Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America最新文献

{"title":"Predictors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following High-Risk Exposure.","authors":"Kristin L Andrejko, Jake Pry, Jennifer F Myers, John Openshaw, James Watt, Nozomi Birkett, Jennifer L DeGuzman, Camilla M Barbaduomo, Zheng N Dong, Anna T Fang, Paulina M Frost, Timothy Ho, Mahsa H Javadi, Sophia S Li, Vivian H Tran, Christine Wan, Seema Jain, Joseph A Lewnard","doi":"10.1093/cid/ciab1040","DOIUrl":"10.1093/cid/ciab1040","url":null,"abstract":"<p><strong>Background: </strong>Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified.</p><p><strong>Methods: </strong>We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-12 November, 2021. We used conditional logistic regression to estimate adjusted odds ratios (aORs) of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 (\"high-risk exposure\") ≤14 days before testing.</p><p><strong>Results: </strong>751 of 1448 cases (52%) and 255 of 1443 controls (18%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 3.02-fold (95% confidence interval: 1.75-5.22) higher when high-risk exposures occurred with household members (vs. other contacts), 2.10-fold (1.05-4.21) higher when exposures occurred indoors (vs. outdoors only), and 2.15-fold (1.27-3.67) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Cases were less likely than controls to report mask usage during high-risk exposures (aOR = 0.50 [0.29-0.85]). The adjusted odds of case status was lower for fully-vaccinated (aOR = 0.25 [0.15-0.43]) participants compared to unvaccinated participants. Benefits of mask usage were greatest among unvaccinated and partially-vaccinated participants, and in interactions involving non-household contacts or interactions occurring without physical contact.</p><p><strong>Conclusions: </strong>NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e276-e288"},"PeriodicalIF":0.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study.","authors":"Paolo Denti, Roeland E Wasmann, Annelies van Rie, Jana Winckler, Adrie Bekker, Helena Rabie, Anneke C Hesseling, Louvina E van der Laan, Carmen Gonzalez-Martinez, Heather J Zar, Gerry Davies, Lubbe Wiesner, Elin M Svensson, Helen M McIlleron","doi":"10.1093/cid/ciab908","DOIUrl":"10.1093/cid/ciab908","url":null,"abstract":"<p><strong>Background: </strong>In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) tablet of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with revised weight bands.</p><p><strong>Methods: </strong>Children with drug-susceptible tuberculosis in Malawi and South Africa underwent pharmacokinetic sampling while receiving first-line tuberculosis drugs as single formulations according the 2010 WHO recommended doses. Nonlinear mixed-effects modeling and simulation was used to design the optimal FDC and weight-band dosing strategy for achieving the pharmacokinetic targets based on literature-derived adult AUC0-24h for rifampicin (38.7-72.9), isoniazid (11.6-26.3), and pyrazinamide (233-429 mg ∙ h/L).</p><p><strong>Results: </strong>In total, 180 children (42% female; 13.9% living with human immunodeficiency virus [HIV]; median [range] age 1.9 [0.22-12] years; weight 10.7 [3.20-28.8] kg) were administered 1, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) daily for 4-8, 8-12, 12-16, and 16-25 kg weight bands, respectively. Rifampicin exposure (for weight and age) was up to 50% lower than in adults. Increasing the tablet number resulted in adequate rifampicin but relatively high isoniazid and pyrazinamide exposures. Administering 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20. and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs.</p><p><strong>Conclusions: </strong>Current pediatric FDC doses resulted in low rifampicin exposures. Optimal dosing of all drugs cannot be achieved with the current FDCs. We propose a new FDC formulation and revised weight bands.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"141-151"},"PeriodicalIF":0.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402673/pdf/ciab908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39531121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Vulnerability and Rurality Associated With Higher Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Induced Seroprevalence: A Nationwide Blood Donor Study-United States, July 2020-June 2021.","authors":"Zheng Li,&nbsp;Brian Lewis,&nbsp;Kevin Berney,&nbsp;Elaine Hallisey,&nbsp;Austin M Williams,&nbsp;Ari Whiteman,&nbsp;Luis O Rivera-González,&nbsp;Kristie E N Clarke,&nbsp;Heather B Clayton,&nbsp;Terry Tincher,&nbsp;Jean D Opsomer,&nbsp;Michael P Busch,&nbsp;Adi V Gundlapalli,&nbsp;Jefferson M Jones","doi":"10.1093/cid/ciac105","DOIUrl":"https://doi.org/10.1093/cid/ciac105","url":null,"abstract":"<p><strong>Background: </strong>Most studies on health disparities during the coronavirus disease 2019 (COVID-19) pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence in the United States and its associations with race/ethnicity, rurality, and social vulnerability over time.