Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Acute cardiac events in hospitalized older adults with respiratory syncytial virus infection
Woodruff RC , Melgar M , Pham H , Sperling LS , Loustalot F , Kirley PD , Austin E , Yousey-Hindes K , Openo KP , Ryan P , Brown C , Lynfield R , Davis SS , Barney G , Tesini B , Sutton M , Talbot HK , Zahid H , Kim L , Havers FP . JAMA Intern Med 2024 IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection. OBJECTIVE: To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events. EXPOSURES: Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review. MAIN OUTCOMES AND MEASURES: Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events. RESULTS: The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31). CONCLUSIONS AND RELEVANCE: In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability. |
Characteristics and outcomes of pregnant women hospitalized with laboratory-confirmed respiratory syncytial virus before and during the COVID-19 pandemic
Milucky J , Patel K , Patton ME , Kirley PD , Austin E , Meek J , Anderson EJ , Brooks A , Brown C , Mumm E , Salazar-Sanchez Y , Barney G , Popham K , Sutton M , Talbot HK , Crossland MT , Havers FP . Open Forum Infect Dis 2024 11 (3) ofae042 BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease among infants and older adults. Less is known about RSV among pregnant women. METHODS: To analyze hospitalizations with laboratory-confirmed RSV among women aged 18 to 49 years, we used data from the RSV Hospitalization Surveillance Network (RSV-NET), a multistate population-based surveillance system. Specifically, we compared characteristics and outcomes among (1) pregnant and nonpregnant women during the pre-COVID-19 pandemic period (2014-2018), (2) pregnant women with respiratory symptoms during the prepandemic and pandemic periods (2021-2023), and (3) pregnant women with and without respiratory symptoms in the pandemic period. Using multivariable logistic regression, we examined whether pregnancy was a risk factor for severe outcomes (intensive care unit admission or in-hospital death) among women aged 18 to 49 years who were hospitalized with RSV prepandemic. RESULTS: Prepandemic, 387 women aged 18 to 49 years were hospitalized with RSV. Of those, 350 (90.4%) had respiratory symptoms, among whom 33 (9.4%) were pregnant. Five (15.2%) pregnant women and 74 (23.3%) nonpregnant women were admitted to the intensive care unit; no pregnant women and 5 (1.6%) nonpregnant women died. Among 279 hospitalized pregnant women, 41 were identified prepandemic and 238 during the pandemic: 80.5% and 35.3% had respiratory symptoms, respectively (P < .001). Pregnant women were more likely to deliver during their RSV-associated hospitalization during the pandemic vs the prepandemic period (73.1% vs 43.9%, P < .001). CONCLUSIONS: Few pregnant women had severe RSV disease, and pregnancy was not a risk factor for a severe outcome. More asymptomatic pregnant women were identified during the pandemic, likely due to changes in testing practices for RSV. |
Clinical outcomes of US adults hospitalized for COVID-19 and influenza in the Respiratory Virus Hospitalization Surveillance Network, October 2021-September 2022
Kojima N , Taylor CA , Tenforde MW , Ujamaa D , O'Halloran A , Patel K , Chai SJ , Daily Kirley P , Alden NB , Kawasaki B , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Reeg L , Tellez Nunez V , Lynfield R , Como-Sabetti K , Ropp SL , Shaw YP , Spina NL , Barney G , Bushey S , Popham K , Moran NE , Shiltz E , Sutton M , Abdullah N , Talbot HK , Schaffner W , Chatelain R , Price A , Garg S , Havers FP , Bozio CH . Open Forum Infect Dis 2024 11 (1) ofad702 Severe outcomes were common among adults hospitalized for COVID-19 or influenza, while the percentage of COVID-19 hospitalizations involving critical care decreased from October 2021 to September 2022. During the Omicron BA.5 period, intensive care unit admission frequency was similar for COVID-19 and influenza, although patients with COVID-19 had a higher frequency of in-hospital death. |
Delayed plasmodium falciparum malaria in pregnant patient with sickle cell trait 11 years after exposure, Oregon, USA
Drummond W , Rees K , Ladd-Wilson S , Mace KE , Blackall D , Sutton M . Emerg Infect Dis 2024 30 (1) 151-154 Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States. |
An antibody-free evaluation of an mRNA COVID-19 vaccine
Branham PJ , Cooper HC , Williamson YM , Najjar FN , Sutton WJH , Pierce-Ruiz CL , Barr JR , Williams TL . Biologicals 2023 85 101738 This manuscript describes the use of an analytical assay that combines transfection of mammalian cells and isotope dilution mass spectrometry (IDMS) for accurate quantification of antigen expression. Expired mRNA COVID-19 vaccine material was stored at 4 °C, room temperature (∼25 °C), and 56 °C over a period of 5 weeks. The same vaccine was also exposed to 5 freeze-thaw cycles. Every week, the spike protein antigenic expression in mammalian (BHK-21) cells was evaluated. Housekeeping proteins, β-actin and GAPDH, were simultaneously quantified to account for the variation in cell counts that occurs during maintenance and growth of cell cultures. Data show that vaccine stored at elevated temperatures results in reduced spike protein expression. Also, maintaining the vaccine in ultracold conditions or exposing the vaccine to freeze-thaw cycles had less effect on the vaccine's ability to produce the antigen in mammalian cells. We describe the use of IDMS as an antibody-free means to accurately quantify expressed protein from mammalian cells transfected with mRNA vaccine. |
High influenza incidence and disease severity among children and adolescents aged <18 years - United States, 2022-23 season
White EB , O'Halloran A , Sundaresan D , Gilmer M , Threlkel R , Colón A , Tastad K , Chai SJ , Alden NB , Yousey-Hindes K , Openo KP , Ryan PA , Kim S , Lynfield R , Spina N , Tesini BL , Martinez M , Schmidt Z , Sutton M , Talbot HK , Hill M , Biggerstaff M , Budd A , Garg S , Reed C , Iuliano AD , Bozio CH . MMWR Morb Mortal Wkly Rep 2023 72 (41) 1108-1114 During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October. |
