Safety and Pharmacokinetics of Casirivimab and Imdevimab (CAS+IMD) in Pediatric Outpatients With COVID-19.

The safety of casirivimab+imdevimab (CAS+IMD) (anti-SARS-CoV-2 monoclonal antibodies [mAbs]) in pediatric outpatients with COVID-19 was evaluated in a randomized, phase 1/2/3 trial. Consistent with adults, CAS+IMD was generally well tolerated with low drug-induced immunogenicity rates. The findings support development of next-generation anti-SARS-CoV-2 mAbs for at-risk pediatric patients.

Treatment of Macrolide-resistant Mycoplasma pneumoniae Pneumonia in Children: A Meta-analysis of Macrolides Versus Tetracyclines.

BACKGROUND: The global prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia infections, particularly in children, is on the rise. It is imperative to assess the clinical efficacies of alternative antibiotics such as tetracyclines to ensure effective treatment, mitigate antibiotic resistance, enhance clinical outcomes, and minimize the spread of resistant strains among MRMP-infected children. The objective of this study was to compare the therapeutic efficacies of macrolides and tetracyclines in treating MRMP pneumonia in children. METHODS: We systematically searched the literature to identify comparative studies that examined the clinical outcomes of macrolide and tetracycline antibiotics in children with MRMP pneumonia. We conducted a meta-analysis of the mean duration of fever, hospital stay duration, therapeutic efficacies, and time to defervescence to compare macrolides and tetracyclines. RESULTS: Eleven studies involving 1143 patients compared the clinical efficacies of macrolides and tetracyclines in children with MRMP pneumonia. The studies were conducted in China, Japan, and Korea, and the outcomes of febrile days, hospital stay duration, therapeutic efficacy, and time to defervescence were analyzed. The macrolides studied were azithromycin and clarithromycin, whereas the tetracyclines included minocycline and doxycycline. The pooled estimate of 5 studies showed that the mean duration of febrile days and hospital stay was longer in the macrolides group than tetracycline group [weighted mean difference = 1.64 days, 95% confidence interval (CI): 0.68-2.59, weighted mean difference = 1.22 days, 95% CI: 0.82-1.62, respectively]. The therapeutic efficacy was significantly lower in the macrolide group than in the tetracycline group (odds ratio: 0.33, 95% CI: 0.20-0.57). CONCLUSIONS: The clinical efficacy of tetracycline treatment was superior to that of macrolide treatment in children with MRMP pneumonia. However, further research is required to validate these findings and inform evidence-based clinical practice guidelines.

Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19.

BACKGROUND: Passive administration of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs), such as CAS + IMD (Casirivimab + Imdevimab) antibody cocktail demonstrated beneficial effects on clinical outcomes in hospitalized patients with COVID-19 who were seronegative at baseline and outpatients. However, little is known about their impact on the host immunophenotypes. METHODS: We conducted an immunoprofiling study in 46 patients from a single site of a multi-site trial of CAS + IMD in hospitalized patients. We collected longitudinal samples during October 2020 âˆ¼ April 2021, prior to the emergence of the Delta and Omicron variants and the use of COVID-19 vaccines. All collected samples were analyzed without exclusion and post-hoc statistical analysis was performed. We examined the dynamic interplay of CAS + IMD with host immunity applying dimensional reduction approach on plasma proteomics and high dimensional flow cytometry data. FINDINGS: Using an unbiased clustering method, we identified unique immunophenotypes associated with acute inflammation and disease resolution. Compared to placebo group, administration of CAS + IMD accelerated the transition from an acute inflammatory immunophenotype, to a less inflammatory or "resolving" immunophenotype, as characterized by reduced tissue injury, proinflammatory markers and restored lymphocyte/monocyte imbalance independent of baseline serostatus. Moreover, CAS + IMD did not impair the magnitude or the quality of host T cell immunity against SARS-CoV-2 spike protein. INTERPRETATION: Our results identified immunophenotypic changes indicative of a possible SARS-CoV-2 neutralizing antibodies-induced anti-inflammatory effect, without an evident impairment of cellular antiviral immunity, suggesting that further studies of Mabs effects on SAS-CoV-2 or other viral mediated inflammation are warranted. FUNDING: Regeneron Pharmaceuticals Inc and federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number: HHSO100201700020C.

