Pub Date : 2021-03-10DOI: 10.1101/2021.03.08.21252905
J. Hirschtick, Andrea R. Titus, Elizabeth Slocum, Laura E. Power, R. Hirschtick, M. Elliott, P. McKane, N. Fleischer
Importance: Emerging evidence suggests many people have persistent symptoms after acute COVID-19 illness. Objective: To estimate the prevalence and correlates of persistent COVID-19 symptoms 30 and 60 days post onset using a population-based sample. Design & Setting: The Michigan COVID-19 Recovery Surveillance Study is a population-based cross-sectional survey of a probability sample of adults with confirmed COVID-19 in the Michigan Disease Surveillance System (MDSS). Respondents completed a survey online or via telephone in English, Spanish, or Arabic between June - December 2020. Participants: Living non-institutionalized adults (aged 18+) in MDSS with COVID-19 onset through mid-April 2020 were eligible for selection (n=28,000). Among 2,000 adults selected, 629 completed the survey. We excluded 79 cases during data collection due to ineligibility, 6 asymptomatic cases, 7 proxy reports, and 24 cases missing outcome data, resulting in a sample size of 593. The sample was predominantly female (56.1%), aged 45 and older (68.2%), and Non-Hispanic White (46.3%) or Black (34.8%). Exposures: Demographic (age, sex, race/ethnicity, and annual household income) and clinical factors (smoking status, body mass index, diagnosed comorbidities, and illness severity). Main outcomes and Measures: We defined post-acute sequelae of SARS-CoV-2 infection (PASC) as persistent symptoms 30+ days (30-day COVID-19) or 60+ days (60-day COVID-19) post COVID-19 onset. Results: 30- and 60-day COVID-19 were highly prevalent (52.5% and 35.0%), even among respondents reporting mild symptoms (29.2% and 24.5%) and non-hospitalized respondents (43.7% and 26.9%, respectively). Low income was statistically significantly associated with 30-day COVID-19 in adjusted models. Respondents reporting very severe (vs. mild) symptoms had 2.25 times higher prevalence of 30-day COVID-19 (Adjusted Prevalence Ratio [aPR] 2.25, 95% CI 1.46-3.46) and 1.71 times higher prevalence of 60-day COVID-19 (aPR 1.71, 95% 1.02-2.88). Hospitalized (vs. non-hospitalized) respondents had about 40% higher prevalence of both 30-day (aPR 1.37, 95% CI 1.12-1.69) and 60-day COVID-19 (aPR 1.40, 95% CI 1.02-1.93). Conclusions and Relevance: PASC is highly prevalent among cases with severe initial symptoms, and, to a lesser extent, cases with mild and moderate symptoms.
重要性:新出现的证据表明,许多人在急性COVID-19疾病后会出现持续症状。目的:通过基于人群的样本估计发病后30天和60天持续COVID-19症状的患病率及其相关因素。设计与环境:密歇根州COVID-19康复监测研究是一项基于人群的横断面调查,调查对象是密歇根州疾病监测系统(MDSS)中确诊COVID-19的成人概率样本。受访者在2020年6月至12月期间以英语、西班牙语或阿拉伯语在线或通过电话完成了调查。参与者:截至2020年4月中旬,MDSS中患有COVID-19发病的生活非机构成年人(18岁以上)符合入选条件(n=28,000)。在2000名被选中的成年人中,629人完成了调查。我们在数据收集过程中排除了79例不合格病例、6例无症状病例、7例代理报告和24例缺少结局数据,样本量为593例。样本主要为女性(56.1%),45岁及以上(68.2%),非西班牙裔白人(46.3%)或黑人(34.8%)。暴露:人口统计学因素(年龄、性别、种族/民族和家庭年收入)和临床因素(吸烟状况、体重指数、诊断出的合并症和疾病严重程度)。主要结局和指标:我们将SARS-CoV-2感染急性后后遗症(PASC)定义为COVID-19发病后30天以上(30天)或60天以上(60天)的持续症状。结果:30天和60天的COVID-19非常普遍(52.5%和35.0%),即使在报告轻微症状的受访者(29.2%和24.5%)和未住院的受访者(分别为43.7%和26.9%)中也是如此。在调整后的模型中,低收入与30天COVID-19有统计学显著相关。报告非常严重(与轻度)症状的受访者30天COVID-19患病率高2.25倍(调整患病率比[aPR] 2.25, 95% CI 1.46-3.46), 60天COVID-19患病率高1.71倍(aPR 1.71, 95% 1.02-2.88)。住院(与非住院)的受访者在30天(aPR 1.37, 95% CI 1.12-1.69)和60天(aPR 1.40, 95% CI 1.02-1.93)的COVID-19患病率均高出约40%。结论和相关性:PASC在初始症状严重的病例中非常普遍,在轻度和中度症状的病例中患病率较低。