Characteristics and outcomes among adults aged ≥60 years hospitalized with laboratory-confirmed respiratory syncytial virus - RSV-NET, 12 States, July 2022-June 2023
Havers FP , Whitaker M , Melgar M , Chatwani B , Chai SJ , Alden NB , Meek J , Openo KP , Ryan PA , Kim S , Lynfield R , Shaw YP , Barney G , Tesini BL , Sutton M , Talbot HK , Olsen KP , Patton ME . MMWR Morb Mortal Wkly Rep 2023 72 (40) 1075-1082 Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years. |
COVID-19-associated hospitalizations among U.S. Adults aged ≥65 years - COVID-NET, 13 States, January-August 2023
Taylor CA , Patel K , Patton ME , Reingold A , Kawasaki B , Meek J , Openo K , Ryan PA , Falkowski A , Bye E , Plymesser K , Spina N , Tesini BL , Moran NE , Sutton M , Talbot HK , George A , Havers FP . MMWR Morb Mortal Wkly Rep 2023 72 (40) 1089-1094 Adults aged ≥65 years remain at elevated risk for severe COVID-19 disease and have higher COVID-19-associated hospitalization rates compared with those in younger age groups. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to estimate COVID-19-associated hospitalization rates during January-August 2023 and identify demographic and clinical characteristics of hospitalized patients aged ≥65 years during January-June 2023. Among adults aged ≥65 years, hospitalization rates more than doubled, from 6.8 per 100,000 during the week ending July 15 to 16.4 per 100,000 during the week ending August 26, 2023. Across all age groups, adults aged ≥65 years accounted for 62.9% (95% CI = 60.1%-65.7%) of COVID-19-associated hospitalizations, 61.3% (95% CI = 54.7%-67.6%) of intensive care unit admissions, and 87.9% (95% CI = 80.5%-93.2%) of in-hospital deaths associated with COVID-19 hospitalizations. Most hospitalized adults aged ≥65 years (90.3%; 95% CI = 87.2%-92.8%) had multiple underlying conditions, and fewer than one quarter (23.5%; 95% CI = 19.5%-27.7%) had received the recommended COVID-19 bivalent vaccine. Because adults aged ≥65 years remain at increased risk for COVID-19-associated hospitalization and severe outcomes, guidance for this age group should continue to focus on measures to prevent SARS-CoV-2 infection, encourage vaccination, and promote early treatment for persons who receive a positive SARS-CoV-2 test result to reduce their risk for severe COVID-19-associated outcomes. |
Clinical Trends Among U.S. Adults Hospitalized with COVID-19, March-December 2020 (preprint)
Garg S , Patel K , Pham H , Whitaker M , O'Halloran A , Milucky J , Anglin O , Kirley PD , Reingold A , Kawasaki B , Herlihy R , Yousey-Hindes K , Maslar A , Anderson EJ , Openo KP , Weigel A , Teno K , Ryan PA , Monroe ML , Reeg L , Kim S , Como-Sabetti K , Bye E , Shrum Davis S , Eisenberg N , Muse A , Barney G , Bennett NM , Felsen CB , Billing L , Shiltz J , Sutton M , Abdullah N , Talbot HK , Schaffner W , Hill M , Chatelain R , Wortham J , Taylor C , Hall A , Fry AM , Kim L , Havers FP . medRxiv 2021 2021.04.21.21255473 Background The COVID-19 pandemic has caused substantial morbidity and mortality.Objectives To describe monthly demographic and clinical trends among adults hospitalized with COVID-19.Design Pooled cross-sectional.Setting 99 counties within 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).Patients U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-December 31, 2020.Measurements Monthly trends in weighted percentages of interventions and outcomes including length of stay (LOS), intensive care unit admissions (ICU), invasive mechanical ventilation (IMV), vasopressor use and in-hospital death (death). Monthly hospitalization, ICU and death rates per 100,000 population.Results Among 116,743 hospitalized adults, median age was 62 years. Among 18,508 sampled adults, median LOS decreased from 6.4 (March) to 4.6 days (December). Remdesivir and systemic corticosteroid use increased from 1.7% and 18.9% (March) to 53.8% and 74.2% (December), respectively. Frequency of ICU decreased from 37.8% (March) to 20.5% (December). IMV (27.8% to 8.7%), vasopressors (22.7% to 8.8%) and deaths (13.9% to 8.7%) decreased from March to October; however, percentages of these interventions and outcomes remained stable or increased in November and December. Percentage of deaths significantly decreased over time for non-Hispanic White patients (p-value <0.01) but not non-Hispanic Black or Hispanic patients. Rates of hospitalization (105.3 per 100,000), ICU (20.2) and death (11.7) were highest during December.Limitations COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.Conclusions After initial improvement during April-October 2020, trends in interventions and outcomes worsened during November-December, corresponding with the 3rd peak of the U.S. pandemic. These data provide a longitudinal assessment of trends in COVID-19-associated outcomes prior to widespread COVID-19 vaccine implementation.Competing Interest StatementDr. Evan Anderson reports grants from Pfizer, grants from Merck, grants from PaxVax, grants from Micron, grants from Sanofi-Pasteur, grants from Janssen, grants from MedImmune, grants from GSK, personal fees from Sanofi-Pasteur, personal fees from Pfizer, personal fees from Medscape, personal fees from Kentucky Bioprocessing, Inc, personal fees from Sanofi-Pasteur, outside the submitted work. Dr. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. Sites participating in COVID-NET obtained approval from their respective state and local Institutional Review Boards, as applicable.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting check ist(s) and other pertinent material as supplementary files, if applicable.YesPublicly available data referred to in this analysis can be found at: https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/covidnet/covid19_3.html |