Evaluation of the feasibility and efficacy of point-of-care antibody tests for biomarker guided management of COVID-19.

BACKGROUND: Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. METHODS: COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. RESULTS: While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. CONCLUSIONS: Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.

Combination of a Rapid Diagnostic Assay and Antimicrobial Stewardship Intervention for Gram-Negative Bacteremia.

Background: Traditional blood cultures for gram-negative bacteremia can take up to 72 hours or more to return results, prolonging the duration of empiric broad-spectrum intravenous antibiotics. The Accelerate Pheno system provides rapid identification and susceptibilities for blood cultures in gram-negative bacteremia. Current data on its clinical utility are mixed overall, so the system requires further research. Methods: A multicenter, retrospective quasi-experimental study was conducted comparing the Accelerate Pheno rapid diagnostic system with antimicrobial stewardship intervention and traditional blood cultures alone. Results: A total of 264 patients with blood cultures with gram-negative bacteria growth were included in the final analysis (102 pre-intervention, 162 post-intervention). The antimicrobial stewardship team made 364 recommendations in 152/162 (93.8%) patients in the post group. Duration of intravenous therapy was shorter (P < .001) for the post-intervention group (median, 4.0 days) compared with the pre-intervention group (median, 7.5 days). Hospital length of stay was also shorter (P < .001) for the post-intervention group (median, 5.1 days) compared with the pre-intervention group (median, 7.0 days). Readmission rates within 30 days were reduced (P = .042) post-intervention (13.0%) compared with pre-intervention (22.6%). In the post-intervention group, a larger proportion of patients were transitioned to oral therapy at any point (126/162, 77.8%) compared with pre-intervention (62/102, 60.8%; P < .001). Conclusions: These results suggest that the Accelerate Pheno system, with active review and intervention by a multidisciplinary antimicrobial stewardship team, is a useful tool in improving both patient-centric and antimicrobial stewardship outcomes.

The symptoms evolution of long COVID­19 (SE-LC19): a new patient-reported content valid instrument.

BACKGROUND: The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID­19 (SE-LC19), and establish its content validity. METHODS: The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID. A 2-part mixed-method approach was employed. Part 1: Qualitative interviews with a purposive sample of 41 patients with confirmed long COVID were conducted for the content validation of SE-LC19. During cognitive debriefing interviews, patients were asked to describe their understanding of the instrument's instructions, specific symptoms, response options, and recall period to ensure its relevance and comprehensiveness. Five clinicians of different medical specialties who regularly treated patients with long COVID were also interviewed to obtain their clinical expert opinions on SE-LC19. Part 2: Exploratory Rasch Measurement Theory (RMT) analysis was conducted to evaluate the psychometric properties of the SE-LC19 data collected during the interviews. RESULTS: Overall, patients reported that the instructions, questions, recall period, and response options for SE-LC19 were comprehensive and relevant. Minor conceptual gaps reported by patients captured nuances in the experience of some symptoms that could be considered in future studies. Some patients suggested a revision of the recall period from 24 h to 7 days to be able to capture more symptoms given the waxing and waning nature of some symptoms. Clinicians found the instrument comprehensive with minimal suggestions regarding its content. Exploratory RMT analyses provided evidence that the SE-LC19 questionnaire performed as intended. CONCLUSION: The present mixed-methods study in patients with confirmed long COVID supports the content validity and applicability of the SE-LC19 instrument to evaluate the symptoms of patients with long COVID. Further research is warranted to explore the psychometric properties of the instrument and refine a meaningful and robust patient-relevant endpoint for use in different settings such as clinical trials and clinical practice to track the onset, severity, and recovery of long COVID.

Machine learning-assisted high-throughput screening for Anti-MRSA compounds.

