Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes

    Authors: Mayank Batra; Runxia Tian; Chongxu Zhang; Emile Clarence; Camila Sofia Sacher; Justin Nestor Miranda; Justin Rafa O De La Fuente; Megan Mathew; Desmond Green; Sayari Patel; Maria Virginia Perez Bastidas; Sara Haddadi; Mukunthan Murthi; Miguel Santiago Gonzalez; Shweta Kambali; Kayo HM Santos; Huda Asif; Farzaneh Modarresi; Mohammad Faghihi; Mehdi Mirsaeidi

    doi:10.1101/2020.09.23.20197251 Date: 2020-09-24 Source: medRxiv

    The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 MESHD (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum SERO of infected MESHD patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease MESHD has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including MICU admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum SERO IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea HP dyspnea MESHD were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum SERO of 55 (55%) patients at the time of admission. A high concentration of antibodies SERO, defined as signal to cut off ratio (S/Co)> 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio> 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection MESHD.

    Cross-reactive serum SERO and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection MESHD

    Authors: Ge Song; Wan-ting He; Sean Callaghan; Fabio Anzanello; Deli Huang; James Ricketts; Jonathan L. Torres; Nathan Beutler; Linghang Peng; Sirena Vargas; Jon Cassell; Mara Parren; Linlin Yang; Caroline Ignacio; Davey M. Smith; James E. Voss; David Nemazee; Andrew B. Ward; Thomas Rogers; Dennis R. Burton; Raiees Andrabi

    doi:10.1101/2020.09.22.308965 Date: 2020-09-23 Source: bioRxiv

    Pre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody SERO responses to SARS-CoV-2, either induced in natural infection MESHD or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection MESHD is to understand the nature and extent of cross-reactivity in humans to coronaviruses. We compared serum SERO antibody SERO and memory B cell responses to coronavirus spike (S) proteins from pre-pandemic and SARS-CoV-2 convalescent donors using a series of binding and functional assays. We found weak evidence of pre-existing SARS-CoV-2 cross-reactive serum SERO antibodies SERO in pre-pandemic donors. However, we found stronger evidence of pre-existing cross-reactive memory B cells that were activated on SARS-CoV-2 infection MESHD. Monoclonal antibodies SERO (mAbs) isolated from the donors showed varying degrees of cross-reactivity with betacoronaviruses, including SARS and endemic coronaviruses. None of the cross-reactive mAbs were neutralizing except for one that targeted the S2 subunit of the S protein. The results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody SERO responses to SARS-CoV-2.

    Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

    Authors: Anwar M Hashem; Abdullah Algaissi; Sarah A Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Sawsan S Alamri; Khalid A Alluhaybi; Haya I Hobani; Rahaf H AlHarbi; Reem M Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K Alharbi; Rowa Y Alhabbab; Ahdab A AlSaieedi; Wesam H Abdulaal; Abdullah Bukhari; Afrah A AL-Somali; Fadwa S Alofi; Asim A Khogeer; Arnab Pain; Almohanad A Alkayyal; Naif AM Almontashiri; Ahmad B Mahmoud; Xuguang Li; Sarah Dorothea Müller; Uwe Gerd Liebert; Naveed Ishaque; Lars Kaderali; Leif Erik Sander; Sven Laudi; Christian Drosten; Roland Eils; Christian Conrad; Ulf Landmesser; Irina Lehmann

    doi:10.1101/2020.09.21.20198309 Date: 2020-09-23 Source: medRxiv

    The Coronavirus Disease MESHD 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection MESHD. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies SERO (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies SERO. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies SERO were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies SERO, particularly anti-N IgG and IgM in the first 15 days after symptoms onset TRANS, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody SERO responses in COVID-19 patients with different disease severity.

    Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to SARS-CoV-2 severity

    Authors: Tom G Richardson; Si Fang; Ruth E Mitchell; Michael V Holmes; George Davey Smith; Dominik Schulz; Ulrich Mayr; Jochen Schneider; Christoph Spinner; Fabian Geisler; Roland M. Schmid; Tobias Lahmer; Wolfgang Huber; Xiushan Yin; Arsen Arakelyan; Denise Haslwanter; Rohit Jangra; Alev Celikgil; Duncan Kimmel; James H Lee; Margarette Mariano; Antonio Nakouzi; Jose Quiroz; Johanna Rivera; Wendy A Szymczak; Karen Tong; Jason Barnhill; Mattias NE Forsell; Clas Ahlm; Daniel T. Stein; Liise-anne Pirofski; Doctor Y Goldstein; Scott J. Garforth; Steven C. Almo; Johanna P. Daily; Michael B. Prystowsky; James D. Faix; Amy S. Fox; Louis M. Weiss; Jonathan R. Lai; Kartik Chandran