COVID-19-associated hospitalizations among vaccinated and unvaccinated adults ≥18 years – COVID-NET, 13 states, January 1 – July 24, 2021 (preprint)
Havers FP , Pham H , Taylor CA , Whitaker M , Patel K , Anglin O , Kambhampati AK , Milucky J , Zell E , Chai SJ , Kirley PD , Alden NB , Armistead I , Yousey-Hindes K , Meek J , Openo KP , Anderson EJ , Reeg L , Kohrman A , Lynfield R , Como-Sabetti K , Davis EM , Cline C , Muse A , Barney G , Bushey S , Felsen CB , Billing LM , Shiltz E , Sutton M , Abdullah N , Talbot HK , Schaffner W , Hill M , George A , Murthy BP , McMorrow M . medRxiv 2021 2021.08.27.21262356 Background As of August 21, 2021, >60% of the U.S. population aged ≥18 years were fully vaccinated with vaccines highly effective in preventing hospitalization due to Coronavirus Disease-2019 (COVID-19). Infection despite full vaccination (vaccine breakthrough) has been reported, but characteristics of those with vaccine breakthrough resulting in hospitalization and relative rates of hospitalization in unvaccinated and vaccinated persons are not well described, including during late June and July 2021 when the highly transmissible Delta variant predominated.Methods From January 1–June 30, 2021, cases defined as adults aged ≥18 years with laboratory-confirmed Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection were identified from >250 acute care hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network (COVID-NET). Through chart review for sampled cases, we examine characteristics associated with vaccination breakthrough. From January 24–July 24, 2021, state immunization information system data linked to both >37,000 cases representative cases and the defined surveillance catchment area population were used to compare weekly hospitalization rates in vaccinated and unvaccinated individuals. Unweighted case counts and weighted percentages are presented.Results From January 1 – June 30, 2021, fully vaccinated cases increased from 1 (0.01%) to 321 (16.1%) per month. Among 4,732 sampled cases, fully vaccinated persons admitted with COVID-19 were older compared with unvaccinated persons (median age 73 years [Interquartile Range (IQR) 65-80] v. 59 years [IQR 48-70]; p<0.001), more likely to have 3 or more underlying medical conditions (201 (70.8%) v. 2,305 (56.1%), respectively; p<0.001) and be residents of long-term care facilities [37 (14.5%) v. 146 (5.5%), respectively; p<0.001]. From January 24 – July 24, 2021, cumulative hospitalization rates were 17 times higher in unvaccinated persons compared with vaccinated persons (423 cases per 100,000 population v. 26 per 100,000 population, respectively); rate ratios were 23, 22 and 13 for those aged 18-49, 50-64, and ≥65 years respectively. For June 27 – July 24, hospitalization rates were ≥10 times higher in unvaccinated persons compared with vaccinated persons for all age groups across all weeks.Conclusion Population-based hospitalization rates show that unvaccinated adults aged ≥18 years are 17 times more likely to be hospitalized compared with vaccinated adults. Rates are far higher in unvaccinated persons in all adult age groups, including during a period when the Delta variant was the predominant strain of the SARS-CoV-2 virus. Vaccines continue to play a critical role in preventing serious COVID-19 illness and remain highly effective in preventing COVID-19 hospitalizations.Competing Interest StatementAll authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Evan J. Anderson reports grants from Pfizer, grants from Merck, grants from PaxVax, grants from Micron, grants from Sanofi-Pasteur, grants from Janssen, grants from MedImmune, grants from GSK, personal fees from Sanofi-Pasteur, personal fees from Pfizer, personal fees from Medscape, personal fees from Kentucky Bioprocessing, Inc, personal fees from Sanofi-Pasteur, personal fees from Janssen, outside the submitted work; and his institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Ruth Lynfield reports Associate Editor for American Academy of Pediatrics Red Book (Committee on Infectious Diseases), donated fee to Minnesota Department of Health. Laurie M. Billing reports grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study; grants from Centers for Disease Control and Prevention (CDC) outside the submitted work. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. No other potential conflicts of interest were disclosed.Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (see e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesPublicly available data referred to in this analysis can be found at: https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html |
Risk Factors for COVID-19-associated hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System (preprint)
Ko JY , Danielson ML , Town M , Derado G , Greenlund KJ , Daily Kirley P , Alden NB , Yousey-Hindes K , Anderson EJ , Ryan PA , Kim S , Lynfield R , Torres SM , Barney GR , Bennett NM , Sutton M , Talbot HK , Hill M , Hall AJ , Fry AM , Garg S , Kim L . medRxiv 2020 2020.07.27.20161810 Background Identification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care.Objective To examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations.Design Cross-sectional.Setting 70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System.Participants U.S. community-dwelling adults (≥18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020.Measurements Adjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m2], severe obesity [BMI≥40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease).Results Our sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults ≥65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites).Limitations Interim analysis limited to hospitalizations with underlying medical condition data.Conclusion Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.Competing Interest StatementDr. Anderson reports personal fees from AbbVie, personal fees from Pfizer, grants from Pfizer, grants from Merck, grants from Micron, grants from Paxvax, grants from Sanofi Pasteur, grants from Novavax, grants from MedImmune, grants from Regeneron, grants from GSK, outside the submitted work. Mr. Henderson, Ms. Kim, Ms. George, and Ms. Hill report grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study. Dr. Lynfield reports grants from CDC- Emerging Infections Program, during the conduct of the study; and Royalties from a book on infectious disease surveillance and compensation for AAP Red Book (Report from Committee on Infectious Disease) donated to Minnesota Dept of Health. Dr. Schaffner reports grants from CDC, during the conduct of the study; personal fees from VBI Vaccines, outside the submitted work. Dr. Talbot reports other from Seqirus, outside the submitted work.Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This analysis was exempt from CDC's Institutional Review Board, as it was considered part of public health surveillance and emergency response. Participating sites obtained approval for the COVID-NET surveillance protocol from their respective state and local IRBs, as required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved regi try, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData is not publically available at this time. |
Interim Analysis of Risk Factors for Severe Outcomes among a Cohort of Hospitalized Adults Identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) (preprint)
Kim L , Garg S , O'Halloran A , Whitaker M , Pham H , Anderson EJ , Armistead I , Bennett NM , Billing L , Como-Sabetti K , Hill M , Kim S , Monroe ML , Muse A , Reingold AL , Schaffner W , Sutton M , Talbot HK , Torres SM , Yousey-Hindes K , Holstein R , Cummings C , Brammer L , Hall AJ , Fry AM , Langley GE . medRxiv 2020 2020.05.18.20103390 Background As of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally.Objective To describe risk factors for severe outcomes among adults hospitalized with COVID-19.Design Cohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network.Setting 154 acute care hospitals in 74 counties in 13 states.Patients 2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020.Measurements Age, sex, race/ethnicity, and underlying medical conditions.Results Ninety-two percent of patients had ≥1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death.Limitation Data were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded.Conclusion In-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies.Funding Source This work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Competing Interest StatementH. Keipp Talbot reports personal fees from Seqirus outside the submitted work. William Schaffner reports personal fees from Pfizer and personal fees from Roche Diagnostics outside the submitted work. Evan Anderson reports personal fees from Abbvie and Pfizer outside the submitted work. H. Keipp Talbot reports grants from Sanofi outside the submitted work; Mary Hill reports grants from CSTE, during the conduct of the study; Melissa Sutton reports grants from CDC Emerging Infections Program during the conduct of the study; William Schaffner reports grants from CDC during the conduct of the study. Sue Kim reports grants from CSTE during the conduct of the study. Evan Anderson reports grants from Pfizer, grants from MedImmune, grants from Regeneron, grants from PaxVax, grants from Merck, grants from Novavax, grants from Sanofi-Pasteur, grants from Micron, outside the submitted work. Laurie Billing reports grants from the Council of State and Territorial Epidemiologists (CSTE) and the Centers for Disease Control and Prevention (CDC) during the conduct of the study.Funding StatementThis work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that al clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAggregate data is available on CDC’s COVID-NET Interactive website. https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html |
Robustness of the ferret model for influenza risk assessment studies: a cross-laboratory exercise (preprint)
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . bioRxiv 2022 2022.04.02.486825 Ferrets represent the preferred animal model for assessing the transmission potential of newly emerged zoonotic influenza viruses. However, heterogeneity among established experimental protocols and facilities across different laboratories may lead to variable results, complicating interpretation of transmission experimental data. Between 2018-2020, a global exercise was conducted by 11 participating laboratories to assess the range of variation in ferret transmission experiments using two common stock H1N1 influenza viruses that possess different transmission characteristics in ferrets. Inoculation route, dose, and volume were standardized, and all participating laboratories followed the same experimental conditions for respiratory droplet transmission, including a strict 1:1 donor:contact ratio. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored throughout. Overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. To attain high confidence in identifying zoonotic influenza viruses with moderate-to-high or low transmissibility, our analyses support that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.Competing Interest StatementThe authors have declared no competing interest. |
Trends in laboratory-confirmed SARS-CoV-2 reinfections and associated hospitalizations and deaths among adults aged 18 years - 18 U.S. Jurisdictions, September 2021-December 2022
