Frank Esper

Cleveland Clinic

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Jeffrey S. Kahn

University of California, Davis

Carla Weibel

Yale University

Sarah Worley

Cleveland Clinic

Marie L. Landry

Yale University

Blanca E. Gonzalez

Universidad Autónoma de Guadalajara

David Ferguson

John Radcliffe Hospital

Daniel D. Rhoads

Case Western Reserve University

Jennifer S. Ko

Cleveland Clinic

Charles B. Foster

Cleveland Clinic

Gary W. Procop

Clinical and Laboratory Standards Institute

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Case Western Reserve University

100

Cleveland Clinic

Rainbow Babies & Children's Hospital

University School

University Hospitals of Cleveland

Cleveland Clinic Lerner College of Medicine

University Hospitals Case Medical Center

Boston Children's Hospital

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Pediatrics and Genetics

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Alpha to Omicron: Disease Severity and Clinical Outcomes of Major SARS-CoV-2 Variants

The Journal of Infectious Diseases (2022)

Frank Esper Thamali M. Adhikari Zheng Jin Tu Yu‐Wei Cheng Kim El-Haddad

Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited.Viral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio. Major variants were correlated with disease severity and patient outcomes.In total 2779 patients identified with either Alpha (n 1153), Gamma (n 122), Delta (n 808), or Omicron variants (n 696) were selected for analysis. No difference in frequency of hospitalization, intensive care unit (ICU) admission, and death were found among Alpha, Gamma, and Delta variants. However, patients with Omicron infection were significantly less likely to be admitted to the hospital, require oxygen, or admission to the ICU (2 12.8, P .001; 2 21.6, P .002; 2 9.6, P .01, respectively). In patients whose vaccination status was known, a substantial number had breakthrough infections with Delta or Omicron variants (218/808 [26.9] and 513/696 [73.7], respectively). In breakthrough infections, hospitalization rate was similar regardless of variant by multivariate analysis. No difference in disease severity was identified between Omicron subvariants BA.1 and BA.2.Disease severity associated with Alpha, Gamma, and Delta variants is comparable while Omicron infections are significantly less severe. Breakthrough disease is significantly more common in patients with Omicron infection.

2019-20 coronavirus outbreak

10.1093/infdis/jiac411

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Citations (114)

Rate and influence of respiratory virus co-infection on pandemic (H1N1) influenza disease

Journal of Infection (2011)

Frank Esper Timothy Spahlinger Lan Zhou

ObjectivesMany patients with influenza have more than one viral agent with co-infection frequencies reported as high as 20%. The impact of respiratory virus copathogens on influenza disease is unclear. We sought to determine if respiratory virus co-infection with pandemic H1N1 altered clinical disease.MethodsRespiratory samples from 229 and 267 patients identified with and without H1N1 influenza respectively were screened for the presence of 13 seasonal respiratory viruses by multiplex RT-PCR. Disease severity between coinfected and monoinfected H1N1 patients were quantified using a standardized clinical severity scale. Influenza viral load was calculated by quantitative RT-PCR.ResultsThirty (13.1%) influenza samples screened positive for the presence of 31 viral copathogens. The most prominent copathogens included rhinovirus (61.3%), and coronaviruses (16.1%). Median clinical severity of both monoinfected and coinfected groups were 1. Patients coinfected with rhinovirus tended to have lower clinical severity (median 0), whereas non-rhinovirus co-infections had substantially higher clinical severity (median 2). No difference in H1N1 viral load was observed between coinfected and monoinfected groups.ConclusionsRespiratory viruses co-infect patients with influenza disease. Patients coinfected with rhinovirus had less severe disease while non-rhinovirus co-infections were associated with substantially higher severity without changes in influenza viral titer.

Pandemic

H1N1 influenza

Pandemic influenza

Influenza pandemic

10.1016/j.jinf.2011.04.004

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Citations (116)

1064. Intra-Host SARS-CoV-2 Evolution Dynamics

Open Forum Infectious Diseases (2022)

Kim El Haddad Frank Esper Thamali Madhushani Adhikari Mudiyanselage Jing Li Tu Zheng