BACKGROUND: Antimicrobial resistance is a major public health threat, and new agents are needed. Computational approaches have been proposed to reduce the cost and time needed for compound screening. AIMS: A machine learning (ML) model was developed for the in silico screening of low molecular weight molecules. METHODS: We used the results of a high-throughput Caenorhabditis elegans methicillin-resistant Staphylococcus aureus (MRSA) liquid infection assay to develop ML models for compound prioritization and quality control. RESULTS: The compound prioritization model achieved an AUC of 0.795 with a sensitivity of 81% and a specificity of 70%. When applied to a validation set of 22,768 compounds, the model identified 81% of the active compounds identified by high-throughput screening (HTS) among only 30.6% of the total 22,768 compounds, resulting in a 2.67-fold increase in hit rate. When we retrained the model on all the compounds of the HTS dataset, it further identified 45 discordant molecules classified as non-hits by the HTS, with 42/45 (93%) having known antimicrobial activity. CONCLUSION: Our ML approach can be used to increase HTS efficiency by reducing the number of compounds that need to be physically screened and identifying potential missed hits, making HTS more accessible and reducing barriers to entry.

Cumulative incidence and risk of infection in patients with rheumatoid arthritis treated with janus kinase inhibitors: A systematic review and meta-analysis.

Patients with rheumatoid arthritis (RA) who receive immunosuppressive medications have a heightened risk of infection. The goal of our study was to calculate the pooled cumulative incidence and risk of infection in patients with RA treated with Janus kinase inhibitors (JAKi). The PubMed and EMBASE databases were queried for randomized controlled trials comparing patients with RA treated with JAKi (upadacitinib, baricitinib, tofacitinib, peficitinib, or filgotinib), defined as the treatment group, compared with control subjects, defined as participants receiving placebo or treatment regimen that was similar to that of participants in the treatment group, with the exception of JAKi. The primary study endpoint was the relative risk (RR) of any-grade and severe infection. The secondary endpoints were RR and cumulative incidence of opportunistic infections, herpes zoster, and pneumonia. The Stata v17 software was used for all data analysis. Results showed that treatment with baricitinib was associated with an increased risk of any-grade (RR 1.34; 95% CI: 1.19-1.52) and opportunistic (RR 2.69; 95% CI: 1.22-5.94) infection, whereas treatment with filgotinib (RR 1.21; 95% CI: 1.05-1.39), peficitinib (RR 1.40; 95% CI: 1.05-1.86) and upadacitinib (RR 1.30; 95% CI: 1.09-1.56) was associated with increased risk of any-grade infection only. Analysis based on type of infection showed a pooled cumulative incidence of 32.44% for any-grade infections, 2.02% for severe infections, 1.74% for opportunistic infections, 1.56% for herpes zoster, and 0.49% for pneumonia in patients treated with any JAKi during the follow-up period. Treatment with specific JAKi in patients with RA is associated with an increased risk of any-grade and opportunistic infections but not severe infection. Close clinical monitoring of patients with RA treated with JAKi is required to establish the long-term infection risk profile of these agents.

Molecular Dynamics Simulations Help Determine the Molecular Mechanisms of Lasioglossin-III and Its Variant Peptides' Membrane Interfacial Interactions.

Lasioglossin-III (LL-III) is a potent broad-spectrum antimicrobial peptide used in diverse antimicrobial applications. In this work, coarse-grained and all-atom molecular dynamics simulation strategies were used in tandem to interpret the molecular mechanisms involved in the interfacial dynamics of LL-III and its recombinant variants during interactions with diverse cell membrane systems. Our results indicate that the membrane charges act as the driving force for initiating the membrane-peptide interactions, while the hydrophobic or van der Waals forces help to reinforce the membrane-peptide bindings. The optimized charge-hydrophobicity ratio of the LL-III peptides helps ensure their high specificity toward bacterial membranes compared to mammalian membrane systems, which also helps explain our experimental observations. Overall, we hope that our work gives new insight into the antimicrobial action of LL-III peptides and that the adopted simulation strategy will help other scientists and engineers extract maximal information from complex molecular simulations using minimal computational power.

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.

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.

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.

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.

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.

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.

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.