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Caballero N, Monsalve DM, Acosta-Ampudia Y, Fajardo N, Moreno S, Martínez O, González-Uribe C, Ramírez-Santana C, Quintero J. Long-term dynamics of SARS-CoV-2 immunity in a university hospital in Colombia: A cohort study. IJID REGIONS 2025; 15:100641. [PMID: 40391349 PMCID: PMC12088765 DOI: 10.1016/j.ijregi.2025.100641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 03/20/2025] [Accepted: 03/22/2025] [Indexed: 05/21/2025]
Abstract
Objectives This prospective cohort study aimed to estimate the natural, vaccine-induced, and hybrid immunity to SARS-CoV-2, alongside the immunogenicity of the messenger RNA (mRNA)-1273 booster after the BNT162b2 primary series in health care workers in Colombia. Methods Immunoglobulin (Ig) G, IgA, and neutralizing antibodies were measured in 110 individuals with SARS-CoV-2 infection or a BNT162b2 primary series. Humoral responses and related factors were explored in a subgroup (n = 36) that received a BNT162b2 primary series, followed by a mRNA-1273 booster (2BNT162b2 + 1mRNA-1273), and T-cell responses were evaluated in a subgroup of them (n = 16). Results For natural immunity, IgG and IgA peaked within 3 months, declining gradually but remaining detectable up to 283 days post-infection. Neutralizing antibody inhibition post-infection was below positive range (≥35%) but exceeded 97% in vaccine-induced and hybrid immunity groups. After 2BNT162b2 + 1mRNA-1273, IgG peaked 3-4 months post-booster, gradually declining but remaining positive over 10 months, with IgA and neutralizing antibodies stable. Age and blood group were related to IgG response, whereas obesity and blood type were related to IgA response post-booster. Autoimmunity and blood type B were associated with lower neutralizing antibody inhibition. There were no differences in T-cell responses according to previous infection. Conclusions These findings provide long-term insights into the immunity against SARS-CoV-2 and the immunogenicity of mRNA vaccines.
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Affiliation(s)
- Nohemi Caballero
- Population Health, Fundación Santa Fe de Bogotá, Bogotá, Colombia
- School of Medicine, Universidad de los Andes, Bogotá, Colombia
| | - Diana M. Monsalve
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Yeny Acosta-Ampudia
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Natalia Fajardo
- School of Medicine, Universidad de los Andes, Bogotá, Colombia
| | - Sergio Moreno
- School of Medicine, Universidad de los Andes, Bogotá, Colombia
| | - Oscar Martínez
- Department of Pathology and Laboratories, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | | | - Carolina Ramírez-Santana
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Juliana Quintero
- Population Health, Fundación Santa Fe de Bogotá, Bogotá, Colombia
- Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia
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Pelczyńska M, Moszak M, Wojciechowska J, Płócienniczak A, Potocki J, Blok J, Balcerzak J, Zblewski M, Bogdański P. The Role of the Chronotype in Developing an Excessive Body Weight and Its Complications-A Narrative Review. Nutrients 2024; 17:80. [PMID: 39796515 PMCID: PMC11723089 DOI: 10.3390/nu17010080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
The chronotype, the personal predisposition towards morning or evening activities, significantly influences health conditions, sleep, and eating regulations. Individuals with evening chronotypes are often at a higher risk for weight gain due to misalignment between their natural tendencies of functioning and social schedules, resulting in insufficient sleep, disruptions in eating habits, and decreased physical activity levels. Often, impaired glucose tolerance and changes in melatonin, adiponectin, and leptin secretion, along with alterations in the clock gene functions in subjects with evening preferences, may be predisposed to obesity. These disturbances contribute to metabolic dysregulation, which may lead to the subsequent onset of obesity complications, such as hypertension, type 2 diabetes, sleep apnea, and liver diseases. Targeting critical components of the circadian system and synchronizing people's chronotypes with lifestyle conditions could deliver potential strategies for preventing and treating metabolic disorders. Thus, it is recommended to take a personalized chronobiological approach to maintain a normal body weight and metabolic health. Nevertheless, future studies are needed to identify the clear mechanisms between the chronotype and human health. This article provides a narrative review and discussion of recent data to summarize studies on the circadian rhythm in the context of obesity. The manuscript represents a comprehensive overview conducted between August and November 2024 using the National Library of Medicine browser (Medline, Pub-Med, Web of Science).
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Affiliation(s)
- Marta Pelczyńska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznań University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland; (M.M.); (P.B.)
| | - Małgorzata Moszak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznań University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland; (M.M.); (P.B.)
| | - Julita Wojciechowska
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Anita Płócienniczak
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Jan Potocki
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Joanna Blok
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Julia Balcerzak
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Mikołaj Zblewski
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznan, Poland; (J.W.); (A.P.); (J.P.); (J.B.); (J.B.); (M.Z.)
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznań University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland; (M.M.); (P.B.)
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Ouattara NGM, Sanou AM, Napon-Zongo D, Coulibaly A, Korogho S, Dera A, Nikièma AS, Kyelem E, Gansoré N, Ilboudo AK, Diendéré J, Ouédraogo GH. Immune response to GeneVac-B Ⓡ (rDNA I.P. hepatitis B vaccine) in vaccinated persons with a standard schedule in Bobo-Dioulasso, Burkina Faso. IJID REGIONS 2024; 13:100483. [PMID: 39639948 PMCID: PMC11618024 DOI: 10.1016/j.ijregi.2024.100483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/23/2024] [Accepted: 10/23/2024] [Indexed: 12/07/2024]
Abstract
Objective This study aimed to evaluate the immune response in people fully vaccinated against hepatitis B with the GeneVac-BⓇ vaccine in Burkina Faso under actual conditions of use. Methods This cross-sectional study included individuals fully vaccinated with GeneVac-BⓇ. For each consenting participant, sociodemographic and clinical data were collected using a structured questionnaire. Approximately 4 ml of whole blood was collected for immunological (anti-HBs, hepatitis B surface antigen, anti-hepatitis C virus, and anti-HIV) and biochemical (blood glucose, total cholesterol, and triglycerides) testing. The anti-HBs titer was used to determine the immune response. Results A total of 392 participants were included in the study. The mean age was 35.5 ± 15.3 years. Approximately 56% had been previously exposed to hepatitis B virus. Overall, 380 participants had an anti-HBs titer ≥ 12 mIU/ml indicating a seroprotection rate of 96.9%, and 12 had a titer <12 mIU/ml, a nonresponse rate of 3.1%. Among the nonresponders, 11 (11/12; 91.7%) had high total cholesterol levels (>240 mg/dl), and 8 (8/12; 66.7%) were older than 40 years of age. Conclusions The results showed an excellent immune response to GeneVac-BⓇ in our study population. However, age > 40 and high total cholesterol appear to be factors associated with nonresponse.
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Affiliation(s)
- Nina Genéviève Mathuola Ouattara
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
- Département des Laboratoires, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
| | - Armel Moumouni Sanou
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
- Département des Laboratoires, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
| | - Delphine Napon-Zongo
- Département Clinique, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
- Institut Supérieur des Sciences de la Santé (INSSA), Université́ Nazi Boni, Bobo-Dioulasso, Burkina Faso
| | - Abou Coulibaly
- Laboratoire de Recherche en Santé Publique et Nutrition (LR-SPN), Bobo-Dioulasso, Burkina Faso
| | - Sylviane Korogho
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
| | - Abdoulaye Dera
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
- Département des Laboratoires, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
| | - Achille S. Nikièma
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
| | - Eric Kyelem
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Bobo-Dioulasso, Burkina Faso
| | - Nawatou Gansoré
- Département Clinique, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
| | - Abdoul Kader Ilboudo
- Département Méthodologie et Gestion des Données, Centre “Assaut-Hépatites”, Bobo-Dioulasso, Burkina Faso
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Ouagadougou, Burkina Faso
| | - Jeoffray Diendéré
- Laboratoire de Recherche en Santé Publique et Nutrition (LR-SPN), Bobo-Dioulasso, Burkina Faso
| | - Gautier Henri Ouédraogo
- Laboratoire de Recherche sur les Maladies Infectieuses et Parasitaire (LR-MIP), Institut de Recherche en Science de la Santé, Ouagadougou, Burkina Faso
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Clarke M, Mathew SM, Giles LC, Barr IG, Richmond PC, Marshall HS. The Impact of Obesity on Influenza Vaccine Immunogenicity and Antibody Transfer to the Infant During Pregnancy. Vaccines (Basel) 2024; 12:1307. [PMID: 39771969 PMCID: PMC11680122 DOI: 10.3390/vaccines12121307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/07/2024] [Accepted: 11/18/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES Influenza vaccination is recommended for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza. This study aimed to investigate the impact of body mass index (BMI) on influenza vaccine responses in pregnant women and their newborns. METHODS Participants included pregnant women attending the Women's and Children's Hospital in South Australia between 2018 and 2021. Maternal blood samples were collected prior to and at 1 and 6 months post-influenza vaccination to measure antibody responses by hemagglutination inhibition (HI) assay. Cord blood samples were also collected. The percentages of participants achieving HI titre ≥40 were compared between obese and non-obese groups. RESULTS A total of 73 women were enrolled and received quadrivalent influenza vaccination at a mean age of 32 years (range 21-44 y) and median gestation of 24 weeks (range 11-37 weeks). BMI at vaccination was ≥30 kg/m2 for 21/73 women (29%). Most pregnant women demonstrated antibody titres ≥ 40 to all four influenza vaccine strains at 1 month post-vaccination regardless of BMI category (BMI ≥ 30 kg/m2: 19/20; 95% vs. BMI < 30 kg/m2: 47/49; 96%). At 6 months post-vaccination, 12/17 (71%) obese women compared to 36/43 (84%) non-obese women (p = 0.25) maintained HI titres ≥ 40. Cord blood serology showed HI titres ≥ 40 for 11/17 (65%) infants born to mothers with BMI ≥ 30 compared to 30/35 (86%) infants delivered by mothers with BMI < 30 kg/m2. CONCLUSIONS A high BMI did not impair influenza vaccine antibody responses in pregnant women at 1 month post-vaccination. However, at 6 months post-vaccination, and in the cord blood samples, the percentages maintaining HI titre ≥ 40 were lower for obese women than for non-obese pregnant women.