    doi:10.1101/2020.09.10.20191932 Date: 2020-09-11 Source: medRxiv

    Background: Developing insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease MESHD 2019 (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2. Methods: We applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence SARS-CoV-2 severity. Findings: In total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity SERO analyses. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P=2.19x10-16) and interleukin-1 receptor antagonist (IVW Beta=0.23, 95% CI=0.17 to 0.30, P=9.04x10-12). Further analyses using multivariable MR provided evidence that the effect of BMI on lowering immunoglobulin G, an antibody SERO class involved in protecting the body from infection MESHD, is substantially mediated by raised triglycerides levels (IVW Beta=-0.18, 95% CI=-0.25 to -0.12, P=2.32x10-08, proportion mediated=44.1%). The strongest evidence that any of the circulating proteins highlighted by our initial analysis influence SARS-CoV-2 severity was identified for soluble glycoprotein 130 (odds ratio=1.81, 95% CI=1.25 to 2.62, P=0.002), a signal transductor for interleukin-6 type cytokines which are involved in the bodys inflammatory response. However, based on current case samples for severe SARS-CoV-2 we were unable to replicate findings in independent samples. Interpretation: Our findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 are warranted to help elucidate therapeutic strategies for covid-19 disease severity.

    Antibody SERO Responses to SARS-CoV-2 in Coronavirus Diseases MESHD 2019 Patients with Different Severity

    Authors: Ekasit Kowitdamrong; Thanyawee Puthanakit; Watsamon Jantarabenjakul; Eakachai Prompetchara; Pintip Suchartlikitwong; Opass Putcharoen; Nattiya Hirankarn; Ke Lan; Yu Chen; Huabin Zhao

    doi:10.1101/2020.09.06.20189480 Date: 2020-09-08 Source: medRxiv

    Background: More understanding of antibody SERO responses in the SARS-CoV-2 infected MESHD population is useful for vaccine development. Aim: To investigate SARS-CoV-2 IgA MESHD and IgG among COVID-19 Thai patients with different severity. Methods: We used plasma SERO from 118 adult TRANS patients who have confirmed SARS-CoV-2 infection MESHD and 49 patients under investigation without infection MESHD, 20 patients with other respiratory infections MESHD, and 102 healthy controls. Anti-SARS-CoV-2 IgA and IgG were performed by enzyme-linked immunosorbent assay SERO from Euroimmun. The optical density ratio cut off for positive test was 1.1 for IgA and 0.8 for IgG. The association of antibody SERO response with the severity of diseases and the day of symptoms was performed. Results: From Mar 10 to May 31, 2020, 289 participants were enrolled, and 384 samples were analyzed. Patients were categorized by clinical manifestations to mild (n=59), moderate (n=27) and severe (n=32). The overall sensitivity SERO of IgA and IgG from samples collected after day 7 is 87.9% (95% CI 79.8-93.6) and 84.8% (95% CI 76.2-91.3), respectively. The severe group had a significantly higher level of specific IgA and IgG to S1 antigen compared to the mild group. All moderate to severe patients have specific IgG while 20% of the mild group did not have any IgG detected after two weeks. Interestingly, SARS-CoV-2 IgG level was significantly higher in males TRANS compared to females TRANS among the severe group (p=0.003). Conclusion: The serologic test SERO for SARS-CoV-2 has high sensitivity SERO after the second week after onset of illness. Serological response differs among patients with different severity and different sex.

    Spatial Distribution and Time Series Analysis of COVID-19 Pandemic in Italy: A Geospatial Perspective

    Authors: Muhammad Farhan Ul Moazzam; Tamkeen Urooj Paracha; Ghani Rahman; Byung Gul Lee; Nasir Farid; Adnan Arshad

    doi:10.21203/rs.3.rs-73628/v1 Date: 2020-09-07 Source: ResearchSquare

    The novel coronavirus pandemic disease MESHD (COVID-19) affected the whole globe, though there is lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of COVID-19 infected MESHD patients show mild to moderate symptoms and they get better without any medical assistance due to better immune system to generate antibodies SERO against the novel coronavirus. In this study the active cases, serious cases, recovered cases, deaths MESHD and total confirmed cases TRANS have been analyzed using geospatial technique (IDW) with the time span of 2nd March to 3rd June 2020. As on 3rd June the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951 and active cases were 39,177 which has been reported by the Ministry of health, Italy. March 2nd – June 3rd 2020 a sum of 231, 238 cases has been reported in Italy out of which 38.68% cases reported in Lombardia region with death rate of 18% which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%) and Trento (84.54%).  The COVID-19 evolution in Italy has been particularly found in the major urban area i.e. Rome, Milan, Naples, Bologna and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and the recovered cases. Thus, monitoring and planning using geospatial technique is very important to control COVID-19 spread in the country.

