Pub Date : 2021-06-22DOI: 10.1101/2021.06.22.448967
S. Argimón, S. David, A. Underwood, M. Abrudan, N. Wheeler, M. Kekre, Khalil AbuDahab, C. Yeats, Richard J. Goater, Ben Taylor, Harry Harste, Dawn Muddyman, E. Feil, S. Brisse, K. Holt, P. Donado-Godoy, K. Ravikumar, I. Okeke, C. Carlos, D. Aanensen
Background Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. Methods We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16,537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1,636 genomes from four low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Results Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (e.g. ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that three O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Conclusions Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance. 40-word summary Pathogenwatch is a free web-application for analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We improved the representation of genomes from middle-income countries through the Global Health Research Unit on AMR, further facilitating ongoing surveillance. FUNDING This work was supported by Official Development Assistance (ODA) funding from the National Institute of Health Research [grant number 16_136_111]. This research was commissioned by the National Institute of Health Research using Official Development Assistance (ODA) funding. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. CONFLICT OF INTEREST The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
{"title":"Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch","authors":"S. Argimón, S. David, A. Underwood, M. Abrudan, N. Wheeler, M. Kekre, Khalil AbuDahab, C. Yeats, Richard J. Goater, Ben Taylor, Harry Harste, Dawn Muddyman, E. Feil, S. Brisse, K. Holt, P. Donado-Godoy, K. Ravikumar, I. Okeke, C. Carlos, D. Aanensen","doi":"10.1101/2021.06.22.448967","DOIUrl":"https://doi.org/10.1101/2021.06.22.448967","url":null,"abstract":"Background Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. Methods We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16,537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1,636 genomes from four low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Results Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (e.g. ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that three O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Conclusions Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance. 40-word summary Pathogenwatch is a free web-application for analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We improved the representation of genomes from middle-income countries through the Global Health Research Unit on AMR, further facilitating ongoing surveillance. FUNDING This work was supported by Official Development Assistance (ODA) funding from the National Institute of Health Research [grant number 16_136_111]. This research was commissioned by the National Institute of Health Research using Official Development Assistance (ODA) funding. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. CONFLICT OF INTEREST The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"63 1","pages":"S325 - S335"},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74094463","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 : 2021-06-18DOI: 10.1101/2021.06.14.21258910
Lakshmi Chauhan, J. Pattee, Joshay A. Ford, C. Thomas, Kelsey E Lesteberg, Eric Richards, Carl A Bernas, M. Loi, Larry J. Dumont, K. Annen, M. Berg, Mercedes Zirbes, Vijaya Knight, A. Miller, T. Jenkins, T. Bennett, D. Monkowski, R. Boxer, J. D. Beckham
Background: The SARS-CoV2 pandemic has caused high inpatient mortality and morbidity throughout the world. COVID19 convalescent plasma has been utilized as a potential therapy for patients hospitalized with COVID19 pneumonia. This study evaluated the outcomes of hospitalized COVID19 patients treated with COVID19 convalescent plasma in a prospective, observational multicenter trial. Methods: From April 2020 through August 2020, hospitalized COVID19 patients at 16 participating hospitals in Colorado were enrolled and treated with COVID19 convalescent plasma (CCP) and compared to hospitalized patients with COVID19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated COVID19 hospitalized patients were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. Results: 542 total hospitalized COVID19 patients were enrolled at 16 hospitals across the region. A total of 468 hospitalized COVID19 patients were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared to controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. Conclusions: These data show that treatment of hospitalized COVID19 patients with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.