</p><p><strong>Methods: </strong>This repeated cross-sectional study used data from blood donations in 50 states and Washington, DC, from July 2020 through June 2021. Donor zip codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its 4 themes were quantified using multivariate regression models.</p><p><strong>Results: </strong>Weighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or more socially vulnerable counties, after adjusting for demographic and geographic covariates.</p><p><strong>Conclusions: </strong>The findings demonstrated increasing SARS-CoV-2 seroprevalence in the United States across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e133-e143"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903418/pdf/ciac105.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Reported Deaths Among Fully Vaccinated Persons With Coronavirus Disease 2019-United States, January-April 2021.","authors":"Louise K François Watkins,&nbsp;Kiren Mitruka,&nbsp;Layne Dorough,&nbsp;Sara S Bressler,&nbsp;Kiersten J Kugeler,&nbsp;Katrin S Sadigh,&nbsp;Meseret G Birhane,&nbsp;Leisha D Nolen,&nbsp;Marc Fischer","doi":"10.1093/cid/ciac066","DOIUrl":"https://doi.org/10.1093/cid/ciac066","url":null,"abstract":"<p><strong>Background: </strong>Vaccines against coronavirus disease 2019 (COVID-19) are highly efficacious, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections do occur after vaccination. We characterized COVID-19 cases among fully vaccinated persons with an outcome of death.</p><p><strong>Methods: </strong>We analyzed COVID-19 cases voluntarily reported to the Centers for Disease Control and Prevention by US health departments from 1 January to 30 April 2021. We included cases among US residents with a positive SARS-CoV-2 test result ≥14 days after completion of an authorized primary vaccine series and who had a known outcome (alive or dead) as of 31 May 2021. When available, specimens were sequenced for viral lineage and death certificates were reviewed for cause(s) of death.</p><p><strong>Results: </strong>Of 8084 fully vaccinated persons with reported COVID-19 during the surveillance period, 245 (3.0%) died. Compared with patients who remained alive, those who died were older (median age, 82 vs 57 years;), more likely to reside in a long-term care facility (51% vs 18%), and more likely to have ≥1 underlying health condition associated with risk for severe disease (64% vs 24%) (all P < .01). Among 245 deaths, 191 (78%) were classified as COVID-19 related. Of 106 deaths with available death certificates, COVID-19 was listed for 81 deaths (77%). There were no differences in the type of vaccine administered or the most common viral lineage (B.1.1.7).</p><p><strong>Conclusions: </strong>COVID-19 deaths are rare in fully vaccinated persons, occurring most commonly in those with risk factors for severe disease, including older age and underlying health conditions. All eligible persons should be fully vaccinated against COVID-19 and follow other prevention measures to mitigate exposure risk.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e645-e652"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807315/pdf/ciac066.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39959311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi.","authors":"Louisa Pollock,&nbsp;Aisleen Bennett,&nbsp;Khuzwayo C Jere,&nbsp;Jonathan Mandolo,&nbsp;Queen Dube,&nbsp;Naor Bar-Zeev,&nbsp;Robert S Heyderman,&nbsp;Nigel A Cunliffe,&nbsp;Miren Iturriza-Gomara","doi":"10.1093/cid/ciab895","DOIUrl":"https://doi.org/10.1093/cid/ciab895","url":null,"abstract":"<p><strong>Background: </strong>Rotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. Although plasma rotavirus (RV)-specific immunoglobulin A (IgA) appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants.</p><p><strong>Methods: </strong>In a case-control study, we recruited infants presenting with severe rotavirus gastroenteritis following monovalent oral rotavirus vaccination (RV1 vaccine failures). Conditional logistic regression was used to determine the odds of rotavirus seronegativity (RV-specific IgA < 20 U/mL) in these cases compared 1:1 with age-matched, vaccinated, asymptomatic community controls. Plasma RV-specific IgA was determined by enzyme-linked immunosorbent assay for all participants at recruitment, and for cases at 10 days after symptom onset. Rotavirus infection and genotype were determined by antigen testing and reverse transcription-polymerase chain reaction, respectively.</p><p><strong>Results: </strong>In 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: odds ratio, 3.1 (95% confidence interval [CI], 1.6-5.9), P=.001. In 60 infants with convalescent serology, 42/45 (93%; 95% CI. 81-98) infants seronegative at baseline became seropositive. Median rise in RV-specific IgA concentration following acute infection was 112.8 (interquartile range, 19.1-380.6)-fold.</p><p><strong>Conclusions: </strong>In this vaccinated population with high residual burden of rotavirus disease, RV1 vaccine failure was associated with lower RV-specific IgA, providing further evidence of RV-specific IgA as a marker of protection. Robust convalescent RV-specific IgA response in vaccine failures suggests differences in wild-type and vaccine-induced immunity, which informs future vaccine development.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"41-46"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402641/pdf/ciab895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39632074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Positive Severe Acute Respiratory Syndrome Coronavirus Polymerase Chain Reaction After Coronavirus Disease 2019 Vaccination With up to 8 Months of Follow-up: Real-life Data From the Capital Region of Denmark.","authors":"Line Dam Heftdal,&nbsp;Martin Schultz,&nbsp;Theis Lange,&nbsp;Andreas Dehlbæk Knudsen,&nbsp;Kamille Fogh,&nbsp;Rasmus Bo Hasselbalch,&nbsp;Christine Borgen Linander,&nbsp;Thomas Kallemose,&nbsp;Henning Bundgaard,&nbsp;Kirsten Grønbæk,&nbsp;Palle Valentiner-Branth,&nbsp;Kasper Iversen,&nbsp;Susanne Dam Nielsen","doi":"10.1093/cid/ciac012","DOIUrl":"https://doi.org/10.1093/cid/ciac012","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19) vaccines are implemented worldwide in efforts to curb the pandemic. This study investigates the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT-PCR) test following BNT162b2 vaccination in a large real-life population in Denmark.</p><p><strong>Methods: </strong>Vaccination status and positive SARS-CoV-2 RT-PCR results from adults in the Capital Region of Denmark (n = 1 549 488) were obtained from national registries. PCR testing was free and widely available. The number of positive PCR tests per individual at risk was calculated as weekly rates. Time to positive PCR test was modelled using Kaplan-Meier methods and hazard ratios (HRs) were calculated using Cox regression.</p><p><strong>Results: </strong>A total of 1 119 574 individuals received the first dose of BNT162b2 and 1 088 879 received a second dose of BNT162b2. Individuals were followed up to 8.7 months after first dose (median: 5.5 months; interquartile ratio: 4.1-8.7). Rates of PCR-confirmed SARS-CoV-2 infection 2-4 months after the second dose were 0.21, 0.33, and 0.36 per 1000 individuals per week at risk for July, August, and September, respectively. Four or more months after the second dose, the rates were 0.56, 0.76, and 0.53 per 1000 individuals per week at risk for July, August, and September, respectively. HR of SARS-CoV-2 infection after the second dose was 0.2 (95% confidence interval, .05-.48; P = .001) for individuals with 8 months' follow-up.</p><p><strong>Conclusions: </strong>Individuals who received 2 doses of the BNT162b2 COVID-19 vaccine had a low risk of breakthrough infection after up to 8 months of follow-up. However, there was a tendency toward higher rates with longer follow-up.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e675-e682"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807191/pdf/ciac012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39812747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproduction Numbers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants: A Systematic Review and Meta-analysis.","authors":"Zhanwei Du,&nbsp;Caifen Liu,&nbsp;Chunyu Wang,&nbsp;Lingfeng Xu,&nbsp;Mingda Xu,&nbsp;Lin Wang,&nbsp;Yuan Bai,&nbsp;Xiaoke Xu,&nbsp;Eric H Y Lau,&nbsp;Peng Wu,&nbsp;Benjamin J Cowling","doi":"10.1093/cid/ciac137","DOIUrl":"https://doi.org/10.1093/cid/ciac137","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic continues to pose substantial risks to public health, worsened by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that may have a higher transmissibility and reduce vaccine effectiveness. We conducted a systematic review and meta-analysis on reproduction numbers of SARS-CoV-2 variants and provided pooled estimates for each variant.