Ma KC , Dorabawila V , León TM , Henry H , Johnson AG , Rosenberg E , Mansfield JA , Midgley CM , Plumb ID , Aiken J , Khanani QA , Auche S , Bayoumi NS , Bennett SA , Bernu C , Chang C , Como-Sabetti KJ , Cueto K , Cunningham S , Eddy M , Falender RA , Fleischauer A , Frank DM , Harrington P , Hoskins M , Howsare A , Ingaiza LM , Islam AS , Jensen SA , Jones JM , Kambach G , Kanishka F , Levin Y , Masarik JF 3rd , Meyer SD , Milroy L , Morris KJ , Olmstead J , Olsen NS , Omoike E , Patel K , Pettinger A , Pike MA , Reed IG , Slocum E , Sutton M , Tilakaratne BP , Vest H , Vostok J , Wang JS , Watson-Lewis L , Wienkes HN , Hagen MB , Silk BJ , Scobie HM . MMWR Morb Mortal Wkly Rep 2023 72 (25) 683-689 Although reinfections with SARS-CoV-2 have occurred in the United States with increasing frequency, U.S. epidemiologic trends in reinfections and associated severe outcomes have not been characterized. Weekly counts of SARS-CoV-2 reinfections, total infections, and associated hospitalizations and deaths reported by 18 U.S. jurisdictions during September 5, 2021-December 31, 2022, were analyzed overall, by age group, and by five periods of SARS-CoV-2 variant predominance (Delta and Omicron [BA.1, BA.2, BA.4/BA.5, and BQ.1/BQ.1.1]). Among reported reinfections, weekly trends in the median intervals between infections and frequencies of predominant variants during previous infections were calculated. As a percentage of all infections, reinfections increased substantially from the Delta (2.7%) to the Omicron BQ.1/BQ.1.1 (28.8%) periods; during the same periods, increases in the percentages of reinfections among COVID-19-associated hospitalizations (from 1.9% [Delta] to 17.0% [Omicron BQ.1/BQ.1.1]) and deaths (from 1.2% [Delta] to 12.3% [Omicron BQ.1/BQ.1.1]) were also substantial. Percentages of all COVID-19 cases, hospitalizations, and deaths that were reinfections were consistently higher across variant periods among adults aged 18-49 years compared with those among adults aged ≥50 years. The median interval between infections ranged from 269 to 411 days by week, with a steep decline at the start of the BA.4/BA.5 period, when >50% of reinfections occurred among persons previously infected during the Alpha variant period or later. To prevent severe COVID-19 outcomes, including those following reinfection, CDC recommends staying up to date with COVID-19 vaccination and receiving timely antiviral treatments, when eligible. |
Estimated effectiveness of JYNNEOS vaccine in preventing Mpox: A Multijurisdictional Case-Control Study - United States, August 19, 2022-March 31, 2023
Dalton AF , Diallo AO , Chard AN , Moulia DL , Deputy NP , Fothergill A , Kracalik I , Wegner CW , Markus TM , Pathela P , Still WL , Hawkins S , Mangla AT , Ravi N , Licherdell E , Britton A , Lynfield R , Sutton M , Hansen AP , Betancourt GS , Rowlands JV , Chai SJ , Fisher R , Danza P , Farley M , Zipprich J , Prahl G , Wendel KA , Niccolai L , Castilho JL , Payne DC , Cohn AC , Feldstein LR . MMWR Morb Mortal Wkly Rep 2023 72 (20) 553-558 As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,(†) including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,(§) to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),(¶) regardless of administration route or immunocompromise status. |
Quantification of SARS-CoV-2 spike protein expression from mRNA vaccines using isotope dilution mass spectrometry
Sutton WJH , Branham PJ , Williamson YM , Cooper HC , Najjar FN , Pierce-Ruiz CL , Barr JR , Williams TL . Vaccine 2023 The advent of mRNA vaccine technology has been vital in rapidly creating and manufacturing COVID-19 vaccines at an industrial scale. To continue to accelerate this leading vaccine technology, an accurate method is needed to quantify antigens produced by the transfection of cells with a mRNA vaccine product. This will allow monitoring of protein expression during mRNA vaccine development and provide information on how changes to vaccine components affects the expression of the desired antigen. Developing novel approaches that allow for high-throughput screening of vaccines to detect changes in antigen production in cell culture prior to in vivo studies could aid vaccine development. We have developed and optimized an isotope dilution mass spectrometry method to detect and quantify the spike protein expressed after transfection of baby hamster kidney cells with expired COVID-19 mRNA vaccines. Five peptides of the spike protein are simultaneously quantified and provide assurance that protein digestion in the region of the target peptides is complete since results between the five peptides had a relative standard deviation of less than 15 %. In addition, two housekeeping proteins, actin and GAPDH, are quantified in the same analytical run to account for any variation in cell growth within the experiment. IDMS allows a precise and accurate means to quantify protein expression by mammalian cells transfected with an mRNA vaccine. |
COVID-19 surveillance after expiration of the public health emergency declaration - United States, May 11, 2023
Silk BJ , Scobie HM , Duck WM , Palmer T , Ahmad FB , Binder AM , Cisewski JA , Kroop S , Soetebier K , Park M , Kite-Powell A , Cool A , Connelly E , Dietz S , Kirby AE , Hartnett K , Johnston J , Khan D , Stokley S , Paden CR , Sheppard M , Sutton P , Razzaghi H , Anderson RN , Thornburg N , Meyer S , Womack C , Weakland AP , McMorrow M , Broeker LR , Winn A , Hall AJ , Jackson B , Mahon BE , Ritchey MD . MMWR Morb Mortal Wkly Rep 2023 72 (19) 523-528 On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4). |
Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021.
Taylor CA , Patel K , Pham H , Whitaker M , Anglin O , Kambhampati AK , Milucky J , Chai SJ , Kirley PD , Alden NB , Armistead I , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Teno K , Weigel A , Monroe ML , Ryan PA , Henderson J , Nunez VT , Bye E , Lynfield R , Poblete M , Smelser C , Barney GR , Spina NL , Bennett NM , Popham K , Billing LM , Shiltz E , Abdullah N , Sutton M , Schaffner W , Talbot HK , Ortega J , Price A , Garg S , Havers FP , COVID-NET Surveillance Team . MMWR Morb Mortal Wkly Rep 2021 70 (43) 1513-1519 In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults. |
Laboratory-Confirmed COVID-19-Associated Hospitalizations Among Adults During SARS-CoV-2 Omicron BA.2 Variant Predominance - COVID-19-Associated Hospitalization Surveillance Network, 14 States, June 20, 2021-May 31, 2022.