    Analyzing inherent biases in SARS-CoV-2 PCR and serological epidemiologic metrics

    Authors: Monia Makhoul; Farah Abou-Hijleh; Shaheen Seedat; Ghina R Mumtaz; Hiam Chemaitelly; Houssein Ayoub; Laith J Abu-Raddad; Xiaojian Liu; Wei Gao; Renli Zhang; Qiru Su; Andrew Azman; Justin Lessler; Xuan Zou; Wenfeng Gong; Brenda Clemente; Jerel Vega; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.30.20184705 Date: 2020-09-02 Source: medRxiv

    Abstract Background: Prospective observational data show that infected persons with the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) remain polymerase chain reaction (PCR) positive for a prolonged duration, and that detectable antibodies SERO develop slowly with time. We aimed to analyze how these effects can bias key epidemiological metrics used to track and monitor SARS-CoV-2 epidemics. Methods: An age TRANS-structured mathematical model was constructed to simulate progression of SARS-CoV-2 epidemics in populations. PCR testing to diagnose infection MESHD and cross-sectional surveys to measure seroprevalence SERO were also simulated. Analyses were conducted on simulated outcomes assuming a natural epidemic time course and an epidemic in presence of interventions. Results: The prolonged PCR positivity biased the epidemiological measures. There was a lag of 10 days between the true epidemic peak and the actually-observed peak. Prior to epidemic peak, PCR positivity rate was 2-fold higher than that based only on current active infection MESHD, and half of those tested positive by PCR were in the prolonged PCR positivity stage after infection clearance. Post epidemic peak, PCR positivity rate poorly predicted true trend in active infection MESHD. Meanwhile, the prolonged PCR positivity did not appreciably bias estimation of the basic reproduction number TRANS R0 TRANS. The time delay in development of detectable antibodies SERO biased measured seroprevalence SERO. The actually-observed seroprevalence SERO substantially underestimated true prevalence SERO of ever infection MESHD, with the underestimation being most pronounced around epidemic peak. Conclusions: Caution is warranted in interpreting PCR and serological testing SERO data, and any drawn inferences need to factor the effects of the investigated biases for an accurate assessment of epidemic dynamics.

    Prevalence SERO of SARS-CoV-2 Infections MESHD in a Pediatric Orthopedic Hospital

    Authors: Ghalib Bardai; Jean A Ouellet; Thomas Engelhardt; Gianluca Bertolizio; Zenghui Wu; Frank Rauch; Reinaldo E Fernandez; Owen R Baker; Morgan Keruly; Charles S Kirby; Ethan Klock; Kirsten Littlefield; Jernelle Miller; Haley A Schmidt; Philip Sullivan; Estelle Piwowar-Manning; Ruchee Shrestha; Andrew D Redd; Richard Eric Rothman; David J Sullivan; Shmuel Shoham; Arturo Casadevall; Thomas C. Quinn; Andrew Pekosz; Aaron AR Tobian; Oliver Laeyendecker; William Damsky; David van Dijk; Alfred Ian Lee; Hyung Chun; Akhil Vaid; Guillermo Barturen; Scott R. Tyler; Hardik Shah; Yinh-chih Wang; Shwetha Hara Sridhar; Juan Soto; Swaroop Bose; Kent Madrid; Ethan Ellis; Elyze Merzier; Konstantinos Vlachos; Nataly Fishman; Manying Tin; Melissa Smith; Hui Xie; Manishkumar Patel; Kimberly Argueta; Jocelyn Harris; Neha Karekar; Craig Batchelor; Jose Lacunza; Mahlet Yishak; Kevin Tuballes; Leisha Scott; Arvind Kumar; Suraj Jaladanki; Ryan Thompson; Evan Clark; Bojan Losic; - The Mount Sinai COVID-19 Biobank Team; Jun Zhu; Wenhui Wang; Andrew Kasarskis; Benjamin S. Glicksberg; Girish Nadkarni; Dusan Bogunovic; Cordelia Elaiho; Sandeep Gangadharan; George Ofori-Amanfo; Kasey Alesso-Carra; Kenan Onel; Karen M. Wilson; Carmen Argmann; Marta E. Alarcón-Riquelme; Thomas U. Marron; Adeeb Rahman; Seunghee Kim-Schulze; Sacha Gnjatic; Bruce D. Gelb; Miriam Merad; Robert Sebra; Eric E. Schadt; Alexander W. Charney