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Affiliation(s)
- Michelle Clarke
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.)
- The Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
| | - Suja M. Mathew
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.)
- The Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
| | - Lynne C. Giles
- School of Public Health, The University of Adelaide, Adelaide, SA 5005, Australia;
| | - Ian G. Barr
- WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute, Melbourne, VIC 3000, Australia;
| | - Peter C. Richmond
- Discipline of Pediatrics, University of Western Australia, Perth, WA 6009, Australia;
- Wesfarmers Centre of Vaccines and Infectious Diseases, Kids Research Institute of Australia, Perth Children’s Hospital, Perth, WA 6009, Australia
| | - Helen S. Marshall
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.)
- The Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
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King JP, Nguyen HQ, Kiniry EL, Phillips CH, Gaglani M, Martin ET, Geffel KM, Nowalk MP, Chung JR, Flannery B, Belongia EA. Elevated body mass index is not significantly associated with reduced influenza vaccine effectiveness. Sci Rep 2024; 14:21466. [PMID: 39271784 PMCID: PMC11399117 DOI: 10.1038/s41598-024-72081-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011-12 through 2017-18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m2), overweight (25-29 kg/m2), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1-adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16-31, 46-54, and 44-57%, and in children from 29-34, 57-65, and 50-55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.
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Affiliation(s)
- Jennifer P King
- Center for Clinical Epidemiology & Population Health, Marshfield Clinic Research Institute (ML2), 1000 N. Oak Ave, Marshfield, WI, 54449, USA.
| | - Huong Q Nguyen
- Center for Clinical Epidemiology & Population Health, Marshfield Clinic Research Institute (ML2), 1000 N. Oak Ave, Marshfield, WI, 54449, USA
| | - Erika L Kiniry
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - C Hallie Phillips
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Manjusha Gaglani
- Baylor College of Medicine, Baylor Scott & White Health, Dallas, TX, USA
- Texas A&M University College of Medicine, Temple, TX, USA
| | - Emily T Martin
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | | | | | - Jessie R Chung
- Influenza Division, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Brendan Flannery
- Influenza Division, US Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Edward A Belongia
- Center for Clinical Epidemiology & Population Health, Marshfield Clinic Research Institute (ML2), 1000 N. Oak Ave, Marshfield, WI, 54449, USA
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Soponkanabhorn T, Suratannon N, Buranapraditkun S, Tubjareon C, Prachuapthunyachart S, Eiamkulbutr S, Chongsrisawat V. Cellular immune response to a single dose of live attenuated hepatitis a virus vaccine in obese children and adolescents. Heliyon 2024; 10:e36610. [PMID: 39258209 PMCID: PMC11385843 DOI: 10.1016/j.heliyon.2024.e36610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 08/19/2024] [Accepted: 08/19/2024] [Indexed: 09/12/2024] Open
Abstract
Background Limited data are currently available regarding the cellular immune response to a live attenuated hepatitis A virus (HAV) vaccine, especially in children with obesity. The objective of this retrospective cohort study was to compare the activation of antigen-specific interferon (IFN)-γ+ T cells in obese children and adolescents with healthy individuals before and after immunization with a single dose of live attenuated HAV vaccine. Methods Blood samples were obtained from the 2021 study by Dumrisilp et al. investigating the immunogenicity of the live attenuated hepatitis A vaccine in children and young adults. Prior to enrollment, all 212 subjects had never received any HAV vaccine and tested negative for anti-HAV antibodies. The participants were vaccinated with a freeze-dried, live attenuated HAV vaccine of the H2 strain. In this study, we analyzed the stored peripheral blood mononuclear cells (PBMCs) obtained from a subgroup of 30 obese subjects and 30 normal-weight healthy controls of the same age and sex. PBMCs were collected before and 8-9 weeks after HAV vaccination for further analysis. These cells were stimulated with a recombinant antigen derived from HAV-VP3, and the immune response was evaluated using the IFN-γ enzyme-linked immunospot (ELISpot) assay. Results The between-group analysis indicated that the T-cell response of obese participants was comparable to that of normal-weight controls both before and after vaccination. The change in IFN-γ production from before to after vaccination in the obese group was not significantly different from that of the control group. Additionally, in the obese group, no correlation was found between IFN-γ production and clinical characteristics such as sex, body mass index, waist circumference, and acanthosis nigricans. Conclusion Testing for cellular immune response provides a comprehensive understanding of the overall immune response to vaccination. This study, the first to explore this significant aspect, suggests that obesity does not affect the short-term cellular immune response to live attenuated HAV vaccination.
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Affiliation(s)
- Tanatchabhorn Soponkanabhorn
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Narissara Suratannon
- Center of Excellence for Allergy and Clinical Immunology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Supranee Buranapraditkun
- Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chomchanat Tubjareon
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Sittichoke Prachuapthunyachart
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Sutha Eiamkulbutr
- Excellence Center of Organ Transplantation, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Voranush Chongsrisawat
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
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Gromer DJ, Plikaytis BD, McCullough MP, Wimalasena ST, Rouphael N. The Relationship between Immunogenicity and Reactogenicity of Seasonal Influenza Vaccine Using Different Delivery Methods. Vaccines (Basel) 2024; 12:809. [PMID: 39066447 PMCID: PMC11281354 DOI: 10.3390/vaccines12070809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/13/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.
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Affiliation(s)
- Daniel J. Gromer
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (M.P.M.); (S.T.W.); (N.R.)
- Laney Graduate School, Emory University, Atlanta, GA 30307, USA
| | | | - Michele P. McCullough
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (M.P.M.); (S.T.W.); (N.R.)
| | - Sonia Tandon Wimalasena
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (M.P.M.); (S.T.W.); (N.R.)
| | - Nadine Rouphael
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (M.P.M.); (S.T.W.); (N.R.)
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Castro-Balado A, Varela-Rey I, Mejuto B, Mondelo-García C, Zarra-Ferro I, Rodríguez-Jato T, Fernández-Ferreiro A. Updated antimicrobial dosing recommendations for obese patients. Antimicrob Agents Chemother 2024; 68:e0171923. [PMID: 38526051 PMCID: PMC11064535 DOI: 10.1128/aac.01719-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024] Open
Abstract
The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.
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Affiliation(s)
- Ana Castro-Balado
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Iria Varela-Rey
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Beatriz Mejuto
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Cristina Mondelo-García
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Irene Zarra-Ferro
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Teresa Rodríguez-Jato
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Anxo Fernández-Ferreiro
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
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van Brakel L, Mensink RP, Lütjohann D, Plat J. Plant stanol consumption increases anti-COVID-19 antibody responses, independent of changes in serum cholesterol concentrations: a randomized controlled trial. Am J Clin Nutr 2024; 119:969-980. [PMID: 38278364 DOI: 10.1016/j.ajcnut.2024.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 01/15/2024] [Accepted: 01/23/2024] [Indexed: 01/28/2024] Open
Abstract
BACKGROUND People with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown. OBJECTIVES We evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. METHODS A double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. RESULTS IgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed. CONCLUSIONS Consuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption. This trial was registered at clinicaltrials.gov as NCT04844346.
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Affiliation(s)
- Lieve van Brakel
- Department of Nutrition and Movement Sciences, NUTRIM School of Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
| | - Ronald P Mensink
- Department of Nutrition and Movement Sciences, NUTRIM School of Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Dieter Lütjohann
- Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany
| | - Jogchum Plat
- Department of Nutrition and Movement Sciences, NUTRIM School of Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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10
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Johnson RM, Ardanuy J, Hammond H, Logue J, Jackson L, Baracco L, McGrath M, Dillen C, Patel N, Smith G, Frieman M. Diet-induced obesity and diabetes enhance mortality and reduce vaccine efficacy for SARS-CoV-2. J Virol 2023; 97:e0133623. [PMID: 37846985 PMCID: PMC10688338 DOI: 10.1128/jvi.01336-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 09/09/2023] [Indexed: 10/18/2023] Open
Abstract
IMPORTANCE Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a wide spectrum of diseases in the human population, from asymptomatic infections to death. It is important to study the host differences that may alter the pathogenesis of this virus. One clinical finding in coronavirus disease 2019 (COVID-19) patients is that people with obesity or diabetes are at increased risk of severe illness from SARS-CoV-2 infection. We used a high-fat diet model in mice to study the effects of obesity and type 2 diabetes on SARS-CoV-2 infection as well as how these comorbidities alter the response to vaccination. We find that diabetic/obese mice have increased disease after SARS-CoV-2 infection and they have slower clearance of the virus. We find that the lungs of these mice have increased neutrophils and that removing these neutrophils protects diabetic/obese mice from disease. This demonstrates why these diseases have increased risk of severe disease and suggests specific interventions upon infection.
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Affiliation(s)
- Robert M. Johnson
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Jeremy Ardanuy
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Holly Hammond
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - James Logue
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Lian Jackson
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Lauren Baracco
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Marisa McGrath
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Carly Dillen
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | | | | | - Matthew Frieman
- Center for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
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11
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Santoni M, Massari F, Myint ZW, Iacovelli R, Pichler M, Basso U, Kopecky J, Kucharz J, Buti S, Salfi A, Büttner T, De Giorgi U, Kanesvaran R, Fiala O, Grande E, Zucali PA, Fornarini G, Bourlon MT, Scagliarini S, Molina-Cerrillo J, Aurilio G, Matrana MR, Pichler R, Cattrini C, Büchler T, Seront E, Calabrò F, Pinto A, Berardi R, Zgura A, Mammone G, Ansari J, Atzori F, Chiari R, Zakopoulou R, Caffo O, Procopio G, Bassanelli M, Zampiva I, Messina C, Küronya Z, Mosca A, Bhuva D, Vau N, Incorvaia L, Rebuzzi SE, Roviello G, Zabalza IO, Rizzo A, Mollica V, Catalini I, Monteiro FSM, Montironi R, Battelli N, Rizzo M, Porta C. Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Oncology Combinations (ARON-1). Clin Genitourin Cancer 2023; 21:e309-e319.e1. [PMID: 37062658 DOI: 10.1016/j.clgc.2023.03.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 03/14/2023] [Accepted: 03/14/2023] [Indexed: 04/18/2023]
Abstract
BACKGROUND Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. RESULTS A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). CONCLUSION Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.
