Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 74 Records) |
Query Trace: Kobayashi M[original query] |
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Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of End Stage Kidney Disease in Diabetes.
Satake E , Saulnier PJ , Kobayashi H , Gupta MK , Looker HC , Wilson JM , Md Dom ZI , Ihara K , O'Neil K , Krolewski B , Pipino C , Pavkov ME , Nair V , Bitzer M , Niewczas MA , Kretzler M , Mauer M , Doria A , Najafian B , Kulkarni RN , Duffin KL , Pezzolesi MG , Kahn CR , Nelson RG , Krolewski AS . J Am Soc Nephrol 2021 32 (9) 2331-2351 BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition. |
Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance
Kaur R , Gierke R , McGee L , Gonzalez E , Kobayashi M , Pichichero M . J Infect Dis 2024 BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD. |
Outpatient visits and antibiotic use due to higher valency pneumococcal vaccine serotypes
King LM , Andrejko KL , Kabbani S , Tartof SY , Hicks LA , Cohen AL , Kobayashi M , Lewnard JA . J Infect Dis 2024 BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national healthcare surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. PCV15/20-additional serotypes account for 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use. |
ACIP Updates: Recommendations for Use of 20-Valent Pneumococcal Conjugate Vaccine in Children - United States, 2023
Centers for Disease Control and Prevention , Farrar J , Gierke R , Andrejko K , Ayabina D , Zielinski L , Cohen A , Kobayashi M . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1072 On June 22, 2023, the Advisory Committee on Immunization Practices (ACIP) convened and approved recommendations for the use of 20-valent pneumococcal conjugate vaccine (PCV20 [Prevnar 20; Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.]) in U.S. children. The ACIP recommendations were adopted by the CDC Director on June 27, 2023, and are official. The recommendations, underlying evidence and rationale, and clinical guidance are available (Supplementary Report, https://stacks.cdc.gov/view/cdc/133252). |
Notes from the field: A cluster of multi-strain invasive pneumococcal disease among persons experiencing homelessness and use of pneumococcal conjugate vaccine - El Paso County, Colorado, 2022
Callaway J , Durbin K , Zachary H , Barnes MM , Kobayashi M , Chochua S , Gayou N , Albanese B . MMWR Morb Mortal Wkly Rep 2023 72 (46) 1277-1278 Persons experiencing homelessness are often at increased risk for invasive pneumococcal disease (IPD)* due to underlying health conditions or risk factors (risk conditions) (1,2). Homelessness alone is not an indication for pneumococcal vaccination according to current Advisory Committee on Immunization Practices (ACIP) recommendations (3): adults aged ≥65 years or 19–64 years with certain underlying medical conditions or risk factors† with no previous or unknown history of receipt of pneumococcal conjugate vaccine (PCV) should receive 1 dose of either 20-valent or 15-valent PCV (PCV20 or PCV15, respectively). On November 29, 2022, El Paso (Colorado) County Public Health (EPCPH) was informed by a single hospital of three cases of IPD among persons experiencing homelessness, with all illness onset dates occurring within a single week. |
The present and future of the adult pneumococcal vaccine program in the United States
Miwako Kobayashi , Cohen Adam L , Poehling Katherine A . NEJM Evidence 2023 2 (11) 11-11 Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial respiratory infections, such as pneumonia, sinusitis, and acute otitis media, and it also causes invasive diseases (i.e., infection in a normally sterile site), such as meningitis and bacteremia, leading to substantial morbidity and mortality. Before the coronavirus disease 2019 (Covid-19) pandemic, it is estimated that ≥100,000 pneumococcal pneumonia hospitalizations, ≥30,000 invasive pneumococcal disease cases, and 3000 invasive pneumocococcal disease deaths occurred among U.S. adults in a year.1 Resurgence of non-SARS-CoV-2 respiratory virus infections was reported in the United States in late 2022, and preliminary invasive pneumocococcal disease incidence in late 2022 exceeded the pre--Covid-19 baseline incidence in children and young adults (Centers for Disease Control and Prevention Active Bacterial Core surveillance, unpublished data). Effective pneumococcal vaccines are available and have been used in many countries. Although children have been the focus of pneumococcal vaccination programs globally,2 pneumococcal