Temporal trends and characteristics associated with racial, ethnic, and sex representation in COVID-19 clinical trials: A systematic review and meta-analysis.

BACKGROUND: Early in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear. METHODS: PubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021-2022. Meta-regression was performed to assess associations between trial characteristics and group representation. RESULTS: We retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%-67.3%]; 2021-2022: 73.8% [95% CI, 71.5%-76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%-47.4%)]; 2021-2022: 51.1% [95% CI, 49.3%-52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03-0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08-0.25]) and lower Asian (coefficient, -0.03 [95% CI, -0.06- -0.003]) and female representation (coefficient, -0.03 [95% CI, -0.07- -0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13-0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13-0.18]), and lower Black representation (coefficient, -0.10 [95% CI, -0.10- -0.08]). CONCLUSIONS: Despite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity.

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.

In Enterobacterales bacteremia, antipseudomonal ß-lactam de-escalation was noninferior to continuation for clinical cure at 3 to 5 d.

SOURCE CITATION: López-Cortés LE, Delgado-Valverde M, Moreno-Mellado E, et al; SIMPLIFY study group. Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial. Lancet Infect Dis. 2024;24:375-385. 38215770.

In adults with post-COVID-19 conditions, a synbiotic preparation, SIM01, alleviated some symptoms at 6 mo.

SOURCE CITATION: Lau RI, Su Q, Lau IS, et al. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2024;24:256-265. 38071990.

Public interest trends for COVID-19 and pandemic trajectory: A time-series analysis of US state-level data.

Google Trends provides spatiotemporal data for user-specific terms scaled from less than 1 (lowest relative popularity) to 100 (highest relative popularity) as a proxy for the public interest. Here we use US state-level data for COVID-19 to examine popularity trends during the pandemic evolution. We used "coronavirus" and "covid" search terms and set the period up from January 1st, 2020, to November 12, 2022. We measured the agreement on web rankings between states using the nonparametric Kendall's W (0 for no concordance to 1 for perfect agreement). We compiled state-level weekly data on COVID-19 incidence and mortality and scaled state curves from 0 to 100 through a min-max normalization process. We used a dynamic time-warping algorithm to calculate similarities between the popularity, mortality, and incidence of COVID-19. The methodology is a pattern recognition process between time series by distance optimization. The similarity was mapped from 0 to 1, with 1 indicating perfect similarity and 0 indicating no similarity. The peak in popularity was in March 2020, succeeded by a decline and a prolonged period of fluctuation around 20%. Public interest rose briefly at the end of 2021, to fall to a low activity of around 10%. This pattern was remarkably consistent across states (Kendal's W 0.94, p < 0.001). Web search trends were an impression of contagion growth: Overall, popularity-mortality trajectories yielded higher similarity indices (median 0.78; interquartile range 0.75-0.82) compared to popularity-incidence trajectories (median 0.74; interquartile range 0.72-0.76, Wilcoxon's exact p<0.001). The popularity-mortality trajectories had a very strong similarity (>0.80) in 19/51 (37%) regions, as opposed to only 4/51 (8%) for popularity-incidence trajectories. State-level data show a fading public concern about COVID-19, and web-search popularity patterns may reflect the COVID-19 trajectory in terms of cases and mortality.

Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.

Prevalence of Steatotic Liver Disease Among US Adults with Rheumatoid Arthritis.

BACKGROUND: The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown. AIMS: To investigate the prevalence of SLD and liver fibrosis among patients with RA. METHODS: We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02-47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89-23.07%) and 10.35% (95% CI: 5.55-18.48%), respectively. BMI ≥ 30 kg/m2, (aOR 6.23; 95% CI: 1.95-19.88), diabetes (aOR 5.90; 95% CI: 1.94-17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12-7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69-79.70) was also independently associated with high-risk NASH. CONCLUSIONS: The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD.

Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.

OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life. SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews. PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed. PRIMARY AND SECONDARY OUTCOMES: Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model. RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months. CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

Cumulative incidence and mortality rate of cardiovascular complications due to laboratory-confirmed influenza virus infection: A systematic review and meta-analysis.