{"title":"Population-based estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) prevalence and characteristics","authors":"J. Hirschtick, Andrea R. Titus, Elizabeth Slocum, Laura E. Power, R. Hirschtick, M. Elliott, P. McKane, N. Fleischer","doi":"10.1101/2021.03.08.21252905","DOIUrl":"https://doi.org/10.1101/2021.03.08.21252905","url":null,"abstract":"Importance: Emerging evidence suggests many people have persistent symptoms after acute COVID-19 illness. Objective: To estimate the prevalence and correlates of persistent COVID-19 symptoms 30 and 60 days post onset using a population-based sample. Design & Setting: The Michigan COVID-19 Recovery Surveillance Study is a population-based cross-sectional survey of a probability sample of adults with confirmed COVID-19 in the Michigan Disease Surveillance System (MDSS). Respondents completed a survey online or via telephone in English, Spanish, or Arabic between June - December 2020. Participants: Living non-institutionalized adults (aged 18+) in MDSS with COVID-19 onset through mid-April 2020 were eligible for selection (n=28,000). Among 2,000 adults selected, 629 completed the survey. We excluded 79 cases during data collection due to ineligibility, 6 asymptomatic cases, 7 proxy reports, and 24 cases missing outcome data, resulting in a sample size of 593. The sample was predominantly female (56.1%), aged 45 and older (68.2%), and Non-Hispanic White (46.3%) or Black (34.8%). Exposures: Demographic (age, sex, race/ethnicity, and annual household income) and clinical factors (smoking status, body mass index, diagnosed comorbidities, and illness severity). Main outcomes and Measures: We defined post-acute sequelae of SARS-CoV-2 infection (PASC) as persistent symptoms 30+ days (30-day COVID-19) or 60+ days (60-day COVID-19) post COVID-19 onset. Results: 30- and 60-day COVID-19 were highly prevalent (52.5% and 35.0%), even among respondents reporting mild symptoms (29.2% and 24.5%) and non-hospitalized respondents (43.7% and 26.9%, respectively). Low income was statistically significantly associated with 30-day COVID-19 in adjusted models. Respondents reporting very severe (vs. mild) symptoms had 2.25 times higher prevalence of 30-day COVID-19 (Adjusted Prevalence Ratio [aPR] 2.25, 95% CI 1.46-3.46) and 1.71 times higher prevalence of 60-day COVID-19 (aPR 1.71, 95% 1.02-2.88). Hospitalized (vs. non-hospitalized) respondents had about 40% higher prevalence of both 30-day (aPR 1.37, 95% CI 1.12-1.69) and 60-day COVID-19 (aPR 1.40, 95% CI 1.02-1.93). Conclusions and Relevance: PASC is highly prevalent among cases with severe initial symptoms, and, to a lesser extent, cases with mild and moderate symptoms.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73971239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-03DOI: 10.1101/2021.03.02.21252750
M. Choudhary, Charles R. Crain, Xueting Qiu, W. Hanage, Jonathan Z. Li
Background. Both SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods. A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 to community-driven evolution. Results. Fourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 and N genes. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment. Conclusions. SARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.