vaccines have also been recommended for adults in the United States for more than 40 years. The Advisory Committee on Immunization Practices updated their adult pneumococcal vaccine recommendations in October 2022, the fifth time since 2012 (Table 1), with the goal of increasing population-level protection against pneumococcal disease as well as reducing disparities in pneumococcal disease burden among those at increased risk.3 What have we learned from the U.S. adult pneumococcal vaccine program, what are the remaining gaps, and how can we address these gaps in considering future U.S. pneumococcal vaccine recommendations? Adult Pneumococcal Vaccine Program in the United States Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial respiratory infections leading to substantial morbidity and mortality. Here, Kobayashi et al. discuss the recently updated U.S. guidelines for adult pneumococcal vaccination. |
Health care provider knowledge and attitudes regarding adult pneumococcal conjugate vaccine recommendations - United States, September 28-October 10, 2022
Kahn R , Zielinski L , Gedlinske A , Askelson NM , Petersen C , Parker AM , Gidengil CA , Albert AP , Jiles AJ , Lindley MC , Kobayashi M , Scherer AM . MMWR Morb Mortal Wkly Rep 2023 72 (36) 979-984 Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence. |
Pneumococcal vaccine for adults aged 19 years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023
Kobayashi M , Pilishvili T , Farrar JL , Leidner AJ , Gierke R , Prasad N , Moro P , Campos-Outcalt D , Morgan RL , Long SS , Poehling KA , Cohen AL . MMWR Recomm Rep 2023 72 (3) 1-39 This report compiles and summarizes all published recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) for use of pneumococcal vaccines in adults aged ≥19 years in the United States. This report also includes updated and new clinical guidance for implementation from CDC. | | Before 2021, ACIP recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone (up to 2 doses), or both a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) in combination with 1–3 doses of PPSV23 in series (PCV13 followed by PPSV23), for use in U.S. adults depending on age and underlying risk for pneumococcal disease. In 2021, two new pneumococcal conjugate vaccines (PCVs), a 15-valent and a 20-valent PCV (PCV15 and PCV20), were licensed for use in U.S. adults aged ≥18 years by the Food and Drug Administration. | | ACIP recommendations specify the use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years and for adults aged 19–64 years with certain underlying medical conditions or other risk factors who have not received a PCV or whose vaccination history is unknown. In addition, ACIP recommends use of either a single dose of PCV20 or ≥1 dose of PPSV23 for adults who have started their pneumococcal vaccine series with PCV13 but have not received all recommended PPSV23 doses. Shared clinical decision-making is recommended regarding use of a supplemental PCV20 dose for adults aged ≥65 years who have completed their recommended vaccine series with both PCV13 and PPSV23. | | Updated and new clinical guidance for implementation from CDC includes the recommendation for use of PCV15 or PCV20 for adults who have received PPSV23 but have not received any PCV dose. The report also includes clinical guidance for adults who have received 7-valent PCV (PCV7) only and adults who are hematopoietic stem cell transplant recipients. |
Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines (preprint)
Lewnard JA , Patel MM , Jewell NP , Verani JR , Kobayashi M , Tenforde MW , Dean NE , Cowling BJ , Lopman BA . medRxiv 2021 2021.01.21.21250258 Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. These are now in planning amid the ongoing rollout of SARS-CoV-2 vaccines globally. While traditional case-control (TCC) and test-negative design (TND) studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here we review the theoretical basis for estimation of vaccine direct effects under TCC and TND frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, non-specific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The TCC may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The TND reduces but may not eliminate this confounding, for instance if individuals who receive vaccination seek care or testing for less-severe infection. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.Competing Interest StatementJAL has received grants and consulting fees from Pfizer, Inc. unrelated to this research.Funding StatementThis work was supported by grants R01-AI14812701 from the National Institute for Allergy and Infectious Diseases to NPJ and JAL, and R01-AI139761 from the National Institute for Allergy and Infectious Diseases to NED.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:N/AAll 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.YesThis is a theoretical study without patient data; equations used to generate the figures appear in the manuscript. |