Influenza infection is associated with cardiovascular complications that range significantly in presentation and severity. The cumulative incidence of cardiovascular complications due to laboratory-confirmed influenza, however, is not reported in the literature. We conducted a systematic review and random-effects meta-analysis to evaluate the cumulative incidence and mortality rate of influenza virus-related cardiovascular complications in hospitalized patients. We searched the PubMed and EMBASE databases for studies reporting acute myocardial infarction (AMI), heart failure (HF), arrhythmia of any kind, stroke or transient ischemic attack (TIA), and myocarditis in hospitalized patients with laboratory-confirmed influenza virus infection. Prospective studies, retrospective cohort studies, and randomized controlled trials (RCTs) were included in the analysis. We followed the PRISMA checklist and used 95% confidence intervals (CIs) to report meta-analysis outcomes. This study was registered on PROSPERO (CRD42023427849). After retrieving 2803 studies, we identified 19 studies (18 observational and 1 RCT) with relevant data, and we included 6936 patients in our analysis, of whom 690 (9.9%) developed a cardiovascular outcome of interest. The cumulative incidence of HF was 17.47% (95% CI: 5.06%-34.54%), arrhythmia of any kind 6.12% (95% CI: 0.00%-21.92%), myocarditis 2.56% (95% CI: 0.66%-5.38%), AMI 2.19% (95% CI: 1.03%-3.72%), and stroke or TIA 1.14% (95% CI: 0.00%-4.05%). The in-hospital mortality rate from cardiovascular events was 1.38% (95% CI: 0.00%-4.80%). Cardiovascular complications occur in patients with influenza virus infection, with the cumulative incidence of specific cardiac manifestations varying considerably (1.51%-17.47%). Preventive strategies and close clinical monitoring after infection remain a priority.

A Methylazanediyl Bisacetamide Derivative Sensitizes Staphylococcus aureus Persisters to a Combination of Gentamicin And Daptomycin.

Infections caused by Staphylococcus aureus, notably methicillin-resistant S. aureus (MRSA), pose treatment challenges due to its ability to tolerate antibiotics and develop antibiotic resistance. The former, a mechanism independent of genetic changes, allows bacteria to withstand antibiotics by altering metabolic processes. Here, a potent methylazanediyl bisacetamide derivative, MB6, is described, which selectively targets MRSA membranes over mammalian membranes without observable resistance development. Although MB6 is effective against growing MRSA cells, its antimicrobial activity against MRSA persisters is limited. Nevertheless, MB6 significantly potentiates the bactericidal activity of gentamicin against MRSA persisters by facilitating gentamicin uptake. In addition, MB6 in combination with daptomycin exhibits enhanced anti-persister activity through mutual reinforcement of their membrane-disrupting activities. Crucially, the "triple" combination of MB6, gentamicin, and daptomycin exhibits a marked enhancement in the killing of MRSA persisters compared to individual components or any double combinations. These findings underscore the potential of MB6 to function as a potent and selective membrane-active antimicrobial adjuvant to enhance the efficacy of existing antibiotics against persister cells. The molecular mechanisms of MB6 elucidated in this study provide valuable insights for designing anti-persister adjuvants and for developing new antimicrobial combination strategies to overcome the current limitations of antibiotic treatments.

Association of the Streptococcus bovis/Streptococcus equinus Complex With Colorectal Neoplasia: A Systematic Review and Meta-analysis.

Background: Invasive infection with Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature. Methods: We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia. Results: We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25). Conclusions: Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.

Prevalence and risk factors of nonalcoholic fatty liver disease, high-risk nonalcoholic steatohepatitis, and fibrosis among lean United States adults: NHANES 2017-2020.