{"title":"SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection","authors":"M. Choudhary, Charles R. Crain, Xueting Qiu, W. Hanage, Jonathan Z. Li","doi":"10.1101/2021.03.02.21252750","DOIUrl":"https://doi.org/10.1101/2021.03.02.21252750","url":null,"abstract":"Background. Both SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods. A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 to community-driven evolution. Results. Fourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 and N genes. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment. Conclusions. SARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84898090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1101/2021.01.29.21250317
A. Karaba, Weiqiang Zhou, L. Hsieh, Alexis Figueroa, G. Massaccesi, R. Rothman, K. Fenstermacher, L. Sauer, Kathryn Shaw-Saliba, P. Blair, S. Leung, R. Wesson, N. Alachkar, R. El-Diwany, Hongkai Ji, A. Cox
Background: Several inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. Methods: Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity. Results: IL-18, IL-1{beta}, IL-6, and TNF- were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-{gamma}, IFN-{lambda}1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF- were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-{lambda}1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. Conclusions: These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.
{"title":"Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology","authors":"A. Karaba, Weiqiang Zhou, L. Hsieh, Alexis Figueroa, G. Massaccesi, R. Rothman, K. Fenstermacher, L. Sauer, Kathryn Shaw-Saliba, P. Blair, S. Leung, R. Wesson, N. Alachkar, R. El-Diwany, Hongkai Ji, A. Cox","doi":"10.1101/2021.01.29.21250317","DOIUrl":"https://doi.org/10.1101/2021.01.29.21250317","url":null,"abstract":"Background: Several inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. Methods: Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity. Results: IL-18, IL-1{beta}, IL-6, and TNF- were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-{gamma}, IFN-{lambda}1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF- were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-{lambda}1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. Conclusions: These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"20 1","pages":"254 - 262"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87017312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-07DOI: 10.1101/2021.01.06.21249345
S. Dalai, J. N. Dines, T. Snyder, R. Gittelman, Tera Eerkes, Pashmi Vaney, S. Howard, K. Akers, L. Skewis, Anthony Monteforte, P. Witte, C. Wolf, Hans P. Nesse, M. Herndon, Jia Qadeer, Sarah Duffy, E. Svejnoha, Caroline Taromino, I. Kaplan, J. Alsobrook, T. Manley, L. Baldo
Background While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed and scale, critical gaps remain in our understanding of the immune response to SARS-CoV-2. Current diagnostic strategies, including serology, have numerous limitations in addressing these gaps. Here we describe clinical performance of T-Detect COVID, the first reported assay to determine recent or prior SARS-CoV-2 infection based on T-cell receptor (TCR) sequencing and immune repertoire profiling from whole blood samples. Methods Methods for high-throughput immunosequencing of the TCR{beta} gene from blood specimens have been described1. We developed a statistical classifier showing high specificity for identifying prior SARS-CoV-2 infection2, utilizing >4,000 SARS-CoV-2-associated TCR sequences from 784 cases and 2,447 controls across 5 independent cohorts. The T-Detect COVID Assay comprises immunosequencing and classifier application to yield a qualitative positive or negative result. Several retrospective and prospective cohorts were enrolled to assess assay performance including primary and secondary Positive Percent Agreement (PPA; N=205, N=77); primary and secondary Negative Percent Agreement (NPA; N=87, N=79); PPA compared to serology (N=55); and pathogen cross-reactivity (N=38). Results T-Detect COVID demonstrated high PPA in subjects with prior PCR-confirmed SARS-CoV-2 infection (97.1% 15+ days from diagnosis; 94.5% 15+ days from symptom onset), high NPA (~100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than two commercial EUA serology tests, and no evidence of pathogen cross-reactivity. Conclusion T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance to identify recent or prior SARS-CoV-2 infection from standard blood samples. This assay can provide critical insights on the SARS-CoV-2 immune response, with potential implications for clinical management, risk stratification, surveillance, assessing protective immunity, and understanding long-term sequelae.