mRNA Vaccine Effectiveness against COVID-19 among Symptomatic Outpatients Aged ≥16 Years in the United States, February – May 2021 (preprint)
Kim SS , Chung JR , Belongia EA , McLean HQ , King JP , Nowalk MP , Zimmerman RK , Balasubramani GK , Martin ET , Monto AS , Lamerato LE , Gaglani M , Smith ME , Dunnigan KM , Jackson ML , Jackson LA , Tenforde MW , Verani JR , Kobayashi M , Schrag S , Patel MM , Flannery B . medRxiv 2021 2021.07.20.21260647 Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.Competing Interest StatementMPN reports grants from Merck & Co. outside the submitted work. RKZ reports grants from Sanofi Pasteur outside the submitted work. GKB reports grants from Merck & Co outside the submitted work and consulting fees from New World Medical, LLC. ETM reports grants from Merck & Co. outside the submitted work and consulting fees from Pfizer. ASM reports consulting fees from Sanofi Pasteur and Seqirus. LEL reports grants from Xcenda, Inc., eMAXHealth, AstraZeneca, Pfizer, Evidera outside the submitted work. MLJ reports grants from Sanofi Pasteur. All other authors report nothing to disclose.Funding StatementThis work was supported by the US Centers for Disease Control and Prevention through cooperative agreements U01IP001034-U01IP001039. At Pittsburgh, the project was also supported by the National Institutes of Health through grant ULTR001857.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:Centers for Disease Control and Prevention IRB project determination numbers for included projects: 0900f3eb81c2e791, 0900f3eb81c52dc5; 0900f3eb81c52420, 0900f3eb81bc746b, 6238All 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.YesDe-identified dataset can be made available upon request |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll 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.YesData may be available upon reasonable request. |
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults (preprint)
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . medRxiv 2022 07 The 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) were previously recommended for adults in the United States. To help inform discussions on recently licensed 15- and 20-valent pneumococcal vaccine use among adults, we conducted a systematic review of PCV13 and PPSV23 efficacy or effectiveness. We conducted a search on PCV13 and PPSV23 efficacy or effectiveness (VE) studies against vaccine type (VT) invasive pneumococcal disease (IPD) and VT-pneumococcal pneumonia in adults. Nineteen studies were included: 13 on VT-IPD (four on PCV13, nine on PPSV23) and eight on VT- pneumococcal pneumonia (three on PCV13, four on PPSV23, one on PCV13 and PPSV23). One randomized-controlled trial (RCT) evaluated PCV13 and observed an efficacy of 75% and 45% against VT-IPD and VT-pneumococcal pneumonia, respectively. No RCTs reported PPSV23 efficacy. PCV13 effectiveness estimates against VTIPD ranged from 47% to 68%. Pooled PPSV23 effectiveness against VT-IPD was 45% (95% CI: 37%, 51%; I2=0%). PCV13 VE estimates against VT-pneumonia ranged from -2 to 46%. Pooled PPSV23 VE against VT-pneumococcal pneumonia was 18% (95% CI: -4%, 35%; I2=0%). Evidence suggests PCV13 and PPSV23 are effective against VT-IPD and VT-pneumococcal pneumonia in adults; this was used to inform PCV15 and PCV20 policy decisions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States (preprint)
Tenforde MW , Patel MM , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CT , Busse L , Lohuis CCT , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Gershengorn HB , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Self WH . medRxiv 2021 BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. |
Systematic review and meta-analysis of the efficacy and effectiveness of pneumococcal vaccines in adults
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . Pathogens 2023 12 (5) New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle-Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: -4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults. |
Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021.