Havers FP , Patel K , Whitaker M , Milucky J , Reingold A , Armistead I , Meek J , Anderson EJ , Weigel A , Reeg L , Seys S , Ropp SL , Spina N , Felsen CB , Moran NE , Sutton M , Talbot HK , George A , Taylor CA , COVID-NET Surveillance Team . MMWR Morb Mortal Wkly Rep 2022 71 (34) 1085-1091 Beginning the week of March 20–26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19–associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20–May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18–49 and 50–64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1). Beginning the week of March 20–26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19–associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20–May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18–49 and 50–64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1). |
Vaccination status and trends in adult COVID-19-associated hospitalizations by race and ethnicity, March 2020-August 2022
Ko JY , Pham H , Anglin O , Chai SJ , Alden NB , Meek J , Anderson EJ , Weigel A , Kohrman A , Lynfield R , Rudin D , Barney G , Bennett NM , Billing LM , Sutton M , Talbot HK , Swain A , Havers FP , Taylor CA . Clin Infect Dis 2023 77 (6) 827-838 BACKGROUND: We sought to evaluate whether race/ethnicity disparities in severe COVID-19 outcomes persist in the era of vaccination. METHODS: Population-based age-adjusted monthly rate ratios (RR) of laboratory-confirmed COVID-19-asssociated hospitalizations were calculated among adult patients from COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) during March 2020 - August 2022, by race/ethnicity. Among randomly sampled patients, July 2021-August 2022, RRs for hospitalization, intensive care unit (ICU) admission, and in-hospital mortality were calculated for Hispanic, Black, American Indian/Alaskan Native (AI/AN), and Asian/Pacific Islander (API) versus White persons. RESULTS: Based on data from 353,807 hospitalized patients, hospitalization rates were higher among Hispanic, Black and AI/AN versus White persons during March 2020 - August 2022, yet the magnitude of the disparities declined over time (for Hispanic, RR=6.7; 95%CI: 6.5-7.1 in June 2020 vs RR<2.0 after July 2021; for AI/AN, RR=8.4; 95%CI: 8.2-8.7in May 2020 vs RR<2.0 after March 2022; and for Black persons RR=5.3; 95%CI: 4.6-4.9 in July 2020 vs RR<2.0 after February 2022; all p≤0.001). Among 8,706 sampled patients during July 2021 - August 2022, hospitalization and ICU admission RRs were higher for Hispanic, Black, and AI/AN (range for both hospitalization and ICU admission: 1.4-2.4) and lower for API (range for both: 0.6-0.9) versus White persons. All other race and ethnicity groups had higher in-hospital mortality rates versus White persons (RR range: 1.4-2.9). CONCLUSIONS: Race/ethnicity disparities in COVID-19-associated hospitalizations declined but persist in the era of vaccination. Developing strategies to ensure equitable access to vaccination and treatment remains important. |
Codetections of other respiratory viruses among children hospitalized with COVID-19
Agathis NT , Patel K , Milucky J , Taylor CA , Whitaker M , Pham H , Anglin O , Chai SJ , Alden NB , Meek J , Anderson EJ , Weigel A , Kim S , Lynfield R , Smelser C , Muse A , Popham K , Billing LM , Sutton M , Talbot HK , George A , McMorrow M , Havers FP . Pediatrics 2023 151 (2) OBJECTIVES: To assess the clinical impact of respiratory virus codetections among children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: During March 2020 to February 2022, the US coronavirus disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) identified 4372 children hospitalized with SARS-CoV-2 infection admitted primarily for fever, respiratory illness, or presumed COVID-19. We compared demographics, clinical features, and outcomes between those with and without codetections who had any non-SARS-CoV-2 virus testing. Among a subgroup of 1670 children with complete additional viral testing, we described the association between presence of codetections and severe respiratory illness using age-stratified multivariable logistic regression models. RESULTS: Among 4372 children hospitalized, 62% had non-SARS-CoV-2 respiratory virus testing, of which 21% had a codetection. Children with codetections were more likely to be <5 years old (yo), receive increased oxygen support, or be admitted to the ICU (P < .001). Among children <5 yo, having any viral codetection (<2 yo: adjusted odds ratio [aOR] 2.1 [95% confidence interval [CI] 1.5-3.0]; 2-4 yo: aOR 1.9 [95% CI 1.2-3.1]) or rhinovirus/enterovirus codetection (<2 yo: aOR 2.4 [95% CI 1.6-3.7]; 2-4: aOR 2.4 [95% CI 1.2-4.6]) was significantly associated with severe illness. Among children <2 yo, respiratory syncytial virus (RSV) codetections were also significantly associated with severe illness (aOR 1.9 [95% CI 1.3-2.9]). No significant associations were seen among children ≥5 yo. CONCLUSIONS: Respiratory virus codetections, including RSV and rhinovirus/enterovirus, may increase illness severity among children <5 yo hospitalized with SARS-CoV-2 infection. |
Bacterial and viral infections among adults hospitalized with COVID-19, COVID-NET, 14 states, March 2020-April 2022
