND
Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.
METHODS
In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery.
FINDINGS
The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors.
INTERPRETATION
Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment.
FUNDING
US National Institutes of Health.
PubMed: 38815595
DOI: 10.1016/S2666-5247(24)00015-6 -
Turkish Journal of Medical Sciences 2023It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and...
BACKGROUND/AIM
It wasaimed herein to investigate coronavirus disease (COVID-19) in cancer patients and compare hematological and solid organ cancer patients in terms of the course and outcome of this disease.
MATERIALS AND METHODS
Data from cancer patients with laboratory-confirmed COVID-19 infection were analyzed retrospectively. Risk factors for poor prognosis and the effect of vaccination on the clinical outcomes of the patients were evaluated.
RESULTS
A total of 403 cancer patients who were diagnosed with COVID-19 between March 1st, 2021, and November 30th, 2022, were included, of whom 329 (81.6%) had solid and 74 (18.4%) had hematological cancers. Hospitalization and intensive care unit (ICU) admission rates were significantly higher in the hematological cancer patients compared to the solid organ cancer patients (73.0% vs. 35.9%, p< 0.001 and 25.7% vs. 14.0%, p= 0.013, respectively). The COVID-19related case fatality rate (CFR) was defined as 15.4%, and it was higher in the hematologicalcancer patientsthan inthe solid organ cancer patients (23.0% vs. 13.7%, p= 0.045) and was higher in patients with metastatic/advanced disease compared to the other cancer stages (p< 0.001). In the solid organ cancergroup, hospitalization, ICU admission, and the COVID-19 CFR were higher in patients with respiratory and genitourinary cancers (p< 0.001). A total of 288 (71.8%) patients had receivedCOVID-19 vaccination; 164 (56.94%) had≤2 doses and 124 (43.06%) had≥3 doses. The hospitalization rate was higher in patients with ≤2 doses of vaccine compared to those with ≥3 doses (48.2% vs. 29.8%,p= 0.002). Patients with COVID-19related death had higher levels of leucocyte, neutrophil, D-dimer, troponin, C-reactive protein (CRP), procalcitonin, and ferritin and lower levels of lymphocyte than the survivors. In the logistic regression analysis,the risk of COVID-19related mortality was higher in the hematological cancer patients(OR:1.726), those who were male (OR:1.757), and with the Pre-Delta/Delta variants (OR:1.817).
CONCLUSION
This study revealed that there is an increased risk of COVID-19-related serious events (hospitalization, ICU admission, or death) in patients with hematological cancerscompared with those who have solid organ cancers. It wasalso shown that receiving ≥3 doses of COVID-19 vaccine is more protective against severe illness and the need for hospitalization than ≤2 doses.
Topics: Humans; COVID-19; Male; Female; Middle Aged; Neoplasms; Retrospective Studies; COVID-19 Vaccines; Aged; Hospitalization; Risk Factors; SARS-CoV-2; Intensive Care Units; Adult; Vaccination; Prognosis
PubMed: 38813483
DOI: 10.55730/1300-0144.5744 -
Frontiers in Public Health 2024For many infectious diseases, women are at higher risk and have a more severe disease course than men for many reasons, including biological differences, social...
INTRODUCTION
For many infectious diseases, women are at higher risk and have a more severe disease course than men for many reasons, including biological differences, social inequalities, and restrictive cultural norms. The study focuses on infections with human papillomaviruses (HPV) in the form of cervical cancer as a gender-specific disease. The main goal is to evaluate cervical tumour incidence trends in the Czech female population in the HPV vaccination period 2012-2020 in relation to selected demographic, socioeconomic, and geographic indicators.
METHODS
This is a retrospective ecological study. Data from publicly available databases about the incidence and mortality of cervical tumours (C53 Malignant neoplasm of cervix uteri, D06 Carcinoma of cervix uteri according to ICD 10) and HPV vaccination rate were analysed and compared with demographic, socioeconomic and territorial data. Associations were searched using correlation analysis.
RESULTS
There was a decreasing trend in the incidence of cervical cancer in the observed period. Regarding cervical tumours (C53, D06) and malignant neoplasm of cervix uteri incidence (C53), the decrease was approximately 11 and 20%, respectively. Differences between regions were observed in incidences and vaccination rates. Based on correlation analysis, indicators connected with urban/rural aspects, such as a share of urban population and population density, were statistically significant. The indicators related to higher cervical cancer incidence are the high unemployment rate of women, the high number of divorces, the high number of abortions, the high share of the urban population, the high number of students, and the high number of women with only primary education. On the other hand, the indicators related to lower cervical cancer incidence are the high gross domestic product (GDP), the high average gross monthly wage per employee, the high employment rate of women, the higher average age of mothers at birth, and the high number of women with tertiary education.