虽然COVID-19大流行的诊断、治疗和疫苗开发以前所未有的速度和规模进行,但我们对SARS-CoV-2免疫反应的理解仍然存在重大差距。目前的诊断策略,包括血清学,在解决这些差距方面存在许多局限性。本文描述了T-Detect COVID的临床表现,这是首次报道的基于t细胞受体(TCR)测序和全血样本免疫库分析来确定近期或既往SARS-CoV-2感染的检测方法。方法描述了血液标本中TCR{β}基因的高通量免疫测序方法。我们开发了一个统计分类器,显示出高度特异性,用于识别先前的SARS-CoV-2感染2,利用来自5个独立队列的784例病例和2447例对照的超过4000个SARS-CoV-2相关TCR序列。T-Detect COVID Assay包括免疫测序和分类器应用,以产生定性阳性或阴性结果。几个回顾性和前瞻性队列被纳入评估分析性能,包括主要和次要阳性百分比协议(PPA;N = 205, N = 77);主要和次要负百分比协议(NPA);N = 87, N = 79);PPA与血清学比较(N=55);病原体交叉反应性(N=38)。结果T-Detect COVID在既往pcr确诊的SARS-CoV-2感染的受试者中显示高PPA(97.1%),在诊断后15天以上;在推定或确诊的SARS-CoV-2阴性病例中,NPA高(~100%),PPA等于或高于两次商业EUA血清学检测,并且没有证据表明病原体存在交叉反应性。结论T-Detect COVID是一种新型的t细胞免疫测序检测方法,具有很高的临床性能,可以从标准血液样本中识别近期或既往的SARS-CoV-2感染。该检测可以为SARS-CoV-2免疫反应提供重要见解,对临床管理、风险分层、监测、评估保护性免疫和了解长期后遗症具有潜在意义。
{"title":"Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection","authors":"S. Dalai, J. N. Dines, T. Snyder, R. Gittelman, Tera Eerkes, Pashmi Vaney, S. Howard, K. Akers, L. Skewis, Anthony Monteforte, P. Witte, C. Wolf, Hans P. Nesse, M. Herndon, Jia Qadeer, Sarah Duffy, E. Svejnoha, Caroline Taromino, I. Kaplan, J. Alsobrook, T. Manley, L. Baldo","doi":"10.1101/2021.01.06.21249345","DOIUrl":"https://doi.org/10.1101/2021.01.06.21249345","url":null,"abstract":"Background While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed and scale, critical gaps remain in our understanding of the immune response to SARS-CoV-2. Current diagnostic strategies, including serology, have numerous limitations in addressing these gaps. Here we describe clinical performance of T-Detect COVID, the first reported assay to determine recent or prior SARS-CoV-2 infection based on T-cell receptor (TCR) sequencing and immune repertoire profiling from whole blood samples. Methods Methods for high-throughput immunosequencing of the TCR{beta} gene from blood specimens have been described1. We developed a statistical classifier showing high specificity for identifying prior SARS-CoV-2 infection2, utilizing >4,000 SARS-CoV-2-associated TCR sequences from 784 cases and 2,447 controls across 5 independent cohorts. The T-Detect COVID Assay comprises immunosequencing and classifier application to yield a qualitative positive or negative result. Several retrospective and prospective cohorts were enrolled to assess assay performance including primary and secondary Positive Percent Agreement (PPA; N=205, N=77); primary and secondary Negative Percent Agreement (NPA; N=87, N=79); PPA compared to serology (N=55); and pathogen cross-reactivity (N=38). Results T-Detect COVID demonstrated high PPA in subjects with prior PCR-confirmed SARS-CoV-2 infection (97.1% 15+ days from diagnosis; 94.5% 15+ days from symptom onset), high NPA (~100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than two commercial EUA serology tests, and no evidence of pathogen cross-reactivity. Conclusion T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance to identify recent or prior SARS-CoV-2 infection from standard blood samples. This assay can provide critical insights on the SARS-CoV-2 immune response, with potential implications for clinical management, risk stratification, surveillance, assessing protective immunity, and understanding long-term sequelae.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78563219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-23DOI: 10.1101/2020.11.20.20235697
L. Grandjean, Anja Saso, A. Ortiz, Tanya Lam, J. Hatcher, Rosie Thistlethwayte, M. Harris, T. Best, Marina Johnson, H. Wagstaffe, E. Ralph, Annabelle Mai, C. Colijn, J. Breuer, M. Buckland, K. Gilmour, D. Goldblatt
Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virus in-vitro. Similarly, animal challenge models suggest that neutralizing antibodies isolated from SARS-CoV-2 infected individuals prevent against disease upon re-exposure to the virus. Understanding the nature and duration of the antibody response following SARS-CoV-2 infection is therefore critically important. Methods: Between April and October 2020 we undertook a prospective cohort study of 3555 healthcare workers in order to elucidate the duration and dynamics of antibody responses following infection with SARS-CoV-2. After a formal performance evaluation against 169 PCR confirmed cases and negative controls, the Meso-Scale Discovery assay was used to quantify in parallel, antibody titers to the SARS-CoV-2 nucleoprotein (N), spike (S) protein and the receptor-binding-domain (RBD) of the S-protein. All seropositive participants were followed up monthly for a maximum of 7 months; those participants that were symptomatic, with known dates of symptom-onset, seropositive by the MSD assay and who provided 2 or more monthly samples were included in the analysis. Survival analysis was used to determine the proportion of sero-reversion (switching from positive to negative) from the raw data. In order to predict long-term antibody dynamics, two hierarchical longitudinal Gamma models were implemented to provide predictions for the lower bound (continuous antibody decay to zero, 'Gamma-decay') and upper bound (decay-to-plateau due to long lived plasma cells, 'Gamma-plateau') long-term antibody titers. Results: A total of 1163 samples were provided from 349 of 3555 recruited participants who were symptomatic, seropositive by the MSD assay, and were followed up with 2 or more monthly samples. At 200 days post symptom onset, 99% of participants had detectable S-antibody whereas only 75% of participants had detectable N-antibody. Even under our most pessimistic assumption of persistent negative exponential decay, the S-antibody was predicted to remain detectable in 95% of participants until 465 days [95% CI 370-575] after symptom onset. Under the Gamma-plateau model, the entire posterior distribution of S-antibody titers at plateau remained above the threshold for detection indefinitely. Surrogate neutralization assays demonstrated a strong positive correlation between antibody titers to the S-protein and blocking of the ACE-2 receptor in-vitro [R2=0.72, p<0.001]. By contrast, the N-antibody waned rapidly with a half-life of 60 days [95% CI 52-68]. Discussion: This study has demonstrated persistence of the spike antibody in 99% of participants at 200 days following SARS-CoV-2 symptoms and rapid decay of the nucleoprotein antibody. Diagnostic tests or studies that rely on the N-antibody as a measure of seroprevalence must be interpreted with caution. Our lowest bound prediction for duration of the spike antibody was 465 days and our upp
背景:严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)抗体已被证明能在体外中和该病毒。同样,动物攻击模型表明,从SARS-CoV-2感染个体中分离的中和抗体在再次接触该病毒时可以预防疾病。因此,了解SARS-CoV-2感染后抗体反应的性质和持续时间至关重要。方法:在2020年4月至10月期间,我们对3555名医护人员进行了前瞻性队列研究,以阐明感染SARS-CoV-2后抗体反应的持续时间和动态。在对169例PCR确诊病例和阴性对照进行正式性能评估后,使用Meso-Scale Discovery法平行定量SARS-CoV-2核蛋白(N)、刺突(S)蛋白和S蛋白的受体结合域(RBD)的抗体滴度。所有血清阳性的参与者每月随访最多7个月;那些有症状、已知症状出现日期、经MSD检测血清呈阳性、每月提供2次或更多样本的参与者被纳入分析。生存分析用于确定原始数据中血清逆转(从阳性转为阴性)的比例。为了预测长期抗体动态,实施了两个分层纵向Gamma模型,以提供下限(连续抗体衰减到零,“Gamma衰减”)和上限(由于长寿命浆细胞衰减到平台,“Gamma平台”)长期抗体滴度的预测。结果:招募的3555名参与者中有349名有症状,MSD检测呈血清阳性,共提供了1163份样本,并随访了2个月或更长时间的样本。在症状出现后200天,99%的参与者检测到s抗体,而只有75%的参与者检测到n抗体。即使在我们最悲观的持续负指数衰减假设下,预计95%的参与者在症状出现后465天内仍可检测到s抗体[95% CI 370-575]。在gamma -平台模型下,s抗体滴度在平台上的整个后验分布无限期地保持在检测阈值之上。替代中和试验表明,s蛋白抗体滴度与体外阻断ACE-2受体之间存在很强的正相关[R2=0.72, p<0.001]。相比之下,n抗体迅速消退,半衰期为60天[95% CI 52-68]。讨论:这项研究表明,在SARS-CoV-2症状出现200天后,99%的参与者体内的刺突抗体持续存在,核蛋白抗体迅速衰减。诊断测试或研究依赖于n抗体作为血清流行率的测量必须谨慎解释。我们对刺突抗体持续时间的下限预测为465天,我们的上限预测刺突抗体无限期地保持与报告的SARS-CoV感染的长期血清阳性一致。s抗体的长期存在,以及s抗体与体外病毒替代物中和之间的强正相关,对SARS-CoV-2感染后功能性免疫的持续时间具有重要意义。