{"title":"A Multi-center, Prospective, Observational-cohort controlled study of Clinical Outcomes following COVID-19 Convalescent plasma therapy in hospitalized COVID-19 patients","authors":"Lakshmi Chauhan, J. Pattee, Joshay A. Ford, C. Thomas, Kelsey E Lesteberg, Eric Richards, Carl A Bernas, M. Loi, Larry J. Dumont, K. Annen, M. Berg, Mercedes Zirbes, Vijaya Knight, A. Miller, T. Jenkins, T. Bennett, D. Monkowski, R. Boxer, J. D. Beckham","doi":"10.1101/2021.06.14.21258910","DOIUrl":"https://doi.org/10.1101/2021.06.14.21258910","url":null,"abstract":"Background: The SARS-CoV2 pandemic has caused high inpatient mortality and morbidity throughout the world. COVID19 convalescent plasma has been utilized as a potential therapy for patients hospitalized with COVID19 pneumonia. This study evaluated the outcomes of hospitalized COVID19 patients treated with COVID19 convalescent plasma in a prospective, observational multicenter trial. Methods: From April 2020 through August 2020, hospitalized COVID19 patients at 16 participating hospitals in Colorado were enrolled and treated with COVID19 convalescent plasma (CCP) and compared to hospitalized patients with COVID19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated COVID19 hospitalized patients were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. Results: 542 total hospitalized COVID19 patients were enrolled at 16 hospitals across the region. A total of 468 hospitalized COVID19 patients were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared to controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. Conclusions: These data show that treatment of hospitalized COVID19 patients with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"39 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80906106","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 : 2021-05-20DOI: 10.21203/RS.3.RS-542072/V1
Bingyi Yang, T. Tsang, Huizhi Gao, E. Lau, Yun Lin, F. Ho, J. Xiao, J. Wong, D. Adam, Q. Liao, P. Wu, B. Cowling, G. Leung
BACKGROUND Testing of an entire community has been used as an approach to control COVID-19. In Hong Kong, a universal community testing programme (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognised infections, and analysed data from the UCTP and other sources to characterise transmission dynamics. METHODS We described the characteristics of people participating in the UCTP and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS. RESULTS 1.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100,000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% versus 27%, p <0.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave. CONCLUSIONS We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognised infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.
{"title":"Universal community nucleic acid testing for COVID-19 in Hong Kong reveals insights into transmission dynamics: a cross-sectional and modelling study.","authors":"Bingyi Yang, T. Tsang, Huizhi Gao, E. Lau, Yun Lin, F. Ho, J. Xiao, J. Wong, D. Adam, Q. Liao, P. Wu, B. Cowling, G. Leung","doi":"10.21203/RS.3.RS-542072/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-542072/V1","url":null,"abstract":"BACKGROUND\u0000Testing of an entire community has been used as an approach to control COVID-19. In Hong Kong, a universal community testing programme (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognised infections, and analysed data from the UCTP and other sources to characterise transmission dynamics.\u0000\u0000\u0000METHODS\u0000We described the characteristics of people participating in the UCTP and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS.\u0000\u0000\u0000RESULTS\u00001.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100,000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% versus 27%, p <0.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave.\u0000\u0000\u0000CONCLUSIONS\u0000We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognised infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.","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":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88649798","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 : 2021-04-09DOI: 10.1101/2021.04.05.21254834
M. Shah, P. Salvatore, L. Ford, Emiko Kamitani, M. Whaley, Mitchell Kaitlin, D. Currie, Clint N. Morgan, H. Segaloff, Shirley Lecher, Tarah Somers, Miriam E. Van Dyke, J. Bigouette, Augustina Delaney, Juliana DaSilva, M. O’Hegarty, L. Boyle-Estheimer, Fatima Abdirizak, Sandor E. Karpathy, J. Meece, L J Ivanić, K. Goffard, D. Gieryn, Alana Sterkel, A. Bateman, J. Kahrs, K. Langolf, T. Zochert, N. Knight, Christopher H. Hsu, H. Kirking, J. Tate
Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Same day antigen testing did not significantly improve test sensitivity while specificity remained high.
