scholarly journals Waning of SARS-CoV-2 antibodies targeting the Spike protein in individuals post second dose of ChAdOx1 and BNT162b2 COVID-19 vaccines and risk of breakthrough infections: analysis of the Virus Watch community cohort.

2021 ◽  
Author(s):  
Robert William Aldridge ◽  
Alexei Yavlinsky ◽  
Vincent Grigori Nguyen ◽  
Max T Eyre ◽  
Madhumita Shrotri ◽  
...  
Keyword(s):  
Severe Disease ◽  
Vaccine Dose ◽  
Antibody Test ◽  
The Elderly ◽  
Spike Protein ◽  
Control Analysis ◽  
Correlate Of Protection ◽  
Increased Risk ◽  
Log Linear ◽  
Case Control Analysis

Background: SARS-CoV-2 vaccines stimulate production of antibodies targeting the spike protein (anti-S). The level of antibodies following vaccination and trajectories of waning may differ between vaccines influencing the level of protection, how soon protection is reduced and, consequently the optimum timing of booster doses. Methods: We measured SARS-CoV-2 anti-S titre in the context of seronegativity for SARS-CoV-2 anti-Nucleocapsid (anti-N), in samples collected between 1st July and 24th October 2021 in a subset of adults in the Virus Watch community cohort. We compared anti-S levels after BNT162b2 (BioNTech/Pfizer) or ChAdOx1 (AstraZeneca/Oxford) vaccination using time since second dose of vaccination, age, sex and clinical vulnerability to investigate antibody waning. To investigate the use of anti-S levels as a correlate of protection against SARS-CoV-2 infection, we undertook a survival analysis (Kaplan-Meier and Cox) with individuals entering 21 days after their second dose of vaccine, or first antibody test after 1st July (whichever was latest) and exiting with the outcome of SARS-Cov-2 infection or at the end of follow up 24th October 2021. We also undertook a negative test design case-control analysis of infections occurring after the second vaccine dose (breakthrough infections) to determine whether the type of vaccine affected the risk of becoming infected. Results: 24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, p<0.001). Discussion: Anti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates we would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2. Our results showing an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with our data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2. Our data demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.

Abstract 357: DNA Methylation Profiles of African American Val122Ile-Transthyretin Mutation Carriers Reveals Genes Involved in Amyloidosis Regulation

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Gita Pathak ◽  
Frank Wendt ◽  
Antonella De Lillo ◽  
Yari Nunez ◽  
Aranyak Goswami ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Heart Disease ◽  
Hippocampal Neurons ◽  
Cardiac Fibrosis ◽  
African Descent ◽  
Amyloid Deposition ◽  
Control Analysis ◽  
Increased Risk ◽  
Altered Gene ◽  
Case Control Analysis

The Transthyretin ( TTR ) Val122Ile mutation causes a rare life-threatening disorder attributable to amyloid deposition. This mutation is mainly present in people of African descent; carriers have an increased risk of congestive heart failure and several other non-cardiac phenotypes such as carpal tunnel syndrome, peripheral edema, and arthroplasty. Cardiac disease in Val122Ile carriers may not depend solely on this mutation and other uninvestigated factors could contribute to clinical heterogeneity. One possible mechanism is through DNA methylation, the addition of a methyl group on CG-dinucleotides, which can result in altered gene expression. We investigated methylation changes contributing to heart disease in Val122Ile carriers to identify non-TTR regulatory mechanisms. We investigated 96 Val122Ile carriers of genetically-confirmed African descent using the Illumina EPIC array, which covers 850,000 methylation sites across the genome. We found changes in five methylated sites associated with heart disease. These map to FAM129B, SKI, WDR27, GLS , and an intergenic site near RP11-550A5.2 (p=1.6 to 4.6e-8), and a methylated region containing KCNA6 and GALNT3 (p=1.1e-12). Weighted methylated sites mapped to PPI network analysis identified ABCA1 gene (p=0.001). We also found six cis-mQTLs associated with the FAM129B CpG site (p=4.1e-24 to 2.8e-14). We replicated two of the aforementioned CpG sites near RP11-550A5.2 (p=0.021) and in FAM129B (p=0.016) at nominal significance in a case-control analysis of confirmed cases of TTR amyloidosis. GLS encodes glutaminase, which catalyzes the conversion of glutamine to glutamate. Its expression is increased in amyloid-beta neurons and neurofibrillary tangles. ABCA1 regulates cholesterol transport and interacts with APOA1 and APP ; its dysregulation increases amyloid deposition. Increasing FAM129B expression improves the clearance of amyloid deposits and rescues hippocampal neurons from apoptosis. The SKI expression modulates TGF-beta , resulting in cardiac fibrosis. Of note, SKI and FAM129B together are involved in the regularion of various muscle tissues. Collectively, these findings suggest that a complex amyloid-related gene circuit could explain diverse symptoms in Val122Ile carriers.