{"title":"Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2","authors":"L. Grandjean, Anja Saso, A. Ortiz, Tanya Lam, J. Hatcher, Rosie Thistlethwayte, M. Harris, T. Best, Marina Johnson, H. Wagstaffe, E. Ralph, Annabelle Mai, C. Colijn, J. Breuer, M. Buckland, K. Gilmour, D. Goldblatt","doi":"10.1101/2020.11.20.20235697","DOIUrl":"https://doi.org/10.1101/2020.11.20.20235697","url":null,"abstract":"Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virus in-vitro. Similarly, animal challenge models suggest that neutralizing antibodies isolated from SARS-CoV-2 infected individuals prevent against disease upon re-exposure to the virus. Understanding the nature and duration of the antibody response following SARS-CoV-2 infection is therefore critically important. Methods: Between April and October 2020 we undertook a prospective cohort study of 3555 healthcare workers in order to elucidate the duration and dynamics of antibody responses following infection with SARS-CoV-2. After a formal performance evaluation against 169 PCR confirmed cases and negative controls, the Meso-Scale Discovery assay was used to quantify in parallel, antibody titers to the SARS-CoV-2 nucleoprotein (N), spike (S) protein and the receptor-binding-domain (RBD) of the S-protein. All seropositive participants were followed up monthly for a maximum of 7 months; those participants that were symptomatic, with known dates of symptom-onset, seropositive by the MSD assay and who provided 2 or more monthly samples were included in the analysis. Survival analysis was used to determine the proportion of sero-reversion (switching from positive to negative) from the raw data. In order to predict long-term antibody dynamics, two hierarchical longitudinal Gamma models were implemented to provide predictions for the lower bound (continuous antibody decay to zero, 'Gamma-decay') and upper bound (decay-to-plateau due to long lived plasma cells, 'Gamma-plateau') long-term antibody titers. Results: A total of 1163 samples were provided from 349 of 3555 recruited participants who were symptomatic, seropositive by the MSD assay, and were followed up with 2 or more monthly samples. At 200 days post symptom onset, 99% of participants had detectable S-antibody whereas only 75% of participants had detectable N-antibody. Even under our most pessimistic assumption of persistent negative exponential decay, the S-antibody was predicted to remain detectable in 95% of participants until 465 days [95% CI 370-575] after symptom onset. Under the Gamma-plateau model, the entire posterior distribution of S-antibody titers at plateau remained above the threshold for detection indefinitely. Surrogate neutralization assays demonstrated a strong positive correlation between antibody titers to the S-protein and blocking of the ACE-2 receptor in-vitro [R2=0.72, p<0.001]. By contrast, the N-antibody waned rapidly with a half-life of 60 days [95% CI 52-68]. Discussion: This study has demonstrated persistence of the spike antibody in 99% of participants at 200 days following SARS-CoV-2 symptoms and rapid decay of the nucleoprotein antibody. Diagnostic tests or studies that rely on the N-antibody as a measure of seroprevalence must be interpreted with caution. Our lowest bound prediction for duration of the spike antibody was 465 days and our upp","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"90 8 1","pages":"1220 - 1229"},"PeriodicalIF":0.0,"publicationDate":"2020-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88374112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz
BACKGROUND Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM). METHODS We analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression. RESULTS Among 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs. CONCLUSIONS Recent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.