{"title":"Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020","authors":"M. Shah, P. Salvatore, L. Ford, Emiko Kamitani, M. Whaley, Mitchell Kaitlin, D. Currie, Clint N. Morgan, H. Segaloff, Shirley Lecher, Tarah Somers, Miriam E. Van Dyke, J. Bigouette, Augustina Delaney, Juliana DaSilva, M. O’Hegarty, L. Boyle-Estheimer, Fatima Abdirizak, Sandor E. Karpathy, J. Meece, L J Ivanić, K. Goffard, D. Gieryn, Alana Sterkel, A. Bateman, J. Kahrs, K. Langolf, T. Zochert, N. Knight, Christopher H. Hsu, H. Kirking, J. Tate","doi":"10.1101/2021.04.05.21254834","DOIUrl":"https://doi.org/10.1101/2021.04.05.21254834","url":null,"abstract":"Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Same day antigen testing did not significantly improve test sensitivity while specificity remained high.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82463675","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 : 2021-04-05DOI: 10.1101/2021.03.31.21254502
S. Buchan, S. Tibebu, N. Daneman, M. Whelan, T. Vanniyasingam, M. Murti, K. Brown
IMPORTANCE: Higher secondary attack rates related to variant of concern (VOC) index cases have been reported, but have not been explored within households, which continue to be an important source of coronavirus disease 2019 (COVID-19) transmission OBJECTIVE: To compare secondary attack rates in households with VOC versus non-VOC index cases. DESIGN: A retrospective cohort study of household index cases reported from February 7-27, 2021. A propensity-score matched cohort was derived to calculate adjusted estimates. SETTING: Ontario, Canada. PARTICIPANTS: A population-based cohort of all private households with index cases. We excluded cases in congregate settings, as well as households with one individual or with >1 case with the same earliest symptom onset date. EXPOSURE: VOC status, defined as either individuals confirmed as B.1.1.7 using whole genome sequencing or those that screened positive for the N501Y mutation using real-time PCR. MAIN OUTCOME AND MEASURE: Household secondary attack rate, defined as the number of household secondary cases that occurred 1-14 days after the index case divided by the total number of household secondary contacts. RESULTS: We included 1,259 index VOC and non-VOC cases in the propensity score-matched analysis. The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49), similar to the unadjusted estimate. In stratified analyses, the higher secondary attack rate for VOC compared to non-VOC index cases was accentuated for asymptomatic index cases (RR=1.91, 95% CI 0.96-3.80) and presymptomatic cases (RR=3.41, 95%CI 1.13-10.26) CONCLUSIONS AND RELEVANCE: This study provides strong evidence of increased transmissibility in households due to VOCs and suggests that asymptomatic and pre-symptomatic transmission may be of particular importance for VOCs. Our study suggests that more aggressive public health measures will be needed to control VOCs and that ongoing research is needed to understand mechanisms of VOC transmissibility to curb their associated morbidity and mortality.
{"title":"Increased Household Secondary Attacks Rates With Variant of Concern Severe Acute Respiratory Syndrome Coronavirus 2 Index Cases","authors":"S. Buchan, S. Tibebu, N. Daneman, M. Whelan, T. Vanniyasingam, M. Murti, K. Brown","doi":"10.1101/2021.03.31.21254502","DOIUrl":"https://doi.org/10.1101/2021.03.31.21254502","url":null,"abstract":"IMPORTANCE: Higher secondary attack rates related to variant of concern (VOC) index cases have been reported, but have not been explored within households, which continue to be an important source of coronavirus disease 2019 (COVID-19) transmission OBJECTIVE: To compare secondary attack rates in households with VOC versus non-VOC index cases. DESIGN: A retrospective cohort study of household index cases reported from February 7-27, 2021. A propensity-score matched cohort was derived to calculate adjusted estimates. SETTING: Ontario, Canada. PARTICIPANTS: A population-based cohort of all private households with index cases. We excluded cases in congregate settings, as well as households with one individual or with >1 case with the same earliest symptom onset date. EXPOSURE: VOC status, defined as either individuals confirmed as B.1.1.7 using whole genome sequencing or those that screened positive for the N501Y mutation using real-time PCR. MAIN OUTCOME AND MEASURE: Household secondary attack rate, defined as the number of household secondary cases that occurred 1-14 days after the index case divided by the total number of household secondary contacts. RESULTS: We included 1,259 index VOC and non-VOC cases in the propensity score-matched analysis. The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49), similar to the unadjusted estimate. In stratified analyses, the higher secondary attack rate for VOC compared to non-VOC index cases was accentuated for asymptomatic index cases (RR=1.91, 95% CI 0.96-3.80) and presymptomatic cases (RR=3.41, 95%CI 1.13-10.26) CONCLUSIONS AND RELEVANCE: This study provides strong evidence of increased transmissibility in households due to VOCs and suggests that asymptomatic and pre-symptomatic transmission may be of particular importance for VOCs. Our study suggests that more aggressive public health measures will be needed to control VOCs and that ongoing research is needed to understand mechanisms of VOC transmissibility to curb their associated morbidity and mortality.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86978529","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 : 2021-03-26DOI: 10.1101/2021.03.22.21254109