Case-Control Analysis of Cochlear Implant Performance in the Elderly

2009 ◽  
Vol 119 (S1) ◽  
pp. S126-S126
Author(s):  
Christina L. Runge-Samuelson ◽  
Humera F. Baig ◽  
Jamie W. Jensen ◽  
P. Ashley Wackym ◽  
David R. Friedland
Keyword(s):  
Cochlear Implant ◽  
The Elderly ◽  
Case Control ◽  
Control Analysis ◽  
Case Control Analysis

scholarly journals Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry

2009 ◽  
Vol 69 (2) ◽  
pp. 400-408 ◽  
Author(s):  
X Mariette ◽  
F Tubach ◽  
H Bagheri ◽  
M Bardet ◽  
J M Berthelot ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Inflammatory Diseases ◽  
Antibody Therapy ◽  
Case Control ◽  
Hodgkin's Lymphoma ◽  
Control Analysis ◽  
Barr Virus ◽  
Increased Risk ◽  
Epstein Barr ◽  
Case Control Analysis

Objective:To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents.Methods:A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case–control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference.Results:38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B cell and five T cell), five Hodgkin’s lymphoma (HL) and two Hodgkin’s-like lymphoma were collected. Epstein–Barr virus was detected in both of two Hodgkin’s-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4–1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case–control study: odds ratio 4.7 (1.3–17.7) and 4.1 (1.4–12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2).Conclusion:The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

scholarly journals Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination

2021 ◽  
Author(s):  
Meghan E. Garrett ◽  
Jared G. Galloway ◽  
Caitlin Wolf ◽  
Jennifer K. Logue ◽  
Nicholas Franko ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Vaccine Dose ◽  
Principal Component ◽  
Fusion Peptide ◽  
Antibody Binding ◽  
Spike Protein ◽  
Heptad Repeat ◽  
Medical Institute ◽  
Vaccine Type

ABSTRACTBackgroundControl of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination, including different vaccine platforms, is needed to achieve this goal.MethodsThe epitopes and pathways of escape for Spike-specific antibodies in individuals with diverse infection and vaccination history were profiled using Phage-DMS. Principal component analysis was performed to identify regions of antibody binding along the Spike protein that differentiate the samples from one another. Within these epitope regions we determined potential escape mutations by comparing antibody binding of peptides containing wildtype residues versus peptides containing a mutant residue.ResultsIndividuals with mild infection had antibodies that bound to epitopes in the S2 subunit within the fusion peptide and heptad-repeat regions, whereas vaccinated individuals had antibodies that additionally bound to epitopes in the N- and C-terminal domains of the S1 subunit, a pattern that was also observed in individuals with severe disease due to infection. Epitope binding appeared to change over time after vaccination, but other covariates such as mRNA vaccine dose, mRNA vaccine type, and age did not affect antibody binding to these epitopes. Vaccination induced a relatively uniform escape profile across individuals for some epitopes, whereas there was much more variation in escape pathways in in mildly infected individuals. In the case of antibodies targeting the fusion peptide region, which was a common response to both infection and vaccination, the escape profile after infection was not altered by subsequent vaccination.ConclusionsThe finding that SARS-CoV-2 mRNA vaccination resulted in binding to additional epitopes beyond what was seen after infection suggests protection could vary depending on the route of exposure to Spike antigen. The relatively conserved escape pathways to vaccine-induced antibodies relative to infection-induced antibodies suggests that if escape variants emerge, they may be readily selected for across vaccinated individuals. Given that the majority of people will be first exposed to Spike via vaccination and not infection, this work has implications for predicting the selection of immune escape variants at a population level.FundingThis work was supported by NIH grants AI138709 (PI Overbaugh) and AI146028 (PI Matsen). Julie Overbaugh received support as the Endowed Chair for Graduate Education (FHCRC). The research of Frederick Matsen was supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute and the Simons Foundation. Scientific Computing Infrastructure at Fred Hutch was funded by ORIP grant S10OD028685.