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Affiliation(s)
| | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.
| | - Zin W Myint
- Markey Cancer Center, University of Kentucky, Lexington, KY
| | - Roberto Iacovelli
- Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Martin Pichler
- Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Umberto Basso
- Oncology 3 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Jindrich Kopecky
- Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
| | - Jakub Kucharz
- Department of Uro-oncology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Warsaw, Poland
| | - Sebastiano Buti
- Medical Oncology Unit, University Hospital of Parma - Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Alessia Salfi
- Oncology Unit 2, University Hospital of Pisa, Pisa, Italy
| | - Thomas Büttner
- Department of Urology, University Hospital Bonn (UKB), Bonn, Germany
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | | | - Ondřej Fiala
- Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic
| | - Enrique Grande
- Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain
| | - Paolo Andrea Zucali
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | | | - Maria T Bourlon
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Sarah Scagliarini
- UOC di Oncologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli di Napoli, Naples, Italy
| | | | - Gaetano Aurilio
- Medical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Marc R Matrana
- Department of Internal Medicine, Hematology/Oncology, Ochsner Medical Center, New Orleans, LA
| | - Renate Pichler
- Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Carlo Cattrini
- Department of Medical Oncology, "Maggiore della Carità" University Hospital, Novara, Italy
| | - Tomas Büchler
- Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic
| | - Emmanuel Seront
- Department of Medical Oncology, Centre Hospitalier de Jolimont, Belgium
| | - Fabio Calabrò
- Department of Oncology, San Camillo Forlanini Hospital, Rome, Italy
| | - Alvaro Pinto
- Medical Oncology Department, La Paz University Hospital, Madrid, Spain
| | - Rossana Berardi
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti delle Marche, Ancona, Italy
| | - Anca Zgura
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Giulia Mammone
- Department of Radiological, Oncological and Anatomo-Pathological Science, "Sapienza" University of Rome, Rome, Italy
| | - Jawaher Ansari
- Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Francesco Atzori
- Unità di Oncologia Medica, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy
| | - Rita Chiari
- UOC Oncologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Italy
| | - Roubini Zakopoulou
- 2nd Propaedeutic Dept of Internal Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Orazio Caffo
- Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy
| | - Giuseppe Procopio
- Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Oncologia Medica, Ospedale Maggiore di Cremona, Italy
| | - Maria Bassanelli
- Medical Oncology 1-IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Ilaria Zampiva
- Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy
| | | | - Zsófia Küronya
- Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary
| | | | - Dipen Bhuva
- Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India
| | - Nuno Vau
- Urologic Oncology, Champalimaud Clinical Center, Lisbon, Portugal
| | - Lorena Incorvaia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Sara Elena Rebuzzi
- Ospedale San Paolo, Medical Oncology, Savona, Italy; Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
| | - Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
| | | | - Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia
| | | | - Fernando Sabino M Monteiro
- Latin American Cooperative Oncology Group - LACOG; Oncology and Hematology Department, Hospital Santa Lucia, Brasília, Federal District, Brazil
| | - Rodolfo Montironi
- Molecular Medicine and Cell Therapy Foundation, Polytechnic University of the Marche Region, Ancona, Italy
| | | | - Mimma Rizzo
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Camillo Porta
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy; Chair of Oncology, Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
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12
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Ji X, Wu L, Marion T, Luo Y. Lipid metabolism in regulation of B cell development and autoimmunity. Cytokine Growth Factor Rev 2023; 73:40-51. [PMID: 37419766 DOI: 10.1016/j.cytogfr.2023.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 06/29/2023] [Indexed: 07/09/2023]
Abstract
B cells play an important role in adaptive immunity and participate in the process of humoral immunity mainly by secreting antibodies. The entire development and differentiation process of B cells occurs in multiple microenvironments and is regulated by a variety of environmental factors and immune signals. Differentiation biases or disfunction of B cells participate in the process of many autoimmune diseases. Emerging studies report the impact of altered metabolism in B cell biology, including lipid metabolism. Here, we discuss how extracellular lipid environment and metabolites, membrane lipid-related components, and lipid synthesis and catabolism programs coordinate B cell biology and describe the crosstalk of lipid metabolic programs with signal transduction pathways and transcription factors. We conclude with a summary of therapeutic targets for B cell lipid metabolism and signaling in autoimmune diseases and discuss important future directions.
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Affiliation(s)
- Xing Ji
- Laboratory of Rheumatology and Immunology, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Liang Wu
- Laboratory of Rheumatology and Immunology, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tony Marion
- Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Yubin Luo
- Laboratory of Rheumatology and Immunology, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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13
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Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023; 72:1783-1794. [PMID: 37316169 PMCID: PMC10423489 DOI: 10.1136/gutjnl-2023-329623] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/24/2023] [Indexed: 06/16/2023]
Abstract
SARS-CoV-2 infection may affect the liver in healthy individuals but also influences the course of COVID-19 in patients with chronic liver disease (CLD). As described in healthy individuals, a strong SARS-CoV-2-specific adaptive immune response is important for the outcome of COVID-19, however, knowledge on the adaptive immune response in CLD is limited.Here, we review the clinical and immunological features of SARS-CoV-2 infection in individuals with CLD. Acute liver injury occurs in many cases of SARS-CoV-2 infection and may be induced by multiple factors, such as cytokines, direct viral infection or toxic effects of COVID-19 drugs. In individuals with CLD, SARS-CoV-2 infection may have a more severe course and promote decompensation and particularly in patients with cirrhosis. Compared with healthy individuals, the SARS-CoV-2-specific adaptive immune responses is impaired in patients with CLD after both, natural infection and vaccination but improves at least partially after booster vaccination.Following SARS-CoV-2 vaccination, rare cases of acute vaccine-induced liver injury and the development of autoimmune-like hepatitis have been reported. However, the concomitant elevation of liver enzymes is reversible under steroid treatment.
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Affiliation(s)
- Hendrik Luxenburger
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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14
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Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre NC, Lutz R, Cruz I, Raddassi K, Ruff WE, Racke MK, Wilson JE, Givens TS, Grifoni A, Weiskopf D, Sette A, Kleinstein SH, Montgomery RR, Shaw AC, Li F, Fan R, Hafler DA, Tomayko MM, Longbrake EE. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023; 8:e168102. [PMID: 37606046 PMCID: PMC10543713 DOI: 10.1172/jci.insight.168102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 07/06/2023] [Indexed: 08/23/2023] Open
Abstract
BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
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Affiliation(s)
- Hiromitsu Asashima
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Dongjoo Kim
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA
- Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Kaicheng Wang
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA
| | - Nikhil Lele
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | | | - Rachel Lutz
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Isabella Cruz
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Khadir Raddassi
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | - William E. Ruff
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
- Repertoire Immune Medicines, Cambridge, Massachusetts, USA
| | | | | | | | - Alba Grifoni
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA
| | - Daniela Weiskopf
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA
| | - Alessandro Sette
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA
- Department of Medicine, Division of Infectious Diseases and Global Public Health, UCSD, La Jolla, California, USA
| | - Steven H. Kleinstein
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
- Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA
| | | | - Albert C. Shaw
- Section of Infectious Diseases, Department of Internal Medicine, and
| | - Fangyong Li
- Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA
| | - Rong Fan
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA
- Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
| | - David A. Hafler
- Department of Neurology, and
- Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Mary M. Tomayko
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA
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15
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Lempesis IG, Georgakopoulou VE. Implications of obesity and adiposopathy on respiratory infections; focus on emerging challenges. World J Clin Cases 2023; 11:2925-2933. [PMID: 37215426 PMCID: PMC10198078 DOI: 10.12998/wjcc.v11.i13.2925] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/17/2023] [Accepted: 03/30/2023] [Indexed: 04/25/2023] Open
Abstract
Obesity is characterized by excessive adipose tissue accumulation, which impacts physiological, metabolic, and immune functions. Several respiratory infections, including bacterial pneumonia, influenza, and coronavirus disease 2019, appear to be linked to unfavorable results in individuals with obesity. These may be attributed to the direct mechanical/physiological effects of excess body fat on the lungs’ function. Notably, adipose tissue dysfunction is associated with a low-grade chronic inflammatory status and hyperleptinemia, among other characteristics. These have all been linked to immune system dysfunction and weakened immune responses to these infections. A better understanding and clinical awareness of these risk factors are necessary for better disease outcomes.
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Affiliation(s)
- Ioannis G Lempesis
- Department of Infectious Diseases-COVID-19 Unit, Laiko General Hospital, Athens 11527, Greece
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16
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Johnson R, Ardunay J, Hammond H, Logue J, Jackson L, Baracco L, McGrath M, Dillen C, Patel N, Smith G, Frieman M. Diet Induced Obesity and Diabetes Enhance Mortality and Reduces Vaccine Efficacy for SARS-CoV-2. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2022.10.15.512291. [PMID: 36299426 PMCID: PMC9603822 DOI: 10.1101/2022.10.15.512291] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of October 2022, there have been over 625 million confirmed cases of COVID-19, including over 6.5 million deaths. Epidemiological studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVX-CoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age matched normal mice. Mice fed a high-fat diet (HFD) then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. Depletion of neutrophils in diabetic/obese vaccinated mice reduced disease severity and protected mice from lethality. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study with increasing obesity and diabetes across the world.