Tenforde MW , Self WH , Naioti EA , Ginde AA , Douin DJ , Olson SM , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Patel MM , IVY Network Investigators . MMWR Morb Mortal Wkly Rep 2021 70 (34) 1156-1162 Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination. |
Effectiveness of COVID-19 mRNA vaccines in preventing COVID-19-associated outpatient visits and hospitalizations among American indian and Alaska native persons, January-November 2021: A test-negative case-control analysis using surveillance data
Lutz CS , Hartman RM , Vigil DE , Britton A , Burrage AB , Campbell AP , Close RM , Desnoyers C , Dobson J , Garcia S , Halasa N , Honie E , Kobayashi M , McMorrow M , Mostafa HH , Parker D , Pohl K , Prill MM , Richards J , Roessler KC , Sutcliffe CG , Taylor K , Swango-Wilson A , Va P , Verani JR , Singleton RJ , Hammitt LL . Open Forum Infect Dis 2023 10 (4) ofad172 BACKGROUND: Despite the disproportionate morbidity and mortality expeHealth Equity and Health Disparitiesrienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. METHODS: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. RESULTS: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. CONCLUSIONS: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population. |
Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States
Prasad N , Stoecker C , Xing W , Cho BH , Leidner AJ , Kobayashi M . Vaccine 2023 41 (18) 2914-2921 BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States. |
Changes in the incidence of invasive bacterial disease during the COVID-19 pandemic in the United States, 2014-2020
Prasad N , Rhodes J , Deng L , McCarthy N , Moline HL , Baggs J , Reddy SC , Jernigan JA , Havers FP , Sosin D , Thomas A , Lynfield R , Schaffner W , Reingold A , Burzlaff K , Harrison LH , Petit S , Farley MM , Herlihy R , Nanduri S , Pilishvili T , McNamara LA , Schrag SJ , Fleming-Dutra KE , Kobayashi M , Arvay M . J Infect Dis 2023 227 (7) 907-916 BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. METHODS: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. RESULTS: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. CONCLUSIONS: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing. |
Association of pneumococcal conjugate vaccine use with hospitalized pneumonia in Medicare beneficiaries 65 years or older with and without medical conditions, 2014 to 2017
Kobayashi M , Spiller MW , Wu X , Wang R , Chillarige Y , Wernecke M , MaCurdy TE , Kelman JA , Deng L , Shang N , Whitney CG , Pilishvili T , Lessa FC . JAMA Intern Med 2022 183 (1) 40-47 IMPORTANCE: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. OBJECTIVE: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. DESIGN, SETTING, AND PARTICIPANTS: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. EXPOSURES: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. MAIN OUTCOMES AND MEASURES: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). RESULTS: At the end of follow-up (December 2017), 24121625 beneficiaries (13593975 women [56.4%]; 418005 [1.7%] Asian, 1750807 [4.8%] Black, 338044 [1.4%] Hispanic, 111508 [0.5%] Native American, and 20700948 [85.8%] White individuals) were in the cohort; 4936185 (20.5%) had received PCV13 only, and 10646220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35127 pneumonia (95% CI, 33011-37270), 24643 non-HA pneumonia (95% CI, 22761-26552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. CONCLUSIONS AND RELEVANCE: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults. |
Use of 15-valent pneumococcal conjugate vaccine among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022
Kobayashi M , Farrar JL , Gierke R , Leidner AJ , Campos-Outcalt D , Morgan RL , Long SS , Poehling KA , Cohen AL . MMWR Morb Mortal Wkly Rep 2022 71 (37) 1174-1181 The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(†) approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions(§) that increase the risk for pneumococcal disease have not changed. |
Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study.