Shah MM , Patel K , Milucky J , Taylor CA , Reingold A , Armistead I , Meek J , Anderson EJ , Weigel A , Reeg L , Como-Sabetti K , Ropp SL , Muse A , Bushey S , Shiltz E , Sutton M , Talbot HK , Chatelain R , Havers FP . Influenza Other Respir Viruses 2023 17 (3) e13107 BACKGROUND: Bacterial and viral infections can occur with SARS-CoV-2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. METHODS: We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection between March 2020 and April 2022. Clinician-driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. We also describe the prevalence of viral pathogens including respiratory syncytial virus, rhinovirus/enterovirus, influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and non-SARS-CoV-2 endemic coronaviruses. RESULTS: Among 36 490 hospitalized adults with COVID-19, 53.3% had bacterial cultures taken within 7 days of admission and 6.0% of these had a clinically relevant bacterial pathogen. After adjustment for demographic factors and co-morbidities, bacterial infections in patients with COVID-19 within 7 days of admission were associated with an adjusted relative risk of death 2.3 times that of patients with negative bacterial testing. Staphylococcus aureus and Gram-negative rods were the most frequently isolated bacterial pathogens. Among hospitalized adults with COVID-19, 2766 (7.6%) were tested for seven virus groups. A non-SARS-CoV-2 virus was identified in 0.9% of tested patients. CONCLUSIONS: Among patients with clinician-driven testing, 6.0% of adults hospitalized with COVID-19 were identified to have bacterial coinfections and 0.9% were identified to have viral coinfections; identification of a bacterial coinfection within 7 days of admission was associated with increased mortality. |
Acute cardiac events during COVID-19-associated hospitalizations
Woodruff RC , Garg S , George MG , Patel K , Jackson SL , Loustalot F , Wortham JM , Taylor CA , Whitaker M , Reingold A , Alden NB , Meek J , Anderson EJ , Weigel A , Henderson J , Bye E , Davis SS , Barney G , Bennett NM , Shiltz E , Sutton M , Talbot HK , Price A , Sperling LS , Havers FP . J Am Coll Cardiol 2023 81 (6) 557-569 BACKGROUND: COVID-19 is associated with cardiac complications. OBJECTIVES: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. METHODS: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. RESULTS: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. CONCLUSIONS: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization. |
Influenza antiviral use in patients hospitalized with laboratory-confirmed influenza in the United States, FluSurv-NET, 2015-2019
Tenforde MW , Cummings CN , O'Halloran AC , Rothrock G , Kirley PD , Alden NB , Meek J , Yousey-Hindes K , Openo KP , Anderson EJ , Monroe ML , Kim S , Nunez VT , McMahon M , McMullen C , Khanlian SA , Spina NL , Muse A , Gaitán MA , Felsen CB , Lung K , Shiltz E , Sutton M , Thomas A , Talbot HK , Schaffner W , Price A , Chatelain R , Reed C , Garg S . Open Forum Infect Dis 2023 10 (1) ofac681 From surveillance data of patients hospitalized with laboratory-confirmed influenza in the United States during the 2015-2016 through 2018-2019 seasons, initiation of antiviral treatment increased from 86% to 94%, with increases seen across all age groups. However, 62% started therapy ≥3 days after illness onset, driven by late presentation to care. |
Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.
Bonner KE , Sukerman E , Liko J , Lanzieri TM , Sutton M , DeBess E , Leesman C , Icenogle J , Hao L , Chen MH , Faisthalab R , Leman RF , Cieslak PR , DeRavin SS , Perelygina L . Front Immunol 2022 13 1075351 A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts. |
Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza - United States, 2021-22 Influenza Season.
Adams K , Tastad KJ , Huang S , Ujamaa D , Kniss K , Cummings C , Reingold A , Roland J , Austin E , Kawasaki B , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Reeg L , Leegwater L , McMahon M , Bye E , Poblete M , Landis Z , Spina NL , Engesser K , Bennett NM , Gaitan MA , Shiltz E , Moran N , Sutton M , Abdullah N , Schaffner W , Talbot HK , Olsen K , Staten H , Taylor CA , Havers FP , Reed C , Budd A , Garg S , O'Halloran A , Brammer L . MMWR Morb Mortal Wkly Rep 2022 71 (50) 1589-1596 The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),(§) and notifiable pediatric deaths associated(¶) with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.(††) To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months. |
Excess all-cause mortality in the USA and Europe during the COVID-19 pandemic, 2020 and 2021.
Rossen LM , Nørgaard SK , Sutton PD , Krause TG , Ahmad FB , Vestergaard LS , Mølbak K , Anderson RN , Nielsen J . Sci Rep 2022 12 (1) 18559 Both the USA and Europe experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This retrospective observational study included data on deaths from all causes occurring in the USA and 25 European countries or subnational areas participating in the network for European monitoring of excess mortality for public health action (EuroMOMO). We applied the EuroMOMO algorithm to estimate excess all-cause mortality in the USA and Europe during the first two years of the COVID-19 pandemic, 2020-2021, and compared excess mortality by age group and time periods reflecting three primary waves. During 2020-2021, the USA experienced 154.5 (95% Uncertainty Interval [UI]: 154.2-154.9) cumulative age-standardized excess all-cause deaths per 100,000 person years, compared with 110.4 (95% UI: 109.9-111.0) for the European countries. Excess all-cause mortality in the USA was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020-2021. If the USA had experienced an excess mortality rate similar to Europe, there would have been approximately 391 thousand (36%) fewer excess deaths in the USA. |
COVID-19-Associated Hospitalizations Among U.S. Infants Aged <6 Months - COVID-NET, 13 States, June 2021-August 2022.
Hamid Sarah, Woodworth Kate, Pham Huong, Milucky Jennifer, Chai Shua J, Kawasaki Breanna, Yousey-Hindes Kimberly, Anderson Evan J, Henderson Justin, Lynfield Ruth, Pacheco Francesca, Barney Grant, Bennett Nancy M, Shiltz Eli, Sutton Melissa, Talbot H Keipp, Price Andrea, Havers Fiona P, Taylor Christopher A, . MMWR. Morbidity and mortality weekly report 2022 71(45) 1442-1448 . MMWR. Morbidity and mortality weekly report 2022 71(45) 1442-1448 Hamid Sarah, Woodworth Kate, Pham Huong, Milucky Jennifer, Chai Shua J, Kawasaki Breanna, Yousey-Hindes Kimberly, Anderson Evan J, Henderson Justin, Lynfield Ruth, Pacheco Francesca, Barney Grant, Bennett Nancy M, Shiltz Eli, Sutton Melissa, Talbot H Keipp, Price Andrea, Havers Fiona P, Taylor Christopher A, . MMWR. Morbidity and mortality weekly report 2022 71(45) 1442-1448 |
COVID-19-Associated Hospitalizations Among Vaccinated and Unvaccinated Adults 18 Years or Older in 13 US States, January 2021 to April 2022.