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17
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Guo D, Dai J, Ju R, Zhou Q, Wang N, Wu C, Tao H, Jing H, Zhu C, Mao J, Xu J. The relationship between triglyceride, cholesterol and lipoprotein levels, and immune responses to hepatitis B vaccine. Front Med (Lausanne) 2023; 10:1131373. [PMID: 37064020 PMCID: PMC10098103 DOI: 10.3389/fmed.2023.1131373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 03/13/2023] [Indexed: 03/31/2023] Open
Abstract
Cholesterol homeostasis disorder and hypertriglyceridemia, as common metabolic conditions, have rarely been reported to affect the immune responses to the hepatitis B vaccine. Our study found that higher high-density lipoprotein (HDL) level showed a significant relationship with positive anti-HBs results (cOR = 1.479, 95% CI: 1.150, 1.901, p = 0.002; aOR = 1.304, 95% CI: 1.006, 1.691, p = 0.045), especially in individuals aged 18- to 40-year-old, female, smoking more than 100 cigarettes in life, and drinking more than 12 times every year. Lower low-density lipoprotein (LDL) level was associated with a negative anti-HBs result among participants aged 18- to 40-year-old, and participants who were obese. Higher level of HDL and lower level of LDL may be protective factors of better immune effect of hepatitis B vaccine. More research should be conducted to investigate the influence of the cholesterol level on the immune responses to the hepatitis B vaccine, and more in-depth research should be performed to uncover the mechanism.
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Affiliation(s)
- Dan Guo
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Dan Guo,
| | - Jiazhen Dai
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Rong Ju
- Department of Gynaecology and Obstetrics, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Qifan Zhou
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Nenghuan Wang
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Chunhua Wu
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Tao
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Jing
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Chen Zhu
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Jinxian Mao
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Jiayan Xu
- Department of Preventive Health, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
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18
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Ponjoan A, Jacques-Aviñó C, Medina-Perucha L, Romero V, Martí-Lluch R, Alves-Cabratosa L, Ramos R, Berenguera A, Garcia-Gil MDM. Axes of social inequities in COVID-19 clinical trials: A systematic review. Front Public Health 2023; 11:1069357. [PMID: 36891333 PMCID: PMC9987589 DOI: 10.3389/fpubh.2023.1069357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 01/16/2023] [Indexed: 02/16/2023] Open
Abstract
Objective The representativeness of participants is crucial to ensure external validity of clinical trials. We focused on the randomized clinical trials which assessed COVID-19 vaccines to assess the reporting of age, sex, gender identity, race, ethnicity, obesity, sexual orientation, and socioeconomic status in the results (description of the participants' characteristics, loss of follow-up, stratification of efficacy and safety results). Methods We searched the following databases for randomized clinical trials published before 1st February 2022: PubMed, Scopus, Web of Science, and Excerpta Medica. We included peer-reviewed articles written in English or Spanish. Four researchers used the Rayyan platform to filter citations, first reading the title and abstract, and then accessing the full text. Articles were excluded if both reviewers agreed, or if a third reviewer decided to discard them. Results Sixty three articles were included, which assessed 20 different vaccines, mainly in phase 2 or 3. When describing the participants' characteristics, all the studies reported sex or gender, 73.0% race, ethnicity, 68.9% age groups, and 22.2% obesity. Only one article described the age of participants lost to follow-up. Efficacy results were stratified by age in 61.9%, sex or gender in 26.9%, race and/or, ethnicity in 9.5%, and obesity in 4.8% of the articles. Safety results were stratified by age in 41.0%, and by sex or gender in 7.9% of the analysis. Reporting of gender identity, sexual orientation or socioeconomic status of participants was rare. Parity was reached in 49.2% of the studies, and sex-specific outcomes were mentioned in 22.9% of the analysis, most of the latter were related to females' health. Conclusions Axes of social inequity other than age and sex were hardly reported in randomized clinical trials that assessed COVID-19 vaccines. This undermines their representativeness and external validity and sustains health inequities.
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Affiliation(s)
- Anna Ponjoan
- Grup en Salut Vascular de Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Girona, Spain.,Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Spain.,Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Constanza Jacques-Aviñó
- Universitat Autònoma de Barcelona, Bellaterra, Spain.,Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Barcelona, Spain
| | - Laura Medina-Perucha
- Universitat Autònoma de Barcelona, Bellaterra, Spain.,Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Barcelona, Spain
| | - Victor Romero
- Servicio Canario de la Salud, Santa Cruz de Tenerife, Spain
| | - Ruth Martí-Lluch
- Grup en Salut Vascular de Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Girona, Spain.,Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Spain.,Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Lia Alves-Cabratosa
- Grup en Salut Vascular de Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Girona, Spain
| | - Rafel Ramos
- Grup en Salut Vascular de Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Girona, Spain.,Department of Medical Sciences, School of Medicine, Universitat de Girona, Girona, Spain
| | - Anna Berenguera
- Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Barcelona, Spain.,Department of Nursing, Universitat de Girona, Girona, Spain
| | - María Del Mar Garcia-Gil
- Grup en Salut Vascular de Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària (IDIAPJGol), Girona, Spain
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19
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Jalaleddine N, Bouzid A, Hachim M, Sharif-Askari NS, Mahboub B, Senok A, Halwani R, Hamoudi RA, Al Heialy S. ACE2 polymorphisms impact COVID-19 severity in obese patients. Sci Rep 2022; 12:21491. [PMID: 36513710 PMCID: PMC9748040 DOI: 10.1038/s41598-022-26072-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. Accordingly, we hypothesize that obesity-associated ACE2 polymorphisms increase the severity of COVID-19. In this study, we profiled eight frequently reported ACE2 SNPs in a cohort of lean and obese COVID-19 patients (n = 82). We highlight the significant association of rs2285666, rs2048683, rs879922, and rs4240157 with increased severity in obese COVID-19 patients as compared to lean counterparts. These co-morbid-associated SNPs tend to positively correlate, hence proposing possible functional cooperation to ACE2 regulation. In obese COVID-19 patients, rs2285666, rs879922, and rs4240157 are significantly associated with increased blood nitrogen urea and creatinine levels. In conclusion, we highlight the contribution of ACE2 SNPs in enhancing COVID-19 severity in obese individuals. The results from this study provide a basis for further investigations required to shed light on the underlying mechanisms of COVID-19 associated SNPs in COVID-19 obese patients.
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Affiliation(s)
- Nour Jalaleddine
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Amal Bouzid
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
| | - Mahmood Hachim
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | | | - Bassam Mahboub
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
- Department of Pulmonary Medicine and Allergy and Sleep Medicine, Rashid Hospital, Dubai Health Authority, Dubai, UAE
| | - Abiola Senok
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Rabih Halwani
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
- Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE
| | - Rifat A Hamoudi
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
- Division of Surgery and Interventional Science, UCL, London, UK
| | - Saba Al Heialy
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE.
- Meakins-Christie Laboratories,, Research Institute of the McGill University Health Center, Montreal, QC, Canada.
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20
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Hameed M, Geerling E, Pinto AK, Miraj I, Weger-Lucarelli J. Immune response to arbovirus infection in obesity. Front Immunol 2022; 13:968582. [PMID: 36466818 PMCID: PMC9716109 DOI: 10.3389/fimmu.2022.968582] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 11/04/2022] [Indexed: 12/26/2023] Open
Abstract
Obesity is a global health problem that affects 650 million people worldwide and leads to diverse changes in host immunity. Individuals with obesity experience an increase in the size and the number of adipocytes, which function as an endocrine organ and release various adipocytokines such as leptin and adiponectin that exert wide ranging effects on other cells. In individuals with obesity, macrophages account for up to 40% of adipose tissue (AT) cells, three times more than in adipose tissue (10%) of healthy weight individuals and secrete several cytokines and chemokines such as interleukin (IL)-1β, chemokine C-C ligand (CCL)-2, IL-6, CCL5, and tumor necrosis factor (TNF)-α, leading to the development of inflammation. Overall, obesity-derived cytokines strongly affect immune responses and make patients with obesity more prone to severe symptoms than patients with a healthy weight. Several epidemiological studies reported a strong association between obesity and severe arthropod-borne virus (arbovirus) infections such as dengue virus (DENV), chikungunya virus (CHIKV), West Nile virus (WNV), and Sindbis virus (SINV). Recently, experimental investigations found that DENV, WNV, CHIKV and Mayaro virus (MAYV) infections cause worsened disease outcomes in infected diet induced obese (DIO) mice groups compared to infected healthy-weight animals. The mechanisms leading to higher susceptibility to severe infections in individuals with obesity remain unknown, though a better understanding of the causes will help scientists and clinicians develop host directed therapies to treat severe disease. In this review article, we summarize the effects of obesity on the host immune response in the context of arboviral infections. We have outlined that obesity makes the host more susceptible to infectious agents, likely by disrupting the functions of innate and adaptive immune cells. We have also discussed the immune response of DIO mouse models against some important arboviruses such as CHIKV, MAYV, DENV, and WNV. We can speculate that obesity-induced disruption of innate and adaptive immune cell function in arboviral infections ultimately affects the course of arboviral disease. Therefore, further studies are needed to explore the cellular and molecular aspects of immunity that are compromised in obesity during arboviral infections or vaccination, which will be helpful in developing specific therapeutic/prophylactic interventions to prevent immunopathology and disease progression in individuals with obesity.
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Affiliation(s)
- Muddassar Hameed
- Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Elizabeth Geerling
- Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, United States
| | - Amelia K. Pinto
- Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, United States
| | - Iqra Miraj
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - James Weger-Lucarelli
- Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
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21
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Immunogenicity of an mRNA-Based COVID-19 Vaccine among Adolescents with Obesity or Liver Transplants. Vaccines (Basel) 2022; 10:vaccines10111867. [PMID: 36366375 PMCID: PMC9693317 DOI: 10.3390/vaccines10111867] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022] Open
Abstract
There are limited data regarding the immunogenicity of mRNA-based SARS-CoV-2 vaccine BNT162b2 among immunosuppressed or obese adolescents. We evaluated the humoral immune response in adolescents with obesity and adolescent liver transplant recipients (LTRs) after receiving two BNT162b2 doses. Sixty-eight participants (44 males; mean age 14.9 ± 1.7 years), comprising 12 LTRs, 24 obese, and 32 healthy adolescents, were enrolled. Immunogenicity was evaluated by anti-SARS-CoV-2 spike protein immunoassay and surrogate viral neutralization tests (sVNT) against the Delta and Omicron (BA.1) variants. At 27.1 ± 3.2 days after the second dose, the antibody levels were 1476.6 ± 1185.4, 2999.4 ± 1725.9, and 4960.5 ± 2644.1 IU/mL in the LTRs, obese adolescents, and controls, respectively (p < 0.001). Among obese individuals, liver stiffness <5.5 kPa was associated with higher antibody levels. The %inhibition of sVNT was significantly lower for the Omicron than that for the Delta variant. Injection site pain was the most common local adverse event. Nine participants (three obese and six controls) developed COVID-19 at 49 ± 11 days after the second vaccination; four were treated with favipiravir. All infections were mild, and the patients recovered without any consequences. Our study supports the need for the booster regimen in groups with an inferior immunogenic response, including LTRs and obese individuals.