CONCLUSION
Results underline the problem of economically disadvantaged regions and families. Increasing vaccination rates, promoting regular screening for cervical cancer, and supporting awareness in the population, especially in regions with higher incidence rates, should be priorities for public health efforts.
Topics: Humans; Female; Uterine Cervical Neoplasms; Retrospective Studies; Incidence; Czech Republic; Adult; Socioeconomic Factors; Middle Aged; Papillomavirus Infections; Papillomavirus Vaccines; Demography; Aged; Vaccination
PubMed: 38813429
DOI: 10.3389/fpubh.2024.1347800 -
Frontiers in Oncology 2024In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies...
Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma.
BACKGROUND
In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation.
METHODS
In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x10, 4x10, or 1x10 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients.
RESULTS
GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit.
CONCLUSIONS
Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.
PubMed: 38812776
DOI: 10.3389/fonc.2024.1395978 -
Frontiers in Immunology 2024
Topics: Tumor Microenvironment; Humans; Neoplasms; Animals; Immunotherapy
PubMed: 38812517
DOI: 10.3389/fimmu.2024.1425136 -
Science Advances May 2024Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal...
Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal antibody responses. Here, we report a strategy to effectively concentrate immunogens and adjuvants in gut-draining lymph nodes (LNs) to induce gut-associated mucosal immunity. We prepared nanoemulsions (NEs) based on biodegradable oils commonly used as vaccine adjuvants, which encapsulated a potent Toll-like receptor agonist and displayed antigen conjugated to their surface. Following intraperitoneal administration, these NEs accumulated in gut-draining mesenteric LNs, priming strong germinal center responses and promoting B cell class switching to immunoglobulin A (IgA). Optimized NEs elicited 10- to 1000-fold higher antigen-specific IgG and IgA titers in the serum and feces, respectively, compared to free antigen mixed with NE, and strong neutralizing antibody titers against severe acute respiratory syndrome coronavirus 2. Thus, robust gut humoral immunity can be elicited by exploiting the unique lymphatic collection pathways of the gut with a lymph-targeting vaccine formulation.
Topics: Animals; Immunity, Humoral; Mice; Gastrointestinal Tract; Lymphoid Tissue; Immunity, Mucosal; SARS-CoV-2; COVID-19; Antibodies, Viral; Lymph Nodes; Immunoglobulin A; COVID-19 Vaccines; Antibodies, Neutralizing; Female; B-Lymphocytes; Adjuvants, Vaccine; Mice, Inbred C57BL; Humans
PubMed: 38809992
DOI: 10.1126/sciadv.adn7786 -
Asian Pacific Journal of Cancer... May 2024Mongolia faces a significant burden of cervical cancer, with the highest prevalence of Human Papillomavirus (HPV) in the region. Cervical cancer ranks as the third most...
BACKGROUND
Mongolia faces a significant burden of cervical cancer, with the highest prevalence of Human Papillomavirus (HPV) in the region. Cervical cancer ranks as the third most common cancer among women in the country. This study aimed to assess the acceptance of self-sampling among young women in Mongolia and evaluate their knowledge regarding HPV and cervical cancer.
METHODS
In this study, participants provided a self-administered vaginal swabs to detect high-risk HPV genotypes. Both acceptability of self-sampling using swabs and participants knowledge regarding HPV and cervical cancer through a scored questionnaire were assessed. The knowledge scale was categorized into three groups: low (0-2), moderate (3-4) and high (5-6).
RESULTS
A total of 203 women aged 24-28 years completed the questionnaire and provided self-administered vaginal swabs. The majority (95.1%) found self-sampling technique using Copan Self Vaginal FLOQSwabs® easy to perform. Additionally, 98.5% indicated that the self-swab instructions were clear and comprehensive, while 94.1% reported no pain during the process. Furthermore, 67.8% of participants expressed a preference for performing the swab in a clinic rather than at home. All respondents chose self-sampling due to greater personal privacy, tranquility, reduced anxiety and time optimization. The questionnaire results revealed an overall low level of knowledge about HPV among participants, with a mean score at 1.9 out of 6 [95%CI 1.67-2.21] and a moderate level of knowledge regarding cervical cancer risks, with a mean score at 3.7 out of 6 [95%CI 3.19-4.21]. This pattern was consistent across both vaccinated and unvaccinated cohorts, indicating a strong demand for enhanced awareness of HPV and cervical cancer.