Lauring AS , Tenforde MW , Chappell JD , Gaglani M , Ginde AA , McNeal T , Ghamande S , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Johnson NJ , Srinivasan V , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , TenLohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Halasa N , Grijalva CG , Rice TW , Stubblefield WB , Baughman A , Womack KN , Rhoads JP , Lindsell CJ , Hart KW , Zhu Y , Adams K , Schrag SJ , Olson SM , Kobayashi M , Verani JR , Patel MM , Self WH . BMJ 2022 376 e069761 Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Participants 11 690 adults (>=18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: Alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. Results Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants. Copyright Author(s) (or their employer(s)) 2019. |
mRNA Vaccine Effectiveness Against COVID-19 Hospitalization Among Solid Organ Transplant Recipients.
Kwon JH , Tenforde MW , Gaglani M , Talbot HK , Ginde AA , McNeal T , Ghamande S , Douin DJ , Casey JD , Mohr NM , Zepeski A , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Caspers SD , Exline MC , Botros M , Gong MN , Li A , Mohamed A , Johnson NJ , Srinivasan V , Steingrub JS , Peltan ID , Brown SM , Martin ET , Khan A , Hough CL , Busse LW , Duggal A , Wilson JG , Perez C , Chang SY , Mallow C , Rovinski R , Babcock HM , Lauring AS , Felley L , Halasa N , Chappell JD , Grijalva CG , Rice TW , Womack KN , Lindsell CJ , Hart KW , Baughman A , Olson SM , Schrag S , Kobayashi M , Verani JR , Patel MM , Self WH . J Infect Dis 2022 226 (5) 797-807 BACKGROUND: The study objective was to evaluate 2 and 3 dose COVID-19 mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. METHODS: 21-site case-control analysis of 10,425 adults hospitalized March-December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (SARS-CoV-2 negative). Participants were classified as: SOT recipient (n=440), other immunocompromising condition (n=1684), or immunocompetent (n=8301). VE against COVID-19 associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. RESULTS: Among SOT recipients, VE was 29% (95% CI: -19 to 58%) for 2 doses and 77% (95% CI: 48 to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI: 64 to 79%) for 2 doses and 92% (95% CI: 85 to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI: 87 to 90%) for 2 doses and 96% (95% CI: 83 to 99%) for 3 doses. CONCLUSION: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent people and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses. |
Impact of 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among adults with HIV-United States, 2008-2018
Kobayashi M , Matanock A , Xing W , Adih WK , Li J , Gierke R , Almendares O , Reingold A , Alden N , Petit S , Farley MM , Harrison LH , Holtzman C , Baumbach J , Thomas A , Schaffner W , McGee L , Pilishvili T . J Acquir Immune Defic Syndr 2022 90 (1) 6-14 BACKGROUND: People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. METHODS: We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. RESULTS: In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. CONCLUSIONS: Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH. |
Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. Adults: Updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022
Kobayashi M , Farrar JL , Gierke R , Britton A , Childs L , Leidner AJ , Campos-Outcalt D , Morgan RL , Long SS , Talbot HK , Poehling KA , Pilishvili T . MMWR Morb Mortal Wkly Rep 2022 71 (4) 109-117 In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework,(†) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(§) approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations. |
Symptoms in blastomycosis, coccidioidomycosis, and histoplasmosis versus other respiratory illnesses in commercially insured adult outpatients-United States, 2016-2017