D. Tully, J. Hahn, D. J. Bean, J. Evans, M. Morris, K. Page, Todd M. Allen
Background. The current opioid epidemic across the United States has fueled a surge in the rate of new HCV infections among young persons who inject drugs (PWIDs). Paramount to interrupting transmission is targeting these high-risk populations and understanding the underlying network structures facilitating transmission within these communities. Methods. Deep sequencing data were obtained for 52 participants from 32 injecting partnerships enrolled in the UFO Partner Study which is a prospective study of self-described injecting dyad partnerships from a large community-based study of HCV infection in young adult PWIDs from San Francisco. Phylogenetically linked transmission events were identified using traditional genetic-distance measures and viral deep sequence phylogenies reconstructed to determine the statistical support of inferences and the direction of transmission within partnerships. Results. Using deep sequencing data, we found that 12 of 32 partnerships were genetically similar and clustered. Three additional phylogenetic clusters were found describing novel putative transmission links outside of the injecting relationship. Transmission direction was inferred correctly for five partnerships with the incorrect transmission direction inferred in more than 50% of cases. Notably, we observed that phylogenetic linkage was most often associated with a lower number of network partners and involvement in a sexual relationship.
{"title":"IDENTIFICATION OF GENETICALLY RELATED HCV INFECTIONS AMONG SELF-DESCRIBED INJECTING PARTNERSHIPS","authors":"D. Tully, J. Hahn, D. J. Bean, J. Evans, M. Morris, K. Page, Todd M. Allen","doi":"10.1101/2021.03.22.21254109","DOIUrl":"https://doi.org/10.1101/2021.03.22.21254109","url":null,"abstract":"Background. The current opioid epidemic across the United States has fueled a surge in the rate of new HCV infections among young persons who inject drugs (PWIDs). Paramount to interrupting transmission is targeting these high-risk populations and understanding the underlying network structures facilitating transmission within these communities. Methods. Deep sequencing data were obtained for 52 participants from 32 injecting partnerships enrolled in the UFO Partner Study which is a prospective study of self-described injecting dyad partnerships from a large community-based study of HCV infection in young adult PWIDs from San Francisco. Phylogenetically linked transmission events were identified using traditional genetic-distance measures and viral deep sequence phylogenies reconstructed to determine the statistical support of inferences and the direction of transmission within partnerships. Results. Using deep sequencing data, we found that 12 of 32 partnerships were genetically similar and clustered. Three additional phylogenetic clusters were found describing novel putative transmission links outside of the injecting relationship. Transmission direction was inferred correctly for five partnerships with the incorrect transmission direction inferred in more than 50% of cases. Notably, we observed that phylogenetic linkage was most often associated with a lower number of network partners and involvement in a sexual relationship.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"9 34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91143573","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 : 2021-03-20DOI: 10.1101/2021.03.17.21250449
G. Bosslet, M. Pollak, J. Jang, Rebekah L. Roll, Marko Sperling, Babar Khan
Background: The effect of in person primary and secondary school instruction on the community transmission of SARS-CoV-2 remains unclear. Objective: To determine the county-level effect of in-person primary and secondary school reopening on daily cases of SARS-CoV-2 in Indiana. Design: Panel data regression analysis utilizing the proportion of in-person learning to evaluate an association with community-wide daily new SARS-CoV-2 cases. The study period was July 12-October 6, 2020. Setting: A county-level population-based study. Participants: We included 73 out of 92 (79.3%) Indiana Counties in the analysis, accounting for 85.7% of school corporations and 90.6% of student enrollement statewide. Main outcomes and measures: The primary exposure was the proportion of students returning to in-person instruction. The primary outcome was the daily new SARS-CoV-2 cases per 100,000 residents at the county level. Results: There is a statistically significant relationship between the proportion of students attending K-12 schools in-person and the county level daily cases of SARS-CoV-2 28 days later. For all ages, the coefficient of interest ({beta}) is estimated at 3.36 (95% CI: 1.91-4.81; p < 0.001). This coefficient represents the effect of a change the proportion of students attending in-person on new daily cases 28 days later. For example, a 10 percentage point increase in K-12 students attending school in-person is associated with a daily increase in SARS-CoV-2 cases in the county equal to 0.336 cases/100,000 residents of all ages. Limitations: Single state study; inability to stratify school age effects by age; cannot account for non-linear growth effects. Conclusion and relevance: In-person primary and secondary school is associated with a statistically significant but proportionally small increase in the spread of SARS-CoV-2 cases.