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22
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Di Lello FA, Martínez AP, Flichman DM. Insights into induction of the immune response by the hepatitis B vaccine. World J Gastroenterol 2022; 28:4249-4262. [PMID: 36159002 PMCID: PMC9453777 DOI: 10.3748/wjg.v28.i31.4249] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 05/21/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.
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Affiliation(s)
- Federico Alejandro Di Lello
- Microbiology, Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular, Buenos Aires C1113AAD, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
| | - Alfredo Pedro Martínez
- Virology Section, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Buenos Aires C1431FWO, Argentina
| | - Diego Martín Flichman
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
- Microbiology, Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida, Buenos Aires C1121ABG, Argentina
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23
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Matsuda N, Jwa SC, Tamura S, Suzuki H, Takamura M, Namba A, Kajihara T, Okagaki R, Kamei Y, Ishihara O. Factors associated with an unfavorable clinical course in hospitalized patients with pelvic inflammatory disease: a retrospective cohort study of 117 patients from a Japanese academic institution. BMC Womens Health 2022; 22:348. [PMID: 35978309 PMCID: PMC9387057 DOI: 10.1186/s12905-022-01925-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 08/08/2022] [Indexed: 11/12/2022] Open
Abstract
Background This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID). Methods A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93). Results The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization. Conclusions Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID.
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24
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The metabolic hormone adiponectin affects the correlation between nutritional status and pneumococcal vaccine response in vulnerable indigenous children. PLoS One 2022; 17:e0270736. [PMID: 35862344 PMCID: PMC9302759 DOI: 10.1371/journal.pone.0270736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/15/2022] [Indexed: 11/19/2022] Open
Abstract
Background
Almost 200 million children worldwide are either undernourished or overweight. Only a few studies have addressed the effect of variation in nutritional status on vaccine response. We previously demonstrated an association between stunting and an increased post-vaccination 13-valent pneumococcal conjugate vaccine (PCV13) response. In this prospective study, we assessed to what extent metabolic hormones may be a modifier in the association between nutritional status and PCV13 response.
Methods
Venezuelan children aged 6 weeks to 59 months were vaccinated with a primary series of PCV13. Nutritional status and serum levels of leptin, adiponectin and ghrelin were measured upon vaccination and their combined effect on serum post-vaccination antibody concentrations was assessed by generalized estimating equations multivariable regression analysis.
Results
A total of 210 children were included, of whom 80 were stunted, 81 had a normal weight and 49 were overweight. Overweight children had lower post-vaccination antibody concentrations than normal weight children (regression coefficient -1.15, 95% CI -2.22 –-0.072). Additionally, there was a significant adiponectin-nutritional status interaction. In stunted children, higher adiponectin serum concentrations were associated with lower post-PCV13 antibody concentrations (regression coefficient -0.19, 95% CI -0.24 –-0.14) while the opposite was seen in overweight children (regression coefficient 0.14, 95% CI 0.049–0.22).
Conclusion
Metabolic hormones, in particular adiponectin, may modify the effect of nutritional status on pneumococcal vaccine response. These findings emphasize the importance of further research to better understand the immunometabolic pathways underlying vaccine response and enable a future of optimal personalized vaccination schedules.
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25
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Insights in paediatric virology during the COVID-19 era (Review). MEDICINE INTERNATIONAL 2022; 2:17. [PMID: 36698505 PMCID: PMC9829203 DOI: 10.3892/mi.2022.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/13/2022] [Indexed: 01/28/2023]
Abstract
The present article provides an overview of the key messages of the topics discussed at the '7th Workshop on Paediatric Virology', which was organised virtually on December 20, 2021 by the Institute of Paediatric Virology, located on the Island of Euboea in Greece. The workshop's plenary lectures were on: i) viral pandemics and epidemics in the ancient Mediterranean; ii) the impact of obesity on the outcome of viral infections in children and adolescents; and iii) COVID-19 and artificial intelligence. Despite the scarcity of evidence from fossils and remnants, viruses have been recognised as significant causes of several epidemics in the ancient Mediterranean. Paediatric obesity, a modifiable critical health risk factor, has been shown to impact on the development, progression and severity of viral infections. Thus, the prevention of paediatric obesity should be included in formulating public health policies and decision-making strategies against emerging global viral threats. During the current COVID-19 pandemic, artificial intelligence has been used to facilitate the identification, monitoring and prevention of SARS-CoV-2. In the future, it will play a fundamental role in the surveillance of epidemic-prone infectious diseases, in the repurposing of older therapies and in the design of novel therapeutic agents against viral infections. The collaboration between different medical specialties and other diverse scientific fields, including archaeology, history, epidemiology, nutritional technologies, mathematics, computer technology, engineering, medical law and ethics is essential for the successful management of paediatric viral infections. The current COVID-19 pandemic has underscored this need, which should be further encouraged in modern medical education.
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26
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Clarke M, Mathew SM, Giles LC, Pena AS, Barr IG, Richmond PC, Marshall HS. A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents. Vaccines (Basel) 2022; 10:699. [PMID: 35632458 PMCID: PMC9142924 DOI: 10.3390/vaccines10050699] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 01/27/2023] Open
Abstract
Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.
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Affiliation(s)
- Michelle Clarke
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.); (A.S.P.)
- The Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
| | - Suja M. Mathew
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.); (A.S.P.)
- The Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
| | - Lynne C. Giles
- School of Public Health and The Robinson Research Institute, The University of Adelaide, Adelaide, SA 5005, Australia;
| | - Alexia S. Pena
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.); (A.S.P.)
- The Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
| | - Ian G. Barr
- WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC 3000, Australia;
| | - Peter C. Richmond
- Discipline of Pediatrics, University of Western Australia, Perth, WA 6009, Australia;
- Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute and Perth Children’s Hospital, Perth, WA 6009, Australia
| | - Helen S. Marshall
- Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia; (M.C.); (S.M.M.); (A.S.P.)
- The Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia
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27
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Loosen SH, Jensen BEO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection 2022; 50:1165-1170. [PMID: 35355237 PMCID: PMC8966865 DOI: 10.1007/s15010-022-01784-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 02/04/2022] [Indexed: 12/12/2022]
Abstract
Purpose Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development. Methods We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS. Results Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28–1.65, p < 0.001) and obesity (OR 1.25, 95% CI 1.08–1.44, p = 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients’ age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54–2.13, p < 0.001), female sex (OR 1.33, 95% CI 1.20–1.47, p < 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39–2.00, p < 0.001) and depression (OR 1.27, 95% CI 1.09–1.47, p = < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09–1.95, p = < 0.012) in men were associated with an increased likelihood of developing LCS. Conclusion Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.
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Affiliation(s)
- Sven H Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
| | - Björn-Erik Ole Jensen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Christian Tanislav
- Department of Geriatrics and Neurology, Diakonie Hospital Jung Stilling, Siegen, Germany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
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28
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Clarke M, Goodchild LM, Evans S, Giles LC, Sullivan SG, Barr IG, Lambert S, Marshall H. Body mass index and vaccine responses following influenza vaccination during pregnancy. Vaccine 2021; 39:4864-4870. [PMID: 34266699 DOI: 10.1016/j.vaccine.2021.06.065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/18/2021] [Accepted: 06/23/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Influenza vaccination is recommended by the World Health Organisation for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza infection. Various factors can influence vaccine immunogenicity, with obesity being one factor implicated in varied responses. This study aimed to investigate the impact of body mass index (BMI) on vaccine responses following influenza vaccination during pregnancy. METHODS Pregnant women attending the Women's and Children's Hospital in South Australia during 2014-2016 were invited to participate. Participant's clinical and demographic factors were recorded prior to administration of licensed seasonal influenza vaccination. Blood samples were collected before and one month post-vaccination to measure antibody responses by haemagglutination inhibition (HI) assay. Seroprotection was defined as a post-vaccination HI titre ≥ 1:40. Regression models assessed associations with failure to achieve seroprotective antibodies to H1, H3, and B influenza strains. RESULTS A total of 96 women were enrolled in the study at a median gestation of 22 weeks with a BMI range of 18-49 kg/m2. Paired sera samples were available for 90/96 (94%). Most pregnant women (72/90, 80%) demonstrated seroprotective antibody titres to all three influenza vaccine antigens (A(H1N1)pdm09, A(H3N2), B/Yamagata) following vaccination. Compared with women with BMI < 30 kg/m2, those with high BMI were less likely to fail to achieve seroprotective antibodies, however this was not statistically significant (RR 0.42, 95% CI 0.11-1.68; p = 0.22). A greater proportion of women vaccinated during their second (47/53, 93%) or third trimester (18/25, 72%) demonstrated seroprotection to all three vaccine antigens following vaccination compared with women vaccinated during their first trimester (7/12, 58%). CONCLUSION High BMI did not impair seroprotection levels following influenza vaccination in pregnant women. Gestation at vaccination may be an important consideration for optimising vaccine protection for pregnant women and their newborns. Further assessment of first trimester influenza vaccine responses is warranted.