scholarly journals Subsequent Primary Malignancies Among Multiple Myeloma Patients Treated with or without Lenalidomide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2129-2129 ◽  
Author(s):  
Dana E Rollison ◽  
Rami Komrokji ◽  
Ji-Hyun Lee ◽  
Shalaka S Hampras ◽  
William Fulp ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stock Options ◽  
Research Funding ◽  
Case Control ◽  
Cancer Center ◽  
Control Analysis ◽  
Increased Risk ◽  
Case Control Analysis ◽  
Nested Case Control

Abstract Introduction: The incidence of subsequent primary malignancies (SPM) associated with lenalidomide treatment of multiple myeloma (MM) outside the context of maintenance therapy post-melphalan is unknown. Three clinical trials reported modest, statistically significant increased risks of SPM associated with lenalidomide treatment in MM patients (Palumbo et al, N Engl J Med, 2012; Attal et al, N Engl J Med, 2012; McCarthy et al, N Engl J Med, 2012). Although these randomized trials are well controlled for potential confounders, they represent a unique population of patients and a specific juxtaposition of lenalidomide use with melphalan; as such, their results are not necessarily generalizable to the broader MM patient population. To investigate whether lenalidomide is associated with an increased risk of SPM in MM patients within a clinical setting in the United States, we conducted a retrospective cohort study of 1,653 MM patients treated with or without lenalidomide at the Moffitt Cancer Center (“MCC”) in Tampa, FL. Methods: Patients treated for MM at MCC from 2004-2012 were identified through Moffitt's enterprise wide data warehouse combining clinical information from several sources, including the Cancer Registry, electronic medical records and disease-specific databases. Among 1,653 MM patients, ages 18 and older, 51 cases of SPM were verified by two hematologists for confirmation of MM and SPM diagnoses. Incidence rates and 95% confidence intervals (CI) for SPM were estimated using a Poisson distribution. Cox proportional hazards ratios (HR) and 95% CIs were calculated to estimate the age-adjusted association between lenalidomide treatment and SPM in the overall cohort, and stratified by ISS. Additional details on lenalidomide treatment and potential confounders were obtained through medical chart abstraction for SPM cases and a subset of MM patients from the baseline cohort who had not developed SPM; these controls were matched to cases 2:1 on age at MM diagnosis (+/- 5 years), gender, follow-up time (+/- 6 months), and date of diagnosis (+/- 1 year). Associations between lenalidomide and SPM in the nested case-control analysis were estimated using odds ratios (OR) and 95% CIs adjusted for age at MM diagnosis, bone marrow transplantation, creatinine levels and personal history of cancer. Results: Overall, 1,653 MM patients were followed for an average of 40 months, including patients treated with (n=846) or without (n=807) lenalidomide. Incident SPMs were observed for 15 patients treated with lenalidomide (0.55 per 100 person-years) and 36 patients treated without lenalidomide (1.27 per 100 person-years), corresponding to an HR of 0.44 (95% CI=0.24-0.80) (Figure 1). Of the 51 SPMs observed, 37 were solid tumors comprising 14 different types, including 9 and 28 in the lenalidomide and no lenalidomide groups, respectively (HR=0.55, 95% CI=0.15-0.69). Of the 14 hematological SPMs observed, 8 were in the lenalidomide group versus 6 in the no lenalidomide group (HR=0.90, 95%CI = 0.31-2.63). Similar associations between lenalidomide and SPM were observed for MM patients with ISS = 1 (HR=0.26, 95% CI=0.06-1.21) and for MM patients with ISS = 2 or 3 (HR=0.20, 95% CI=0.02-1.62). Of the 51 SPM cases and 102 matched controls included in the nested case-control analysis, 33.3% and 74.5% were treated with lenalidomide, respectively (adjusted OR=0.03, 95% CI=0.002-0.34). Similar associations were observed for lenalidomide given as part of first line treatment versus subsequent treatment, and for lenalidomide given alone or in combination with other drugs. (8 cases and 46 controls received melphalan in addition to lenalidomide.) There was no association between lenalidomide and SPM among those treated for >9.1 months (OR=0.05, 95% CI=0.01-0.43), the median treatment duration among controls. Conclusion: Lenalidomide treatment was not associated with an increased risk of SPM among a large cohort of MM patients. It is important to note that in this clinical setting (in 2004-2012) the use of lenalidomide in combination with melphalan and in the maintenance setting was a rare event. This may be a critical factor in the contrast between the results of this study and in the increase in SPMs reported in randomized clinical trials. Figure 1: Incidence of SPM among patients treated for MM with or without lenalidomide, Moffitt Cancer Center, 2004-2012 Figure 1:. Incidence of SPM among patients treated for MM with or without lenalidomide, Moffitt Cancer Center, 2004-2012 Disclosures Rollison: Celgene, Inc.: Research Funding. Off Label Use: Lenalidomide given as treatment for non-del(5q) MDS and/or multiple myeloma . Komrokji:Celgene: Consultancy, Research Funding. Lee:Celgene, Inc.: Research Funding. Hampras:Celgene, Inc: Research Funding. Fulp:Celgene, Inc.: Research Funding. Fisher:Celgene, Inc: Research Funding. Baz:Celgene: Research Funding; BMS: Research Funding; Millenium: Research Funding; Sanofi: Research Funding; Karyopharm: Research Funding. Olesnyckyj:Celgene: Employment, stock options Other. Kenvin:Celgene: Employment, stock options Other. Knight:Celgene, Inc: Employment, stock options Other. Dalton:Celgene, Inc.: Research Funding; Novartis: Consultancy, Honoraria; Genentech: Consultancy, Honoraria. Shain:L&M Healthcare/Onyx/Amgen: Research Funding, Speakers Bureau; Envision/Celgene: Research Funding, Speakers Bureau.