{"title":"Chlamydia and Gonorrhea Incidence and Testing among Patients in the HIV Outpatient Study, 2007-2017.","authors":"Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz","doi":"10.1093/cid/ciz1085","DOIUrl":"https://doi.org/10.1093/cid/ciz1085","url":null,"abstract":"BACKGROUND\u0000Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM).\u0000\u0000\u0000METHODS\u0000We analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression.\u0000\u0000\u0000RESULTS\u0000Among 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs.\u0000\u0000\u0000CONCLUSIONS\u0000Recent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79212743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn
BACKGROUND Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects. METHODS Parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs). RESULTS By age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia. CONCLUSION BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.
{"title":"Early vaccination with BCG-Denmark or BCG-Japan versus BCG-Russia to healthy newborns in Guinea-Bissau: A randomized controlled trial.","authors":"F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn","doi":"10.1093/cid/ciz1080","DOIUrl":"https://doi.org/10.1093/cid/ciz1080","url":null,"abstract":"BACKGROUND\u0000Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects.\u0000\u0000\u0000METHODS\u0000Parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs).\u0000\u0000\u0000RESULTS\u0000By age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia.\u0000\u0000\u0000CONCLUSION\u0000BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"281 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91434831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten
BACKGROUND In the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage. METHODS In a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as "incidental", "short-term", "long-term" carrier or as "non-carrier". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data. RESULTS Out of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were "incidental carriers", 22 (3.3%) "short-term carriers", 38 (5.8%) "long-term carriers" and 530 (80.8%) "non-carrier". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero. CONCLUSION Risk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.
{"title":"Dynamics of intestinal carriage of Extended-spectrum Beta-lactamase producing Enterobacteriaceae in the Dutch general population (2014-2016).","authors":"G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten","doi":"10.1093/cid/ciz1091","DOIUrl":"https://doi.org/10.1093/cid/ciz1091","url":null,"abstract":"BACKGROUND\u0000In the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage.\u0000\u0000\u0000METHODS\u0000In a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as \"incidental\", \"short-term\", \"long-term\" carrier or as \"non-carrier\". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data.\u0000\u0000\u0000RESULTS\u0000Out of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were \"incidental carriers\", 22 (3.3%) \"short-term carriers\", 38 (5.8%) \"long-term carriers\" and 530 (80.8%) \"non-carrier\". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero.\u0000\u0000\u0000CONCLUSION\u0000Risk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77989690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott
BACKGROUND Approximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals. METHODS A transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens. RESULTS Across both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals. CONCLUSIONS Statistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.
{"title":"Impact of a Novel Antimicrobial Surface Coating on Healthcare-Associated Infections and Environmental Bioburden at Two Urban Hospitals.","authors":"K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott","doi":"10.1093/cid/ciz1077","DOIUrl":"https://doi.org/10.1093/cid/ciz1077","url":null,"abstract":"BACKGROUND\u0000Approximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals.\u0000\u0000\u0000METHODS\u0000A transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens.\u0000\u0000\u0000RESULTS\u0000Across both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals.\u0000\u0000\u0000CONCLUSIONS\u0000Statistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"124 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78383697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How much impact do antimicrobial surfaces really have on healthcare-acquired infection?","authors":"S. Dancer","doi":"10.1093/cid/ciz1078","DOIUrl":"https://doi.org/10.1093/cid/ciz1078","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"141 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86258484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}