Abstract Background Our understanding of SARS-CoV-2 evolution is limited. Most estimates arise from analysis of global databases populated with unrelated sequences and is currently estimated at ∼27.7 substitutions/genome/year. SARS-CoV-2 polymerase contains a proofreading function encoded by NSP-14 limiting change. Additionally, virus evolution may be influenced by patient comorbidity. Intra-host mutational rate (MR) during infection remain poorly studied. Methods To minimize effect of vaccination and/or natural immunity on MR analysis, paired samples from adults originating from the initial pandemic wave (3/17/2020 through 5/27/2020) were retrieved and analyzed at Cleveland Clinic. Viral genome analysis was performed using next generation sequencing, and mutations between paired samples were quantified at allele frequencies (AF) ≥ 0.1, ≥ 0.5 and ≥ 0.75 and compared. MR was calculated employing F81 and JC69 evolution models and compared between isolates with (Δ NSP-14) and without (wildtype, wt) non-synonymous mutations in NSP-14 and by comorbidity. Results A total of 40 patients (80 sample pairs) were identified. Median interval between paired tests was 15 days [range 5-32]. The estimated MR by F81 modeling was 317.2 (95%CI 312.0-322.3), 54.6 (95%CI 52.5-56.7) and 45.1 (95%CI 43.1-47.0) substitutions/genome/year at AF of ≥0.1, ≥0.5, ≥0.75 respectively. Rates in ΔNSP-14 (n=13) vs wt (n=27) groups were 557.7 (95%CI 537.0-578.2) vs 193.1 (95%CI 187.1-199.1) p-value 0.001, 50.8 (95%CI 44.3-57.3) vs 56.3 (95%CI 53.1-59.4) p-value 0.144, and 31.0 (95%CI 25.9-36.1) vs 51.3 (95%CI 48.3-54.3) p- value < 0.001 at AF ≥0.1, ≥0.5, ≥0.75 respectively. Patients with immune comorbidities (n=6) had significantly higher MR of 137.6 (95%CI 114.6-160.5) vs 40.5 (95%CI 38.4-42.7) p-value < 0.001, and 113.7 (95%CI 92.8-134.5) vs 33.4 (95%CI 31.5-35.4) p-value < 0.001 at AF ≥0.5 and ≥0.75 respectively. Similar results were obtained when using the JC69 model. Conclusion Intra-host SARS-CoV-2 mutation rates are higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated MR at low AF. Immunosuppressed patients have elevated MR at higher AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling. Disclosures Frank Esper, M.D, Johnson and Johnson: Advisor/Consultant Daniel D. Rhoads, M.D. PhD, Luminex: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|Thermo Fisher: Advisor/Consultant.

Viral evolution

10.1093/ofid/ofac492.905

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782. Provider to Provider Electronic Consultation (E-consult): A Tool for the Pediatric Infectious Diseases Specialist to Document Encounters and Quantify Effort.

Open Forum Infectious Diseases (2019)

Blanca E. Gonzalez Charles B. Foster Frank Esper Heather L. Daniels Carla Saracusa

Abstract Background Curbside consultation is a ubiquitous practice within the medical field informally providing advice to community providers. The electronic consult (E-Consult) allows direct provider-to-provider communication between the primary care provider (PCP) and specialists using a secure electronic platform while documenting these interactions within the patient’s medical record (EMR). They offer PCP’s a forum for asking nonurgent questions. For the specialist, it allows review of the EMR, reduces medical liability of the curbside consult and provides a mechanism for generating RVUs. This service was implemented in our healthcare network (of over 300 pediatricians and pediatric specialists who see more than 500,000 pediatric visits each year) in April 2018. Our aim was to review and analyze the E-consults provided by the Pediatric Infectious Diseases (PID) service. Methods Cross-sectional study of E-consults performed by the PID from April 11 -2018-April 22 2019. Clinical queries were categorized by type and tabulated. Consult Billing was as following: Level 1=5 minutes (min); Level 2 =10min; Level 3= 15 minutes; Level 4= 25 minutes. RVU values were institutionally derived and assigned. Results We performed 171 E- consults with an average of 13 per month (range 3–18) generated from 59 providers (52 (88%) physicians and 7 (12%) certified nurse practitioners). Common reasons for the E-consult included: vaccine questions (25.7%), diagnosis questions (21.6%), exposure questions (20.4%) and treatment recommendations (10.5%). Of vaccine questions, 43% related to vaccine schedules /boosters, 13% vaccines for travel and 11.3% vaccines for the immunocompromised host. Consultation in the PID clinic was recommended for 25.7% patients, 9% requiring urgent evaluation. Of the 171 E-consults, 12.2% were evaluated in the PID clinic and 5% by another specialty. Billing was performed for 168 of the E consults= 9 level 1, 35 level 2, 83 level 3 and 41 level 4 generating 161 RVUs (equivalent to 53 level 4 new outpatient visits at our institution). Conclusion E-consults are an alternative to informal curbside consults for nonurgent clinical queries. Encounters are documented in the EMR and professional effort devoted to the task is tracked providing an additional source of RVU generation for the PID physician. Disclosures All authors: No reported disclosures.