Infection following deep brain stimulator implantation performed in the conventional versus magnetic resonance imaging–equipped operating room

2009 ◽  
Vol 110 (2) ◽  
pp. 239-246 ◽  
Author(s):  
Alessandra Gorgulho ◽  
Catherine Juillard ◽  
Daniel Z. Uslan ◽  
Katayoun Tajik ◽  
Poorang Aurasteh ◽  
...  
Keyword(s):  
Los Angeles ◽  
Mr Imaging ◽  
Operating Room ◽  
Case Control ◽  
Control Analysis ◽  
Deep Brain Stimulator ◽  
Increased Risk ◽  
Significant Difference ◽  
Case Control Analysis ◽  
Deep Brain

Object Risk factors for deep brain stimulator (DBS) infection are poorly defined. Because DBS implants are not frequently performed in the MR imaging–equipped operating room (OR), no specific data about infection of DBS implants performed in the MR imaging environment are available in the literature. In this study the authors focus on the incidence of infection in patients undergoing surgery in the conventional versus MR imaging–equipped OR. Methods To identify cases of DBS-associated infection, the authors performed a retrospective cohort study with nested case-control analysis of all patients undergoing DBS implantation at the University of California Los Angeles Medical Center. Cases of DBS infection were identified using standardized clinical and microbiological criteria. Results Between January 1998 and September 2003, 228 DBSs were implanted. Forty-seven operations (20.6%) were performed in the conventional OR and 181 (79.4%) in the MR imaging–equipped OR. There was definite infection in 13 cases (5.7%) and possible infection in 7 cases (3%), for an overall infection rate of 8.7% (20 of 228 cases). There was no significant difference in infection rates in the conventional (7 [14.89%] of 47) versus MR imaging–equipped OR (13 [7.18%] of 181) (p = 0.7). Staphylococcus aureus was isolated in 62% of cases. Twelve of 13 confirmed cases underwent complete hardware removal. On case-control analysis, younger age (≤ 58.5 years) was a significant predictor of DBS infection (odds ratio 3.4, p = 0.027) Conclusions Infection is a serious complication of DBS implantation and commonly requires device removal for cure. The authors found that DBS implantation can be safely performed in MR imaging–equipped suites, possibly allowing improved lead placement. Young age was associated with an increased risk of DBS infection.