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Affiliation(s)
- Michelle Clarke
- Women's and Children's Health Network, North Adelaide, SA, Australia; Adelaide Medical School and The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
| | | | - Sue Evans
- Women's and Children's Health Network, North Adelaide, SA, Australia.
| | - Lynne C Giles
- School of Public Health and The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
| | - Sheena G Sullivan
- WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Epidemiology, University of California, Los Angeles, USA.
| | - Ian G Barr
- WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
| | - Stephen Lambert
- Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia.
| | - Helen Marshall
- Women's and Children's Health Network, North Adelaide, SA, Australia; Adelaide Medical School and The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
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Plant stanol esters might optimise the immune response and improve the SARS-CoV-2/COVID-19 vaccine efficacy in overweight and obese subjects. Br J Nutr 2021; 127:1117-1118. [PMID: 34044900 PMCID: PMC8367865 DOI: 10.1017/s0007114521001781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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30
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Kingma JS, Burgers DMT, Monpellier VM, Wiezer MJ, Blussé van Oud-Alblas HJ, Vaughns JD, Sherwin CMT, Knibbe CAJ. Oral drug dosing following bariatric surgery: General concepts and specific dosing advice. Br J Clin Pharmacol 2021; 87:4560-4576. [PMID: 33990981 PMCID: PMC9291886 DOI: 10.1111/bcp.14913] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 04/06/2021] [Accepted: 05/01/2021] [Indexed: 11/30/2022] Open
Abstract
Bariatric or weight‐loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide guidance for dosing of commonly used drugs in this special population. Upon oral drug administration, the time to maximum concentration is often earlier and this concentration may be higher with less consistent effects on trough concentrations and exposure. Additionally, prescription of liquid formulations to bariatric patients is supported by some reports, even though the high sugar load of these suspensions may be of concern. Studies on extended‐release medications result in an unaltered exposure for a substantial number of drugs. Also, studies evaluating the influence of timing after surgery show dynamic absorption profiles. Although for this group specific advice can be proposed for many drugs, we conclude that there is insufficient evidence for general advice for oral drug therapy after bariatric surgery, implying that a risk assessment on a case‐by‐case basis is required for each drug.
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Affiliation(s)
- Jurjen S Kingma
- Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.,Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Desirée M T Burgers
- Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Valerie M Monpellier
- Nederlandse Obesitas Kliniek (Dutch Obesity Clinic), Huis ter Heide, The Netherlands
| | - Marinus J Wiezer
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | | | - Janelle D Vaughns
- Department of Anesthesia and Pain Medicine, Children's National Health System, Washington, DC, USA.,Division of Clinical Pharmacology, Children's National Health System, Washington, DC, USA
| | - Catherine M T Sherwin
- Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children's Hospital, Dayton, Ohio, USA
| | - Catherijne A J Knibbe
- Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.,Division of Systems Biomedicine & Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands
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31
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Moyad MA. Adult preventive vaccines with other synergistic lifestyle options: is it time to add these ancillary benefits to the overall AS management checklist? World J Urol 2021; 40:43-49. [PMID: 33963444 PMCID: PMC8104041 DOI: 10.1007/s00345-021-03709-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 04/19/2021] [Indexed: 10/24/2022] Open
Abstract
PURPOSE To review the potential ancillary cardiovascular and other health impacts of compliance with general adult vaccination series in the prostate cancer active surveillance (AS) population. No previous review has been published in regard to this specific topic. METHODS Literature review of PubMed data up to December 2020 RESULTS: Compliance rates for adult vaccination are in the approximate anemic range of 25-50% with occasional higher rates of specific vaccines in the elderly population including annual influenza and pneumococcal prevention. Herpes zoster (HZ) and numerous other vaccine preventive illnesses are associated with an increased risk of cardiovascular events. Preliminary evidence suggests vaccine compliance could reduce overall morbidity and mortality, and adherence to heart healthy lifestyle changes and parameters could further improve vaccine efficacy and overall wellness. COVID-19 vaccine utilization and research should also continue to reinforce the direct and ancillary benefits of this entire preventive intervention category. CONCLUSIONS Multiple ancillary lifestyle change recommendations could be included in the AS criteria to potentially reduce morbidity and mortality in this population, and perhaps the most unsung intervention is to improve the inadequate rates of general adult vaccination compliance and other heart healthy behavioral changes that impact their efficacy. Heart health, prostate health, and immune system health are closely interlinked.
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Affiliation(s)
- Mark A Moyad
- Department of Urology, University of Michigan Medical Center, Ann Arbor, MI, 48109-5330, USA.
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32
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Vaccination of immune compromised children-an overview for physicians. Eur J Pediatr 2021; 180:2035-2047. [PMID: 33665677 PMCID: PMC8195953 DOI: 10.1007/s00431-021-03997-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 02/09/2021] [Accepted: 02/17/2021] [Indexed: 01/19/2023]
Abstract
Immune compromised children are threatened by a higher risk of infections; some of these are preventable by vaccination. Primary care physicians play a fundamental role in optimising vaccination status. In this narrative review, we present the evidence on vaccine safety and immunogenicity in immune compromised children and discuss in which conditions live-attenuated vaccines can possibly be used. Vaccination schedules differ in some of these conditions, including the use of vaccines with higher antigenic contents (e.g. high-dose hepatitis B vaccine), additional vaccine doses (e.g. 2-dose schedule meningococcal vaccine), more frequent booster doses (e.g. life-long pneumococcal vaccine booster), supplementary vaccines (e.g. meningococcal B vaccine) and use of vaccines beyond the age of usual recommendation (e.g. Haemophilus influenza type b vaccine after 5 years of age). Serological monitoring is a useful tool for customizing vaccination schedule in immune compromised children, confirming adequate vaccine response and documenting seroprotection (especially against measles and varicella). Finally, verification of vaccination status of all household members can prevent them being vector of transmission of an infection to the immune compromised children. Conclusion: Intensified information strategies are needed to improve trust, rectify perceived risks and improve vaccine acceptability; primary physicians can play a critical role in the latter. What is Known: • Physician's awareness is key to success, since it repeatedly correlates with higher vaccination rates What is New: • The vaccination status of immunocompromised children is rarely up-to-date • Knowing the latest vaccine recommendations is challenging, as they differ for each medical condition and change periodically • This review summarises the vaccine recommendations for children with compromised immune systems and highlights how paediatricians play a key role in coordinating their application.
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33
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Seo SH, Jeong IS, Lee EJ. Impact of Obesity on Urinary Tract Infections in Korean Adults: Secondary Data Analysis Using Community-Based Cohort Study. J Korean Acad Nurs 2021; 51:150-161. [PMID: 33993122 DOI: 10.4040/jkan.20228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/19/2021] [Accepted: 02/10/2021] [Indexed: 11/09/2022]
Abstract
PURPOSE This study investigated the incidence of urinary tract infection (UTI) in community-dwelling adults and identified the association between obesity and UTI. METHODS The participants were 4,926 adults aged over 40 years who had no UTIs at the baseline survey of the Korean Genome Epidemiology Study. Obesity was defined according to the cirtieria of Korean Society for the Study of Obesity using body mass index (BMI) data. UTI was defined as those who had self-reported UTI or had either nitrite, or both leukocytes and blood in the urine dipstick test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariate Cox proportional hazards regression analysis to identify the association between the obesity and UTI. RESULTS The incidence proportion of UTI was 5.1%, and the incidence density per 1,000 person-years was 25.5. After controlling general characteristics, people with BMI ≥30.0 kg/m² remained 1.66 times (HR = 1.66, 95% CI = 1.06~2.60; p < .05) more likely to have UTI than those with normal weight. This trend was also present in men or people aged ≥ 60 years. Among women aged ≥ 60 years, people with BMI ≥ 30.0 kg/m² were 1.98 times (HR = 1.98, 95% CI = 1.01~3.86; p < .05) more likely to have UTI than those with normal weight. CONCLUSION The BMI ≥ 30.0 kg/m² is a risk factor of UTIs in Korean adult men over 40 years and women aged ≥ 60 years. It is necessary to emphasize the importance of obesity management to men or women aged ≥ 60 years, specifically.
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Affiliation(s)
- Seung Hee Seo
- Department of Urology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Ihn Sook Jeong
- College of Nursing, Pusan National University, Yangsan, Korea.
| | - Eun Joo Lee
- Department of Nursing, Dong-Eui University, Busan, Korea
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34
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Yang WS, Chang YC, Chang CH, Wu LC, Wang JL, Lin HH. The Association Between Body Mass Index and the Risk of Hospitalization and Mortality due to Infection: A Prospective Cohort Study. Open Forum Infect Dis 2020; 8:ofaa545. [PMID: 33511222 PMCID: PMC7817078 DOI: 10.1093/ofid/ofaa545] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 11/04/2020] [Indexed: 12/24/2022] Open
Abstract
Background We aim to determine whether obesity increases the risk of various infections using a large prospective population-based cohort. Methods A total of 120 864 adults were recruited from the New Taipei City health screening program from 2005 to 2008. Statistics for hospitalization and mortality due to infection were obtained from the National Health Insurance Database and the National Death Registry in Taiwan. Results During a mean follow-up period of 7.61 years, there were 438, 7582, 5298, and 1480 first hospitalizations due to infection in the underweight, normal, overweight, and obese groups, respectively. Obesity significantly increases the risk of hospitalization for intra-abdominal infections (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.00–1.40), including diverticulitis, liver abscess, acute cholecystitis and anal and rectal abscess, reproductive and urinary tract infection (aHR, 1.38; 95% CI, 1.26–1.50), skin and soft tissue infection (aHR, 2.46; 95% CI, 2.15–2.81), osteomyelitis (aHR, 1.70; 95% CI, 1.14–2.54), and necrotizing fasciitis (aHR, 3.54; 95% CI,1.87–6.67), and this relationship is dose-dependent. This study shows that there is a U-shaped association between body mass index (BMI) and hospitalization for lower respiratory tract infection, septicemia, and the summation of all infections and that underweight people are at the greatest risk, followed by obese people. There is a clear negative relationship between BMI and infection-related mortality. Conclusions The pattern that BMI affects the risk of hospitalization and mortality due to infection varies widely across infection sites. It is necessary to tailor preventive and therapeutic measures against different infections in hosts with different BMIs.