{"title":"The effect of in-person primary and secondary school instruction on county-level SARS-CoV-2 spread in Indiana","authors":"G. Bosslet, M. Pollak, J. Jang, Rebekah L. Roll, Marko Sperling, Babar Khan","doi":"10.1101/2021.03.17.21250449","DOIUrl":"https://doi.org/10.1101/2021.03.17.21250449","url":null,"abstract":"Background: The effect of in person primary and secondary school instruction on the community transmission of SARS-CoV-2 remains unclear. Objective: To determine the county-level effect of in-person primary and secondary school reopening on daily cases of SARS-CoV-2 in Indiana. Design: Panel data regression analysis utilizing the proportion of in-person learning to evaluate an association with community-wide daily new SARS-CoV-2 cases. The study period was July 12-October 6, 2020. Setting: A county-level population-based study. Participants: We included 73 out of 92 (79.3%) Indiana Counties in the analysis, accounting for 85.7% of school corporations and 90.6% of student enrollement statewide. Main outcomes and measures: The primary exposure was the proportion of students returning to in-person instruction. The primary outcome was the daily new SARS-CoV-2 cases per 100,000 residents at the county level. Results: There is a statistically significant relationship between the proportion of students attending K-12 schools in-person and the county level daily cases of SARS-CoV-2 28 days later. For all ages, the coefficient of interest ({beta}) is estimated at 3.36 (95% CI: 1.91-4.81; p < 0.001). This coefficient represents the effect of a change the proportion of students attending in-person on new daily cases 28 days later. For example, a 10 percentage point increase in K-12 students attending school in-person is associated with a daily increase in SARS-CoV-2 cases in the county equal to 0.336 cases/100,000 residents of all ages. Limitations: Single state study; inability to stratify school age effects by age; cannot account for non-linear growth effects. Conclusion and relevance: In-person primary and secondary school is associated with a statistically significant but proportionally small increase in the spread of SARS-CoV-2 cases.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86886263","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 : 2021-03-20DOI: 10.1101/2021.03.19.21253889
A. Leidi, F. Koegler, R. Dumont, Richard Dubos, M. Zaballa, G. Piumatti, M. Coen, Amandine Berner, P. Darbellay Farhoumand, P. Vetter, N. Vuilleumier, L. Kaiser, D. Courvoisier, A. Azman, I. Guessous, S. Stringhini
Importance: Serological assays detecting specific IgG antibodies generated against the Spike protein following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. Objective: To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositiveindividuals from a population-based sample as compared to seronegative controls. Design: Retrospective longitudinal propensity-score matched cohort study. Setting: A seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections since the beginning of the pandemic. Participants: Participants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index, smoking status and education level. Exposure: SARS-CoV-2 seropositivity. Main outcomes and measures: Our primary outcome was virologically confirmed SARS-CoV-2 infections which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevance: Seroconversion after SARS-CoV-2 infection confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.