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e293-e295"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903374/pdf/ciac137.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39928799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.","authors":"Essy Mozaffari,&nbsp;Aastha Chandak,&nbsp;Zhiji Zhang,&nbsp;Shuting Liang,&nbsp;Mark Thrun,&nbsp;Robert L Gottlieb,&nbsp;Daniel R Kuritzkes,&nbsp;Paul E Sax,&nbsp;David A Wohl,&nbsp;Roman Casciano,&nbsp;Paul Hodgkins,&nbsp;Richard Haubrich","doi":"10.1093/cid/ciab875","DOIUrl":"https://doi.org/10.1093/cid/ciab875","url":null,"abstract":"<p><strong>Background: </strong>Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited.</p><p><strong>Methods: </strong>We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO.</p><p><strong>Results: </strong>A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days.</p><p><strong>Conclusions: </strong>RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e450-e458"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/35/ciab875.PMC9402660.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39478627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-year Efficacy and Safety of Takeda's Dengue Vaccine Candidate (TAK-003).","authors":"Luis Rivera,&nbsp;Shibadas Biswal,&nbsp;Xavier Sáez-Llorens,&nbsp;Humberto Reynales,&nbsp;Eduardo López-Medina,&nbsp;Charissa Borja-Tabora,&nbsp;Lulu Bravo,&nbsp;Chukiat Sirivichayakul,&nbsp;Pope Kosalaraksa,&nbsp;Luis Martinez Vargas,&nbsp;Delia Yu,&nbsp;Veerachai Watanaveeradej,&nbsp;Felix Espinoza,&nbsp;Reynaldo Dietze,&nbsp;LakKumar Fernando,&nbsp;Pujitha Wickramasinghe,&nbsp;Edson Duarte MoreiraJr,&nbsp;Asvini D Fernando,&nbsp;Dulanie Gunasekera,&nbsp;Kleber Luz,&nbsp;Rivaldo Venâncioda Cunha,&nbsp;Martina Rauscher,&nbsp;Olaf Zent,&nbsp;Mengya Liu,&nbsp;Elaine Hoffman,&nbsp;Inge LeFevre,&nbsp;Vianney Tricou,&nbsp;Derek Wallace,&nbsp;MariaTheresa Alera,&nbsp;Astrid Borkowski","doi":"10.1093/cid/ciab864","DOIUrl":"https://doi.org/10.1093/cid/ciab864","url":null,"abstract":"<p><strong>Background: </strong>Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data.</p><p><strong>Methods: </strong>Healthy 4-16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction.</p><p><strong>Results: </strong>Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6-66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8-88.4) against hospitalized VCD. Efficacy was 54.3% (41.9-64.1) against VCD and 77.1% (58.6-87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9-70.1) against VCD and 86.0% (78.4-91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5-54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6-83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified.</p><p><strong>Conclusions: </strong>TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"107-117"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/f7/ciab864.PMC9402653.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39486024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of Remdesivir in Adults Hospitalized With Coronavirus Disease 2019 (COVID-19): A Retrospective, Multicenter Comparative Effectiveness Study.","authors":"Brian T Garibaldi,&nbsp;Kunbo Wang,&nbsp;Matthew L Robinson,&nbsp;Joshua Betz,&nbsp;G Caleb Alexander,&nbsp;Kathleen M Andersen,&nbsp;Corey S Joseph,&nbsp;Hemalkumar B Mehta,&nbsp;Kimberly Korwek,&nbsp;Kenneth E Sands,&nbsp;Arielle M Fisher,&nbsp;Robert C Bollinger,&nbsp;Yanxun Xu","doi":"10.1093/cid/ciab1035","DOIUrl":"https://doi.org/10.1093/cid/ciab1035","url":null,"abstract":"<p><strong>Background: </strong>There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).</p><p><strong>Methods: </strong>This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death.</p><p><strong>Results: </strong>Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls).</p><p><strong>Conclusions: </strong>These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"e516-e524"},"PeriodicalIF":11.8,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754724/pdf/ciab1035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39728826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}