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Affiliation(s)
- Wei-Shun Yang
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taipei, Taiwan
| | - Yi-Cheng Chang
- Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Chia-Hsuin Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Li-Chiu Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jiun-Ling Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.,College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsien-Ho Lin
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
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35
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Barbé-Tuana F, Funchal G, Schmitz CRR, Maurmann RM, Bauer ME. The interplay between immunosenescence and age-related diseases. Semin Immunopathol 2020; 42:545-557. [PMID: 32747977 PMCID: PMC7398288 DOI: 10.1007/s00281-020-00806-z] [Citation(s) in RCA: 193] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/06/2020] [Indexed: 02/07/2023]
Abstract
The aging immune system (immunosenescence) has been implicated with increased morbidity and mortality in the elderly. Of note, T cell aging and low-grade inflammation (inflammaging) are implicated with several age-related conditions. The expansion of late-differentiated T cells (CD28−), regulatory T cells, increased serum levels of autoantibodies, and pro-inflammatory cytokines were implicated with morbidities during aging. Features of accelerated immunosenescence can be identified in adults with chronic inflammatory conditions, such as rheumatoid arthritis, and are predictive of poor clinical outcomes. Therefore, there is an interplay between immunosenescence and age-related diseases. In this review, we discuss how the aging immune system may contribute to the development and clinical course of age-related diseases such as neurodegenerative diseases, rheumatoid arthritis, cancer, cardiovascular, and metabolic diseases.
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Affiliation(s)
- Florencia Barbé-Tuana
- Laboratory of Immunobiology, Graduate Program in Cellular and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Giselle Funchal
- Laboratory of Immunobiology, Graduate Program in Cellular and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Carine Raquel Richter Schmitz
- Graduate Program in Cell Biology: Biochemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Rafael Moura Maurmann
- Laboratory of Immunobiology, Graduate Program in Cellular and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Moisés E Bauer
- Laboratory of Immunobiology, Graduate Program in Cellular and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. .,Graduate Program in Biomedical Gerontology, PUCRS, Porto Alegre, Brazil.
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36
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Ramalho R, Rao M, Zhang C, Agrati C, Ippolito G, Wang FS, Zumla A, Maeurer M. Immunometabolism: new insights and lessons from antigen-directed cellular immune responses. Semin Immunopathol 2020; 42:279-313. [PMID: 32519148 PMCID: PMC7282544 DOI: 10.1007/s00281-020-00798-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/02/2020] [Indexed: 02/06/2023]
Abstract
Modulation of immune responses by nutrients is an important area of study in cellular biology and clinical sciences in the context of cancer therapies and anti-pathogen-directed immune responses in health and disease. We review metabolic pathways that influence immune cell function and cellular persistence in chronic infections. We also highlight the role of nutrients in altering the tissue microenvironment with lessons from the tumor microenvironment that shapes the quality and quantity of cellular immune responses. Multiple layers of biological networks, including the nature of nutritional supplements, the genetic background, previous exposures, and gut microbiota status have impact on cellular performance and immune competence against molecularly defined targets. We discuss how immune metabolism determines the differentiation pathway of antigen-specific immune cells and how these insights can be explored to devise better strategies to strengthen anti-pathogen-directed immune responses, while curbing unwanted, non-productive inflammation.
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Affiliation(s)
- Renata Ramalho
- Centro de Investigação Interdisciplinar Egas Moniz (CiiEM, U4585 FCT), Applied Nutrition Studies Group G.E.N.A.-IUEM), Instituto Universitário Egas Moniz, Egas Moniz Higher Education School, Monte de Caparica, Portugal
| | - Martin Rao
- ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal
| | - Chao Zhang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | | | | | - Fu-Sheng Wang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Alimuddin Zumla
- Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK
| | - Markus Maeurer
- ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal.
- I Medizinische Klinik, Johannes Gutenberg University Mainz, Mainz, Germany.
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37
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Garner-Spitzer E, Poellabauer EM, Wagner A, Guzek A, Zwazl I, Seidl-Friedrich C, Binder CJ, Stiasny K, Kundi M, Wiedermann U. Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination. Front Immunol 2020; 11:860. [PMID: 32528467 PMCID: PMC7266951 DOI: 10.3389/fimmu.2020.00860] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/15/2020] [Indexed: 12/21/2022] Open
Abstract
Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon γ levels upon antigen stimulation, indicating a leptin-dependent proinflammatory TH1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned. Clinical Trial Registration: NCT04017052; https://clinicaltrials.gov/ct2/show/NCT04017052.
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Affiliation(s)
- Erika Garner-Spitzer
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Eva-Maria Poellabauer
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Angelika Wagner
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Angela Guzek
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Ines Zwazl
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Claudia Seidl-Friedrich
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
| | - Christoph J Binder
- Department for Laboratory Medicine, Medical University Vienna, Vienna, Austria
| | - Karin Stiasny
- Center of Virology, Medical University Vienna, Vienna, Austria
| | - Michael Kundi
- Center for Public Health, Medical University Vienna, Vienna, Austria
| | - Ursula Wiedermann
- Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
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Gallagher P, Chan KR, Rivino L, Yacoub S. The association of obesity and severe dengue: possible pathophysiological mechanisms. J Infect 2020; 81:10-16. [PMID: 32413364 DOI: 10.1016/j.jinf.2020.04.039] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 04/21/2020] [Accepted: 04/22/2020] [Indexed: 02/06/2023]
Abstract
Dengue virus (DENV) is a medically important flavivirus and the aetiological agent of Dengue, a normally self-resolving febrile illness that, in some individuals, can progress into Severe Dengue (SD), a life-threatening disorder that manifests as organ impairment, bleeding and shock. Many different risk factors have been associated with the development of SD, one of which is obesity. In many countries where DENV is endemic, obesity is becoming more prevalent, therefore SD is becoming an increased public health concern. However, there is a paucity of research on the mechanistic links between obesity and SD. This is a narrative review based on original research and reviews sourced from PubMed and Google Scholar. Four key areas could possibly explain how obesity can promote viral pathogenesis. Firstly, obesity downregulates AMP-Protein Kinase (AMPK), which leads to an accumulation of lipids in the endoplasmic reticulum (ER) that facilitates viral replication. Secondly, the long-term production of pro-inflammatory adipokines found in obese individuals can cause endothelial and platelet dysfunction and can facilitate SD. Thirdly, obesity could also cause endothelial dysfunction in addition to chronic inflammation, through the production of reactive oxygen species (ROS) and possible damage to the glycocalyx found in the endothelium. Finally, obesity has several effects on immunomodulation that reduces NK cell function, B and T cell response and increased pre-disposition to stronger pro-inflammatory cytokine responses after viral infection. Together, these effects can lead to greater viral proliferation and greater tissue damage both of which could contribute to SD. The four mechanisms outlined in this review can be taken as reference starting points for investigating the link between obesity and SD, and to discover potential therapeutic strategies that can potentially reduce disease severity.
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Affiliation(s)
- Peter Gallagher
- University of Warwick, Coventry, UK; Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam
| | | | - Laura Rivino
- Duke-NUS Medical School, Singapore; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Sophie Yacoub
- Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Oxford University, UK.
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Buchy P, Badur S. Who and when to vaccinate against influenza. Int J Infect Dis 2020; 93:375-387. [DOI: 10.1016/j.ijid.2020.02.040] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/19/2020] [Accepted: 02/19/2020] [Indexed: 12/20/2022] Open
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Chan GMF, Fong YF, Ng KL. Tubo-Ovarian Abscesses: Epidemiology and Predictors for Failed Response to Medical Management in an Asian Population. Infect Dis Obstet Gynecol 2019; 2019:4161394. [PMID: 31274977 PMCID: PMC6582870 DOI: 10.1155/2019/4161394] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 04/30/2019] [Accepted: 05/15/2019] [Indexed: 11/30/2022] Open
Abstract
Pelvic inflammatory disease (PID) complicated by tubo-ovarian abscesses (TOA) has long-term sequelae in women of reproductive age. Consensus on the optimal treatment of TOA remains lacking. Most clinicians utilize antibiotics as a first-line conservative approach, failing which invasive intervention is adopted. Our aim is to identify risk factors predicting failed response to conservative medical management for TOA in an Asian population. A retrospective cohort study of 136 patients admitted to a tertiary hospital in Singapore for TOA between July 2013 and December 2017 was performed. Patients were classified into 2 groups: successful medical treatment with intravenous antibiotics and failed medical treatment requiring invasive intervention. 111 (81.6%) of patients were successfully treated with conservative medical approach using intravenous antibiotics; 25 (18.4%) required invasive intervention having failed medical therapy. Multivariate logistic regression model adjusted for age, ethnicity, C-reactive Protein (CRP), TOA size, and body mass index (BMI) showed the odds ratio (OR) of each centimetre increase in TOA size to be 1.28 (95% confidence interval (CI) 1.03-1.61; P=0.030) and every kg/m2 increase in BMI to be 1.10 (95% CI 1.00-1.21; P=0.040). Failed medical management was predicted by a cutoff of TOA size ≥ 7.4 cm and ≥ BMI 24.9 kg/m2. Patients who failed medical treatment received a mean of 4.0±2.1 days of antibiotics before a decision for invasive intervention was made, with a significantly longer intravenous antibiotic duration (9.4±4.3 versus 3.6±2.2 days; P <0.001) and prolonged hospitalization (10.8± 3.6 versus 4.5 ± 2.0 days; P <0.001) compared to the medical group. Patients with higher BMI and larger TOA size were associated with failed response to conservative medical management in our study population. Early identification of these patients for failed medical therapy is imperative for timely invasive intervention to avoid prolonged hospitalization, antibiotic usage, and patient morbidity.