CONCLUSIONS
This study demonstrates the high acceptance of self-sampling among young women aged 24-28 years in Mongolia. However, it also underscores a significant need for improved awareness initiatives concerning HPV and cervical cancer in Mongolia.
Topics: Humans; Female; Papillomavirus Infections; Adult; Mongolia; Young Adult; Health Knowledge, Attitudes, Practice; Uterine Cervical Neoplasms; Papillomaviridae; Surveys and Questionnaires; Vaginal Smears; Self Care; Follow-Up Studies; Specimen Handling; Patient Acceptance of Health Care; Prognosis; Early Detection of Cancer; Cross-Sectional Studies; Human Papillomavirus Viruses
PubMed: 38809655
DOI: 10.31557/APJCP.2024.25.5.1823 -
Asian Pacific Journal of Cancer... May 2024This study aimed to investigate the cytotoxicity effect of the ethyl acetate extract of Aaptos suberitoides on colorectal cancer cells (DLD-1) and murine fibroblast...
OBJECTIVE
This study aimed to investigate the cytotoxicity effect of the ethyl acetate extract of Aaptos suberitoides on colorectal cancer cells (DLD-1) and murine fibroblast cells (NIH-3T3).
METHODS
A. suberitoides was collected from Putus Island, Bunaken National Park, North Sulawesi, Indonesia, and was processed with maceration and ethyl acetate extraction. The sponge extract was characterized based on Thin Layer Chromatography (TLC) and then identified by using LCMS/MS analysis. DLD-1 and NIH-3T3 cells were treated with the ethyl acetate extract and then followed by 3- [4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess their cytotoxicity effect.
RESULTS
LCMS/MS analysis showed that the most abundant compounds in this extract were identified as aaptamine (1). Furthermore, this study revealed that the active ethyl acetate fraction of A. suberitoides has cytotoxic effects in colorectal cancer DLD-1 cells with an IC50 value of 9.597 µg/mL, higher than NIH-3T3 cells with an IC50 value of 12.23 µg/mL Thus, the active ethyl acetate fraction of A. suberitoides is considered more toxic to cancer cells than normal cells.
CONCLUSION
This study provides the first evidence to support the role of the ethyl acetate extract of A. suberitoides sponge extracts to be developed as a colorectal anticancer agent.
Topics: Animals; Colorectal Neoplasms; Porifera; Mice; Humans; Indonesia; Cell Proliferation; NIH 3T3 Cells; Antineoplastic Agents; Tumor Cells, Cultured; Apoptosis; Naphthyridines
PubMed: 38809646
DOI: 10.31557/APJCP.2024.25.5.1737 -
Emerging Microbes & Infections May 2024Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient...
Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. , NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct and characteristics.
PubMed: 38808613
DOI: 10.1080/22221751.2024.2362392 -
Frontiers in Public Health 2024Cervical cancer, primarily caused by human papillomavirus (HPV) infection, poses a significant global health challenge. Due to higher levels of poverty and health... (Review)
Review
Cervical cancer, primarily caused by human papillomavirus (HPV) infection, poses a significant global health challenge. Due to higher levels of poverty and health inequities, Indigenous women worldwide are more vulnerable to cervical cancer than their non-Indigenous counterparts. However, despite constituting nearly 10% of the population in Latin America and the Caribbean (LAC), the true extent of the burden of cervical cancer among Indigenous people in this region remains largely unknown. This article reviews the available information on cervical cancer incidence and mortality, as well as HPV infection prevalence, among Indigenous women in LAC. The limited existing data suggest that Indigenous women in this region face a heightened risk of cervical cancer incidence and mortality compared to non-Indigenous women. Nevertheless, a substantial knowledge gap persists that must be addressed to comprehensively assess the burden of cervical cancer among Indigenous populations, especially through enhancing cancer surveillance across LAC countries. Numerous structural, social and cultural barriers hindering Indigenous women's access to HPV vaccination and cervical cancer screening worldwide have been identified and are reviewed in this article. The discussion highlights the critical role of culturally sensitive education, community engagement, and empowerment strategies in overcoming those barriers. Drawing insights from the success of targeted strategies in certain high-income countries, the present article advocates for research, policies and healthcare interventions tailored to the unique context of LAC countries.
Topics: Humans; Uterine Cervical Neoplasms; Female; Latin America; Caribbean Region; Papillomavirus Infections; Indigenous Peoples; Incidence; Papillomavirus Vaccines; Early Detection of Cancer; Prevalence
PubMed: 38807996
DOI: 10.3389/fpubh.2024.1376748