Preventing Fatalities in Building Bombings: What Can We Learn From the Oklahoma City Bombing?

2007 ◽  
Vol 1 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Mary T. Glenshaw ◽  
Jon S. Vernick ◽  
Guohua Li ◽  
Gary S. Sorock ◽  
Sheryll Brown ◽  
...  
Keyword(s):  
Progressive Collapse ◽  
Building Design ◽  
Oklahoma City ◽  
Epidemiological Methods ◽  
Control Analysis ◽  
Oklahoma City Bombing ◽  
Retrospective Case ◽  
Fatality Risk ◽  
Increased Risk ◽  
Case Control Analysis

ABSTRACTBackground: Bombings are an increasing threat to the public's health. Descriptive studies of blast injuries have been published, but these injuries have not been studied using analytical epidemiological methods. This study assesses factors associated with fatality risk among individuals exposed to the 1995 Oklahoma City bombing.Methods: Retrospective case-control analysis using multivariable logistic regression. Odds ratios (OR) of fatality are calculated among occupants of the Alfred P. Murrah Federal Building on April 19, 1995.Results: Of the 348 occupants exposed, 163 (46.8%) were fatally injured. Fatality risk was greatest in the collapsed region of the building (adjusted OR 176.7, 95% confidence interval [CI] 65.9–474.2). Age ≥40 was also associated with a significantly increased risk of fatality (OR 3.7, 95% CI 1.4–9.8). Among people found in the noncollapsed region of the building, employees' status compared to a visitor's or child's status was protective (OR 0.13, 95% CI 0.01–1.3)Conclusions: Structural collapse is the most important risk factor for fatality in a building bombing. Progressive collapse may be prevented through more supportive building design. Protection of vulnerable building occupants can be improved by placement of relevant facilities in more structurally reinforced areas. Regular evacuation training of personnel and clear egress routes may also reduce fatality in a building bombing. (Disaster Med Public Health Preparedness. 2007;1:27–33)

scholarly journals Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort study

EBioMedicine ◽  
2021 ◽  
Vol 64 ◽  
pp. 103216
Author(s):  
Sophie Lefèvre-Arbogast ◽  
Boris P Hejblum ◽  
Catherine Helmer ◽  
Christian Klose ◽  
Claudine Manach ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cognitive Decline ◽  
The Elderly ◽  
Case Control ◽  
Control Analysis ◽  
Case Control Analysis

Increased risk forCampylobacter jejuniandC. coliinfection of pet origin in dog owners and evidence for genetic association between strains causing infection in humans and their pets

2013 ◽  
Vol 141 (12) ◽  
pp. 2526-2535 ◽  
Author(s):  
L. MUGHINI GRAS ◽  
J. H. SMID ◽  
J. A. WAGENAAR ◽  
M. G. J. KOENE ◽  
A. H. HAVELAAR ◽  
...  
Keyword(s):  
Case Control ◽  
Control Analysis ◽  
Risk Of Infection ◽  
Source Attribution ◽  
Dog Ownership ◽  
Increased Risk ◽  
Sources Of Infection ◽  
Case Control Analysis ◽  
Sequence Types ◽  
Human Campylobacteriosis

SUMMARYWe comparedCampylobacter jejuni/colimultilocus sequence types (STs) from pets (dogs/cats) and their owners and investigated risk factors for pet-associated human campylobacteriosis using a combined source-attribution and case-control analysis. In total, 132/687 pet stools wereCampylobacter-positive, resulting in 499 strains isolated (320C. upsaliensis/helveticus, 100C. jejuni, 33C. hyointestinalis/fetus, 10C. lari, 4C. coli, 32 unidentified). There were 737 human and 104 petC. jejuni/colistrains assigned to 154 and 49 STs, respectively. Dog, particularly puppy, owners were at increased risk of infection with pet-associated STs. In 2/68 casesvs.0·134/68 expected by chance, a pet and its owner were infected with an identical ST (ST45, ST658). Although common sources of infection and directionality of transmission between pets and humans were unknown, dog ownership significantly increased the risk for pet-associated humanC. jejuni/coliinfection and isolation of identical strains in humans and their pets occurred significantly more often than expected.

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