{"title":"Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study","authors":"A. Leidi, F. Koegler, R. Dumont, Richard Dubos, M. Zaballa, G. Piumatti, M. Coen, Amandine Berner, P. Darbellay Farhoumand, P. Vetter, N. Vuilleumier, L. Kaiser, D. Courvoisier, A. Azman, I. Guessous, S. Stringhini","doi":"10.1101/2021.03.19.21253889","DOIUrl":"https://doi.org/10.1101/2021.03.19.21253889","url":null,"abstract":"Importance: Serological assays detecting specific IgG antibodies generated against the Spike protein following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. Objective: To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositiveindividuals from a population-based sample as compared to seronegative controls. Design: Retrospective longitudinal propensity-score matched cohort study. Setting: A seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections since the beginning of the pandemic. Participants: Participants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index, smoking status and education level. Exposure: SARS-CoV-2 seropositivity. Main outcomes and measures: Our primary outcome was virologically confirmed SARS-CoV-2 infections which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevance: Seroconversion after SARS-CoV-2 infection confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77777377","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 : 2021-03-12DOI: 10.1101/2021.03.11.21253402
N. Antonio-Villa, L. Fernández-Chirino, J. Pisanty-Alatorre, J. Mancilla-Galindo, A. Kammar-García, A. Vargas-Vázquez, A. González-Díaz, C. A. Fermín-Martínez, A. Márquez-Salinas, E. Canedo Guerra, J. Bahena-López, M. Villanueva-Reza, J. Márquez-Sánchez, M. E. Jaramillo-Molina, L. Gutiérrez-Robledo, Omar Yaxmehen Bello-Chavolla
The impact of the COVID-19 pandemic in Mexico City has been sharp, as several social inequalities coexist with chronic comorbidities. Here, we conducted an in-depth evaluation of the impact of social, municipal, and individual factors on the COVID-19 pandemic in working-age population living in Mexico City. To this end, we used data from the National Epidemiological Surveillance System; furthermore, we used a multidimensional metric, the social lag index (DISLI), to evaluate its interaction with mean urban population density (MUPD) and its impact on COVID-19 rates. Influence DISLI and MUPD on the effect of vehicular mobility policies on COVID-19 rates were also tested. Finally, we assessed the influence of MUPD and DISLI on discrepancies of COVID-19 and non-COVID-19 excess mortality compared with death certificates from the General Civil Registry. We detected vulnerable groups who belonged to economically active sectors and who experienced increased risk of adverse COVID-19 outcomes. The impact of social inequalities transcends individuals and has significant effects at a municipality level, with and interaction between DISLI and MUPD. Marginalized municipalities with high population density experienced an accentuated risk for adverse COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts across marginalized municipalities. Finally, we report an under-registry of COVID-19 deaths and significant excess mortality associated with non-COVID-19 deaths closely related to MUPD/DISLI in an ambulatory setting, which could be a negative externality of hospital reconversion. In conclusion, social, individual, and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.