    doi:10.1101/2020.08.31.20183533 Date: 2020-09-02 Source: medRxiv

    This project assessed the prevalence SERO of active and past infection with severe HP infection with severe MESHD acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in a specialized pediatric institution that did not provide care for coronavirus disease MESHD 2019 (Covid-19). The study was performed in Montreal, the city with the highest number of Covid-19 cases in Canada during the early phase of the pandemic. Testing for SARS-CoV-2 RNA in 199 individuals (39 children TRANS, 61 accompanying persons, 99 hospital employees) did not reveal active infection in any of the study participants. However, 22 (11%) of study participants had SARS-CoV-2 IgG antibodies SERO, indicating prior infection MESHD. Ten of these participants did not report symptoms compatible with Covid-19 in the 6 months prior to the study. Thus, although no evidence for active infection MESHD was found within the institution, consideration should be given to regular staff testing to detect asymptomatic TRANS spreading of SARS-CoV-2. In addition, it could be useful to test accompanying persons in children TRANS presenting for surgical procedures.

    Seroprevalence SERO and immunity of SARS-CoV-2 infection MESHD in children TRANS and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study

    Authors: Agne Ulyte; Thomas Radtke; Irene Abela; Sarah H Haile; Julia Braun; Ruedi Jung; Christoph Berger; Alexandra Trkola; Jan Fehr; Milo A Puhan; Susi Kriemler; Anel Nurtay; Lucie Abeler-Dörner; David G Bonsall; Michael V McConnell; Shawn O'Banion; Christophe Fraser; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.30.20184671 Date: 2020-09-02 Source: medRxiv

    Introduction Seroprevalence SERO and transmission TRANS routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in children TRANS and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence SERO of SARS-CoV-2 antibodies SERO in school-attending children TRANS repeatedly. It will examine risk factors for infection MESHD, relationship between seropositivity and symptoms, and temporal persistence of antibodies SERO. Additionally, it will include testing of school personnel and parents TRANS. Methods and analysis The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children TRANS aged TRANS 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood MESHD blood SERO and saliva samples are collected for SARS-CoV-2 serological testing SERO after the first wave of infections (June/July 2020), in fall HP (October/November 2020), and after winter (March/April 2021). Venous blood MESHD blood SERO is also collected for serological testing SERO of parents TRANS and school personnel. Bi-monthly questionnaires to children TRANS, parents TRANS and school personnel cover SARS-CoV-2 symptoms MESHD and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence SERO and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity SERO and specificity of the serological test SERO in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and dissemination The study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717.

    Analyzing inherent biases in SARS-CoV-2 PCR and serological epidemiologic metrics

    Authors: Monia Makhoul; Farah Abou-Hijleh; Shaheen Seedat; Ghina R Mumtaz; Hiam Chemaitelly; Houssein Ayoub; Laith J. Abu-Raddad

    doi:10.21203/rs.3.rs-70006/v1 Date: 2020-09-01 Source: ResearchSquare

    Background Prospective observational data show that infected persons with the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) remain polymerase chain reaction (PCR) positive for a prolonged duration, and that detectable antibodies SERO develop slowly with time. We aimed to analyze how these effects can bias key epidemiological metrics used to track and monitor SARS-CoV-2 epidemics.Methods An age TRANS-structured mathematical model was constructed to simulate progression of SARS-CoV-2 epidemics in populations. PCR testing to diagnose infection MESHD and cross-sectional surveys to measure seroprevalence SERO were also simulated. Analyses were conducted on simulated outcomes assuming a natural epidemic time course and an epidemic in presence of interventions.Results The prolonged PCR positivity biased the epidemiological measures. There was a lag of 10 days between the true epidemic peak and the actually-observed peak. Prior to epidemic peak, PCR positivity rate was 2-fold higher than that based only on current active infection MESHD, and half of those tested positive by PCR were in the prolonged PCR positivity stage after infection clearance. Post epidemic peak, PCR positivity rate poorly predicted true trend in active infection MESHD. Meanwhile, the prolonged PCR positivity did not appreciably bias estimation of the basic reproduction number TRANS R0 TRANS. The time delay in development of detectable antibodies SERO biased measured seroprevalence SERO. The actually-observed seroprevalence SERO substantially underestimated true prevalence SERO of ever infection MESHD, with the underestimation being most pronounced around epidemic peak.Conclusions Caution is warranted in interpreting PCR and serological testing SERO data, and any drawn inferences need to factor the effects of the investigated biases for an accurate assessment of epidemic dynamics.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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