Electronic medical record

Electronic health record

Medical record

10.1093/ofid/ofz360.850

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Serological Studies Confirm the Novel Astrovirus HMOAstV-C as a Highly Prevalent Human Infectious Agent

PLoS ONE (2011)

Peter D. Burbelo Kathryn H. Ching Frank Esper Michael J. Iadarola Eric Delwart

Molecular identification of a microbe is the first step in determining its prevalence of infection and pathogenic potential. Detection of specific adaptive immune responses can provide insights into whether a microbe is a human infectious agent and its epidemiology. Here we characterized human anti-IgG antibody responses by luciferase immunoprecipitation systems (LIPS) against two protein fragments derived from the capsid protein of the novel HMOAstV-C astrovirus. While antibodies to the N-terminal fragment were not informative, the C-terminal capsid fragment of HMOAstV-C showed a high frequency of immunoreactivity with serum from healthy blood donors. In contrast, a similar C-terminal capsid fragment from the related HMOAstV-A astrovirus failed to show immunoreactivity. Detailed analysis of adult serum from the United Sates using a standardized threshold demonstrated HMOAstV-C seropositivity in approximately 65% of the samples. Evaluation of serum samples from different pediatric age groups revealed that the prevalence of antibodies in 6–12 month, 1–2 year, 2–5 year and 5–10 year olds was 20%, 23%, 32% and 36%, respectively, indicating rising seroprevalence with age. Additionally, 50% (11/22) of the 0–6 month old children showed anti-HMOAstV-C antibody responses, likely reflecting maternal antibodies. Together these results document human humoral responses to HMOAstV-C and validate LIPS as a facile and effective approach for identifying humoral responses to novel infectious agents.

Seroprevalence

Astrovirus

Antibody Repertoire

10.1371/journal.pone.0022576

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Citations (70)

Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen

Open Forum Infectious Diseases (2017)

Anubhav Kanwar Suresh B. Selvaraju Frank Esper

Abstract Background Human Coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness, yet there are few recent studies characterizing disease among adults in the United States. Here, we describe CoV infections and clinical characteristics among adults (>18 years) presenting with respiratory illness in Cleveland, Ohio. Methods Between February 1, 2016 and April 30, 2017, 2949 nasopharyngeal swab specimens were analyzed by NxTAG Respiratory Pathogen Panel in adults presenting with respiratory illness at MetroHealth Medical Center. Clinical data were collected on adults whose samples screened positive for CoV-HKU1, CoV-OC43, CoV-229E or CoV-NL63. Results Coronaviruses were detected in 192 (6.5%) adults including 105 (3.5%) OC43, 67 (2.3%) 229E, 13 (0.4%) HKU1 and 7 (0.2%) NL63. The majority of adults with coronavirus infection were females (66.2%) with a median age of 53 years. Common comorbidities included smoking (40.0%), asthma (38.0%), COPD (35.4%), and inhaled corticosteroid use (28.6%). Eighty-five (46.4%) required admission to the hospital. Common presenting symptoms included shortness of breath (42.7%) and cough (31.0%) whereas fever was uncommon (12.5%). Gastrointestinal symptoms were more common in HKU1 and NL63 infected adults. Seventy-three percent of coronavirus disease occurred between the months of January and March. Despite the recognition of coronavirus infection, 70 (36.5%) received antibiotics for their disease. Conclusion This study provides needed insight into clinical characteristics and severity associated with coronavirus infection in adults. Coronavirus infection should be considered in differential diagnosis of respiratory tract illness in adults including those that require hospitalization, have a history of smoking and have pulmonary comorbidities. Disclosures All authors: No reported disclosures.

Coronavirus

Common cold

Respiratory tract

10.1093/ofid/ofx163.729

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Citations (1)

Evidence of human bocavirus circulating in children and adults, Cleveland, Ohio

Journal of Clinical Virology (2008)

Brian Chow Yung T. Huang Frank Esper

Human bocavirus

10.1016/j.jcv.2008.07.009

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