Background: Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern worldwide. Early detection and management of modifiable risk factors are critical to mitigating its impact. This study aimed to investigate the prevalence and risk factors of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis among lean adults in the United States (US), using the latest National Health and Nutrition Examination Survey (NHANES) dataset from 2017-2020. Methods: Using controlled attenuation parameter scores of ≥285 dB/m, we assessed the age-adjusted prevalence of lean NAFLD. To determine the age-adjusted prevalence of high-risk NASH and significant fibrosis, we used the FibroScan-aspartate aminotransferase (FAST) score (cutoffs 0.35 and 0.67) and vibration-controlled transient elastography (liver stiffness measurement ≥8 kPa). Multivariate logistic regression was used to identify potential risk factors. Results: We found the age-adjusted prevalence of lean NAFLD to be 6.30%. Among lean US adults, the age-adjusted prevalence of high-risk NASH and significant fibrosis was 1.29% and 4.35%, respectively. Older age and metabolic comorbidities, such as hypertension, diabetes, and dyslipidemia were associated with NAFLD and its complications. Conclusion: These findings suggest that the prevalence of NAFLD is of concern among lean individuals, particularly those aged 40 and older with metabolic comorbidities, while a targeted approach to screening and risk stratification for hepatic fibrosis upon lean NAFLD diagnosis is warranted.

Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020.

Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD).1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g).1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD).1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States.

In older adults, an AS01E-adjuvanted RSVPreF3 OA vaccine reduced RSV-related lower respiratory tract disease.

SOURCE CITATION: Papi A, Ison MG, Langley JM, et al; AReSVi-006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388:595-608. 36791160.

In older adults, an Ad26.RSV.preF-RSV preF protein vaccine reduced RSV-related lower respiratory tract disease.

SOURCE CITATION: Falsey AR, Williams K, Gymnopoulou E, et al; CYPRESS Investigators. Efficacy and safety of an Ad26.RSV.preF-RSV preF protein vaccine in older adults. N Engl J Med. 2023;388:609-620. 36791161.

Impact of prior HBV, HAV, and HEV infection on non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.

Public interest trends for Covid-19 and alignment with the disease trajectory: A time-series analysis of national-level data.

Data from web search engines have become a valuable adjunct in epidemiology and public health, specifically during epidemics. We aimed to explore the concordance of web search popularity for Covid-19 across 6 Western nations (United Kingdom, United States, France, Italy, Spain and Germany) and how timeline changes align with the pandemic waves, Covid-19 mortality, and incident case trajectories. We used the Google Trends tool for web-search popularity, and "Our World in Data" on Covid-19 reported cases, deaths, and administrative responses (measured by stringency index) to analyze country-level data. The Google Trends tool provides spatiotemporal data, scaled to a range of <1 (lowest relative popularity) to 100 (highest relative popularity), for the selected search terms, timeframe, and region. We used "coronavirus" and "covid" as search terms and set the timeframe up to November 12, 2022. We obtained multiple consecutive samples using the same terms to validate against sampling bias. We consolidated national-level incident cases and deaths weekly and transformed them to a range between 0 to 100 through the min-max normalization algorithm. We calculated the concordance of relative popularity rankings between regions, using the non-parametric Kendall's W, which maps concordance between 0 (lack of agreement) to 1 (perfect match). We used a dynamic time-warping algorithm to explore the similarity between Covid-19 relative popularity, mortality, and incident case trajectories. This methodology can recognize the similarity of shapes between time-series through a distance optimization process. The peak popularity was recorded on March 2020, to be followed by a decline below 20% in the subsequent three months and a long-standing period of variation around that level. At the end of 2021, public interest spiked shortly to fade away to a low level of around 10%. This pattern was highly concordant across the six regions (Kendal's W 0.88, p< .001). In dynamic time warping analysis, national-level public interest yielded a high similarity with the Covid-19 mortality trajectory (Similarity indices range 0.60-0.79). Instead, public interest was less similar with incident cases (0.50-0.76) and stringency index trajectories (0.33-0.64). We demonstrated that public interest is better intertwined with population mortality, rather than incident case trajectory and administrative responses. As the public interest in Covid-19 gradually subsides, these observations could help predict future public interest in pandemic events.