Benedict K , Kobayashi M , Garg S , Chiller T , Jackson BR . Clin Infect Dis 2021 73 (11) e4336-e4344 BACKGROUND: Blastomycosis, coccidioidomycosis, and histoplasmosis cause various symptoms and syndromes, which may present similarly to other infections such as bacterial or viral community-acquired pneumonia, influenza, and tuberculosis. METHODS: We used the IBM MarketScan Research Databases to identify adult outpatients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), diagnosis codes during 2016-2017 for blastomycosis, coccidioidomycosis, histoplasmosis, pneumonia (viral, bacterial, Streptococcus pneumoniae, and unspecified pneumonia), influenza; tuberculosis, and other lower and upper respiratory infections. We compared symptoms on and in the 90 days before diagnosis between patients with these diagnosis codes. RESULTS: Fever was less common in blastomycosis (2.6%), histoplasmosis (5.3%), and coccidioidomycosis (9.4%) than in patients with influenza (18.5%) or pneumonia (12.6-16.3%). Fungal diseases resembled bacterial, viral, and unspecified pneumonias for many pulmonary symptoms. However, cough was more common with coccidioidomycosis (31.4%) and less common with histoplasmosis (14.0%) and blastomycosis (13.1%) versus influenza (20.2%). Although less frequent, solitary pulmonary nodule (5.2-14.4%), enlarged lymph nodes (3.7-9.0%), hyperhidrosis (<2%), and erythema nodosum (<2%) were particularly suggestive of fungal diseases. CONCLUSIONS: Despite limitations inherent in administrative coding, this analysis of symptom codes across disease types suggests that fungal diseases may be difficult to clinically distinguish from other causes of pneumonia except when certain uncommon symptoms are present. Healthcare providers caring for patients with pneumonia, especially if nonresponsive to conventional treatment, should consider fungal diseases as possible etiologies. |
Effectiveness of mRNA vaccines in preventing COVID-19 hospitalization by age and burden of chronic medical conditions among immunocompetent US adults, March-August 2021.
Lewis NM , Naioti EA , Self WH , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , Ghamande SA , McNeal TA , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Hubel K , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Rhoads JP , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Schrag SJ , Kobayashi M , Verani JR , Patel MM , Tenforde MW . J Infect Dis 2021 225 (10) 1694-1700 In a multi-state network, vaccine effectiveness (VE) against COVID-19 hospitalizations was evaluated among immunocompetent adults (≥18-years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was higher at 96% (95% CI: 93-98%) among patients with no chronic medical conditions than patients with ≥3 categories of conditions (83% [95% CI: 76-88%]). VE was similar between those aged 18-64 years vs ≥65 years (p>0.05). Vaccine effectiveness against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing burden of comorbidities. |
Comparative Effectiveness and Antibody Responses to Moderna and Pfizer-BioNTech COVID-19 Vaccines among Hospitalized Veterans - Five Veterans Affairs Medical Centers, United States, February 1-September 30, 2021.
Bajema KL , Dahl RM , Evener SL , Prill MM , Rodriguez-Barradas MC , Marconi VC , Beenhouwer DO , Holodniy M , Lucero-Obusan C , Brown ST , Tremarelli M , Epperson M , Mills L , Park SH , Rivera-Dominguez G , Morones RG , Ahmadi-Izadi G , Deovic R , Mendoza C , Jeong C , Schrag SJ , Meites E , Hall AJ , Kobayashi M , McMorrow M , Verani JR , Thornburg NJ , Surie D . MMWR Morb Mortal Wkly Rep 2021 70 (49) 1700-1705 The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.(†). |
Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity.
Tenforde MW , Self WH , Adams K , Gaglani M , Ginde AA , McNeal T , Ghamande S , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Rhoads JP , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Kobayashi M , Verani JR , Patel MM . JAMA 2021 326 (20) 2043-2054 IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58). CONCLUSIONS AND RELEVANCE: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination. |
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions - United States, March-August 2021.
Self WH , Tenforde MW , Rhoads JP , Gaglani M , Ginde AA , Douin DJ , Olson SM , Talbot HK , Casey JD , Mohr NM , Zepeski A , McNeal T , Ghamande S , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CL , Busse LW , Ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Exline MC , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Mills L , Lester SN , Stumpf MM , Naioti EA , Kobayashi M , Verani JR , Thornburg NJ , Patel MM . MMWR Morb Mortal Wkly Rep 2021 70 (38) 1337-1343 Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization. |
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