{"title":"Comprehensive evaluation of the impact of sociodemographic inequalities on adverse outcomes and excess mortality during the COVID-19 pandemic in Mexico City","authors":"N. Antonio-Villa, L. Fernández-Chirino, J. Pisanty-Alatorre, J. Mancilla-Galindo, A. Kammar-García, A. Vargas-Vázquez, A. González-Díaz, C. A. Fermín-Martínez, A. Márquez-Salinas, E. Canedo Guerra, J. Bahena-López, M. Villanueva-Reza, J. Márquez-Sánchez, M. E. Jaramillo-Molina, L. Gutiérrez-Robledo, Omar Yaxmehen Bello-Chavolla","doi":"10.1101/2021.03.11.21253402","DOIUrl":"https://doi.org/10.1101/2021.03.11.21253402","url":null,"abstract":"The impact of the COVID-19 pandemic in Mexico City has been sharp, as several social inequalities coexist with chronic comorbidities. Here, we conducted an in-depth evaluation of the impact of social, municipal, and individual factors on the COVID-19 pandemic in working-age population living in Mexico City. To this end, we used data from the National Epidemiological Surveillance System; furthermore, we used a multidimensional metric, the social lag index (DISLI), to evaluate its interaction with mean urban population density (MUPD) and its impact on COVID-19 rates. Influence DISLI and MUPD on the effect of vehicular mobility policies on COVID-19 rates were also tested. Finally, we assessed the influence of MUPD and DISLI on discrepancies of COVID-19 and non-COVID-19 excess mortality compared with death certificates from the General Civil Registry. We detected vulnerable groups who belonged to economically active sectors and who experienced increased risk of adverse COVID-19 outcomes. The impact of social inequalities transcends individuals and has significant effects at a municipality level, with and interaction between DISLI and MUPD. Marginalized municipalities with high population density experienced an accentuated risk for adverse COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts across marginalized municipalities. Finally, we report an under-registry of COVID-19 deaths and significant excess mortality associated with non-COVID-19 deaths closely related to MUPD/DISLI in an ambulatory setting, which could be a negative externality of hospital reconversion. In conclusion, social, individual, and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"175 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83782267","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 : 2021-03-10DOI: 10.1101/2021.03.08.21253090
G. Ioannou, A. O’Hare, K. Berry, V. Fan, K. Crothers, M. Eastment, E. Locke, P. Green, Javeed A. Shah, J. Dominitz
Objectives: We aimed to describe trends in the incidence of adverse outcomes among patients who tested positive for SARS-CoV-2 between February and September 2020 within a national healthcare system. Setting: US Veterans Affairs national healthcare system. Participants: Enrollees in the VA healthcare system who tested positive for SARS-CoV-2 between 2/28/2020 and 9/30/2020 (n=55,952). Outcomes: Death, hospitalization, intensive care unit (ICU) admission and mechanical ventilation within 30 days of testing positive. The incidence of these outcomes was examined among patients infected each month and trends were evaluated using an interrupted time-series analysis. Results: Between February and July 2020, during the first wave of the US pandemic, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), with subsequent stabilization between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, and documented symptoms and after additional adjustment for laboratory test results among hospitalized patients, including among subgroups admitted to the ICU and treated with mechanical ventilation. Among hospitalized patients, use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%) vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) decreased while use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%) and remdesivir (1.7% to 45.4%) increased from February to September. Conclusions: Among patients who tested positive for SARS-CoV-2 in a large national US healthcare system, risk for a range of adverse outcomes decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics.
{"title":"Trends over time in the risk of adverse outcomes among patients with SARS-CoV-2 infection","authors":"G. Ioannou, A. O’Hare, K. Berry, V. Fan, K. Crothers, M. Eastment, E. Locke, P. Green, Javeed A. Shah, J. Dominitz","doi":"10.1101/2021.03.08.21253090","DOIUrl":"https://doi.org/10.1101/2021.03.08.21253090","url":null,"abstract":"Objectives: We aimed to describe trends in the incidence of adverse outcomes among patients who tested positive for SARS-CoV-2 between February and September 2020 within a national healthcare system. Setting: US Veterans Affairs national healthcare system. Participants: Enrollees in the VA healthcare system who tested positive for SARS-CoV-2 between 2/28/2020 and 9/30/2020 (n=55,952). Outcomes: Death, hospitalization, intensive care unit (ICU) admission and mechanical ventilation within 30 days of testing positive. The incidence of these outcomes was examined among patients infected each month and trends were evaluated using an interrupted time-series analysis. Results: Between February and July 2020, during the first wave of the US pandemic, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), with subsequent stabilization between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, and documented symptoms and after additional adjustment for laboratory test results among hospitalized patients, including among subgroups admitted to the ICU and treated with mechanical ventilation. Among hospitalized patients, use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%) vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) decreased while use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%) and remdesivir (1.7% to 45.4%) increased from February to September. Conclusions: Among patients who tested positive for SARS-CoV-2 in a large national US healthcare system, risk for a range of adverse outcomes decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics.","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":"2021-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77706455","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}
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