Havers FP , Pham H , Taylor CA , Whitaker M , Patel K , Anglin O , Kambhampati AK , Milucky J , Zell E , Moline HL , Chai SJ , Kirley PD , Alden NB , Armistead I , Yousey-Hindes K , Meek J , Openo KP , Anderson EJ , Reeg L , Kohrman A , Lynfield R , Como-Sabetti K , Davis EM , Cline C , Muse A , Barney G , Bushey S , Felsen CB , Billing LM , Shiltz E , Sutton M , Abdullah N , Talbot HK , Schaffner W , Hill M , George A , Hall AJ , Bialek SR , Murthy NC , Murthy BP , McMorrow M . JAMA Intern Med 2022 182 (10) 1071-1081 IMPORTANCE: Understanding risk factors for hospitalization in vaccinated persons and the association of COVID-19 vaccines with hospitalization rates is critical for public health efforts to control COVID-19. OBJECTIVE: To determine characteristics of COVID-19-associated hospitalizations among vaccinated persons and comparative hospitalization rates in unvaccinated and vaccinated persons. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2021, to April 30, 2022, patients 18 years or older with laboratory-confirmed SARS-CoV-2 infection were identified from more than 250 hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network. State immunization information system data were linked to cases, and the vaccination coverage data of the defined catchment population were used to compare hospitalization rates in unvaccinated and vaccinated individuals. Vaccinated and unvaccinated patient characteristics were compared in a representative sample with detailed medical record review; unweighted case counts and weighted percentages were calculated. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: COVID-19-associated hospitalization rates among vaccinated vs unvaccinated persons and factors associated with COVID-19-associated hospitalization in vaccinated persons were assessed. RESULTS: Using representative data from 19509 hospitalizations (see Table 1 for demographic information), monthly COVID-19-associated hospitalization rates ranged from 3.5 times to 17.7 times higher in unvaccinated persons than vaccinated persons regardless of booster dose status. From January to April 2022, when the Omicron variant was predominant, hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Among sampled cases, vaccinated hospitalized patients with COVID-19 were older than those who were unvaccinated (median [IQR] age, 70 [58-80] years vs 58 [46-70] years, respectively; P<.001) and more likely to have 3 or more underlying medical conditions (1926 [77.8%] vs 4124 [51.6%], respectively; P<.001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults hospitalized with COVID-19, unvaccinated adults were more likely to be hospitalized compared with vaccinated adults; hospitalization rates were lowest in those who had received a booster dose. Hospitalized vaccinated persons were older and more likely to have 3 or more underlying medical conditions and be long-term care facility residents compared with hospitalized unvaccinated persons. The study results suggest that clinicians and public health practitioners should continue to promote vaccination with all recommended doses for eligible persons. |
Robustness of the ferret model for influenza risk assessment studies: A cross-laboratory exercise
Belser JA , Lau EHY , Barclay W , Barr IG , Chen H , Fouchier RAM , Hatta M , Herfst S , Kawaoka Y , Lakdawala SS , Lee LYY , Neumann G , Peiris M , Perez DR , Russell C , Subbarao K , Sutton TC , Webby RJ , Yang H , Yen HL . mBio 2022 13 (4) e0117422 Past pandemic influenza viruses with sustained human-to-human transmissibility have emerged from animal influenza viruses. Employment of experimental models to assess the pandemic risk of emerging zoonotic influenza viruses provides critical information supporting public health efforts. Ferret transmission experiments have been utilized to predict the human-to-human transmission potential of novel influenza viruses. However, small sample sizes and a lack of standardized protocols can introduce interlaboratory variability, complicating interpretation of transmission experimental data. To assess the range of variation in ferret transmission experiments, a global exercise was conducted by 11 laboratories using two common stock H1N1 influenza viruses with different transmission characteristics in ferrets. Parameters known to affect transmission were standardized, including the inoculation route, dose, and volume, as well as a strict 1:1 donor/contact ratio for respiratory droplet transmission. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored and analyzed. The overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. Among environmental parameters that varied across laboratories, donor-to-contact airflow directionality was associated with increased transmissibility. To attain high confidence in identifying viruses with moderate to high transmissibility or low transmissibility under a smaller number of participating laboratories, our analyses support the notion that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment. IMPORTANCE Following detection of a novel virus, rapid characterization efforts (both in vitro and in vivo) are undertaken at numerous laboratories worldwide to evaluate the relative risk posed to human health. Aggregation of these data are critical, but the use of nonstandardized protocols can make interpretation of divergent results a challenge. For evaluation of virus transmissibility, a multifactorial trait which can only be evaluated in vivo, identifying intrinsic levels of variability between groups can improve the utility of these data, as well as ensure that experiments are performed with sufficient replication to ensure high confidence in compiled results. Using the ferret transmission model and two influenza A viruses, we conducted a multicenter standardization exercise to improve the interpretation of transmission data generated during risk assessment activities; this exercise serves as a model for future efforts employing both in vitro and in vivo models against possible pandemic pathogens. |
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