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Affiliation(s)
- Grace Ming Fen Chan
- Department of Obstetrics and Gynaecology, National University Hospital Singapore, Singapore
| | - Yoke Fai Fong
- Department of Obstetrics and Gynaecology, National University Hospital Singapore, Singapore
| | - Kai Lyn Ng
- Department of Obstetrics and Gynaecology, National University Hospital Singapore, Singapore
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Brennan K, O'Leary BD, Mc Laughlin D, Kinlen D, Molloy EJ, Cody D, Paran S, McAuliffe FM, Hogan AE, Doyle SL. Nucleic acid cytokine responses in obese children and infants of obese mothers. Cytokine 2019; 119:152-158. [PMID: 30909151 DOI: 10.1016/j.cyto.2019.03.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 11/27/2022]
Abstract
Almost a third of Irish children are now overweight and the country ranks 58th out of 200 countries for its proportion of overweight youths. With the rising obesity epidemic, and the impaired immune responses of this population, it is vital to understand the effects that obesity has on the immune system and to design future therapeutics, adjuvants and vaccines with overweight and obese populations in mind. Many current vaccines use adjuvants that have been found to be less effective at stimulating the immune response in children compared with adults and there is now substantial effort to design paediatric-focused adjuvants. Additionally, vaccine responses have been shown to be less effective in obese populations indicating that this is a particularly vulnerable population. We have recently identified cytosolic nucleic acids (CNAs), as novel candidate adjuvants for childhood vaccines. Here we investigated whether immune responses to these candidate adjuvants were adversely affected in infants born to overweight or obese mothers, and in overweight and obese children. Type I Interferon (IFN) and proinflammatory cytokines such as Tumor Necrosis Factor α (TNFα) are vital for driving innate and adaptive immune responses. We found that childhood obesity conferred no significant adverse effect on CNA-induced Type I IFN responses when compared with lean children. Similarly, Type I IFN responses were intact in the cord blood of babies delivered from overweight and obese mothers, when compared with lean mothers. There was also no significant impact of obesity on CNA-induced TNFα responses in children or from cord blood of infants born to overweight/obese mothers. In all cases, there was a tendency towards decreased production of innate cytokine Type I Interferon and TNFα, however there was no significant negative correlation. Interestingly, high maternal BMI showed weak and moderate positive correlation with IL-12p70 and IFNγ, respectively, in response to CNA stimulation. This study demonstrates that future adjuvants can be tailored for these populations through the use of activators of CNA sensors.
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Affiliation(s)
- Kiva Brennan
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland
| | - Bobby D O'Leary
- UCD Perinatal Research Centre, Obstetrics & Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Danielle Mc Laughlin
- Department of Paediatric Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland
| | - David Kinlen
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; Department of Diabetes and Endocrinology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland
| | - Eleanor J Molloy
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland; Coombe Women and Infants University Hospital, Dublin 8, Ireland
| | - Declan Cody
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; Department of Diabetes and Endocrinology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland
| | - Sri Paran
- Department of Paediatric Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland
| | - Fionnuala M McAuliffe
- UCD Perinatal Research Centre, Obstetrics & Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Andrew E Hogan
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; Education and Research Centre and Conway Institute, St. Vincent's University Hospital, University College Dublin, Dublin 4, Ireland; Institute of Immunology, Department of Biology, Maynooth University, Maynooth, Co Kildare, Ireland
| | - Sarah L Doyle
- National Children's Research Centre, Crumlin, Dublin 12, Ireland; School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
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Starbæk SMR, Brogaard L, Dawson HD, Smith AD, Heegaard PMH, Larsen LE, Jungersen G, Skovgaard K. Animal Models for Influenza A Virus Infection Incorporating the Involvement of Innate Host Defenses: Enhanced Translational Value of the Porcine Model. ILAR J 2018; 59:323-337. [PMID: 30476076 DOI: 10.1093/ilar/ily009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 06/19/2018] [Indexed: 01/05/2025] Open
Abstract
Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response. Pigs are natural hosts for the same IAV subtypes as humans, they develop clinical disease mirroring human symptoms, they have similar lung anatomy, and their respiratory physiology and immune responses to IAV infection are remarkably similar to what is observed in humans. The pig model shows high face and target validity for human IAV infection, making it suitable for modeling many aspects of influenza, including increased risk of severe disease and impaired vaccine response due to underlying pathologies such as low-grade inflammation. Comparative analysis of proteins involved in viral pattern recognition, interferon responses, and regulation of interferon-stimulated genes reveals a significantly higher degree of similarity between pig, ferret, and human compared with mice. It is concluded that the pig is a promising animal model displaying substantial human translational value with the ability to provide essential insights into IAV infection, pathogenesis, and immunity.
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Affiliation(s)
- Sofie M R Starbæk
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Louise Brogaard
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Harry D Dawson
- Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland
| | - Allen D Smith
- Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland
| | - Peter M H Heegaard
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Lars E Larsen
- National Veterinary Institute, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Gregers Jungersen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Kerstin Skovgaard
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
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The Future of Influenza Vaccines: A Historical and Clinical Perspective. Vaccines (Basel) 2018; 6:vaccines6030058. [PMID: 30200179 PMCID: PMC6160951 DOI: 10.3390/vaccines6030058] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 08/21/2018] [Accepted: 08/27/2018] [Indexed: 12/16/2022] Open
Abstract
For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before. However, vaccines optimal against some infectious diseases, influenza among them, have remained elusive. This review will highlight the challenges that influenza viruses pose for rational vaccine design. In particular, it will consider the clinically beneficial endpoints, beyond complete sterilizing immunity, that have been achieved with vaccines against other infectious diseases, as well as the barriers to achieving similar success against influenza.
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Greydanus DE, Agana M, Kamboj MK, Shebrain S, Soares N, Eke R, Patel DR. Pediatric obesity: Current concepts. Dis Mon 2018; 64:98-156. [DOI: 10.1016/j.disamonth.2017.12.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Principi N, Camilloni B, Esposito S. Influenza immunization policies: Which could be the main reasons for differences among countries? Hum Vaccin Immunother 2017; 14:684-692. [PMID: 29227734 PMCID: PMC5861803 DOI: 10.1080/21645515.2017.1405188] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Despite the availability of effective prophylactic and therapeutic measures, influenza remains one of the most important infectious disease threats to the human population. Every year, seasonal influenza epidemics infect up to 30% of the population; a relevant portion of the ill are hospitalized, and more than a marginal number die. In an attempt to reduce the medical, social and economic burden of influenza, vaccines are recommended by many health authorities worldwide. However, not all countries have a national program for influenza immunization. The main aim of this paper is to list the differences among influenza immunization policies of various countries, highlighting the most important scientific reasons that may have led health authorities to make different decisions. The manuscript highlights that national influenza immunization policies can vary significantly from country to country. These differences arise from insufficient evidence of the relevance of influenza infection from a clinical, social and economic point of view. The lack of precise data on the true frequency and clinical relevance of influenza infection makes it nearly impossible to establish the economic burden of influenza. Moreover, it remains very difficult to evaluate the efficacy of the different influenza vaccines and whether their use is cost-effective considering the various types of people receiving them and the indirect advantages. Disparities among countries will be overcome only when more reliable data regarding all these aspects of influenza infection, particularly those related to the true impact of the disease, are precisely defined.
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Affiliation(s)
- Nicola Principi
- a Emeritus Professor of Pediatrics, Università degli Studi di Milano , Milano , Italy
| | - Barbara Camilloni
- b Department of Experimental Medicine , Università degli Studi di Perugia , Perugia , Italy
| | - Susanna Esposito
- c Pediatric Clinic , Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia , Perugia , Italy
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Abstract
PURPOSE OF THE REVIEW Obesity and type 2 diabetes (T2D) are considered chronic inflammatory diseases. While early publications have reported the implication of innate immune cells such as macrophages to promote systemic inflammation and metabolic dysfunctions, recent publications underline the alterations of the T cell compartment in human obesity and type 2 diabetes. These recent findings are the focus of this review. RECENT FINDINGS In humans, obesity and T2D induce the expansion of proinflammatory T cells such as CD4 Th1, Th17, and CD8 populations, whereas innate T cells such as MAIT and iNKT cells are decreased. These alterations reflect a loss of total T cell homeostasis that may contribute to tissue and systemic inflammation. Whether these changes are adaptive to nutritional variations and/or contribute to the progression of metabolic diseases remains to be clarified. T cell phenotyping may improve obese and/or T2D patient stratification with therapeutic and prognostic implications.
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Affiliation(s)
- Sothea Touch
- INSERM, UMR_S 1166, Team 6 Nutriomics, 75013, Paris, France
- Sorbonne Universités, UPMC University Paris 06, UMR_S 1166, 75005, Paris, France
- ICAN, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, 75013, Paris, France
| | - Karine Clément
- INSERM, UMR_S 1166, Team 6 Nutriomics, 75013, Paris, France
- Sorbonne Universités, UPMC University Paris 06, UMR_S 1166, 75005, Paris, France
- ICAN, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, 75013, Paris, France
- Nutrition, Endocrinology and Cardiology Departments, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013, Paris, France
| | - Sébastien André
- INSERM, UMR_S 1166, Team 6 Nutriomics, 75013, Paris, France.
- Sorbonne Universités, UPMC University Paris 06, UMR_S 1166, 75005, Paris, France.
- ICAN, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, 75013, Paris, France.
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Green WD, Beck MA. Obesity altered T cell metabolism and the response to infection. Curr Opin Immunol 2017; 46:1-7. [PMID: 28359913 PMCID: PMC5554716 DOI: 10.1016/j.coi.2017.03.008] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 02/27/2017] [Accepted: 03/05/2017] [Indexed: 12/16/2022]
Abstract
An epidemic of obesity over the past three decades increases the risk of chronic and infectious diseases for adults and children alike. Within the past few years, obesity has been shown to impair the adaptive immune response to infection through alterations in T cell functioning. Growing evidence suggests that perturbations in T cell metabolism drives this stunted immune response, stemming from nutrient, hormone and adipokine dysregulation in the obese. In this review, recent findings in the fields of obesity and T cell mediated immunity demonstrate a unique relationship between altered mechanisms of T cell metabolic homeostasis and plasticity of adaptive immune responses in the obese setting.
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Affiliation(s)
- William D Green
- Department of Nutrition, University of North Carolina at Chapel Hill, United States
| | - Melinda A Beck
- Department of Nutrition, University of North Carolina at Chapel Hill, United States.
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Liu F, Guo Z, Dong C. Influences of obesity on the immunogenicity of Hepatitis B vaccine. Hum Vaccin Immunother 2017; 13:1014-1017. [PMID: 28059607 DOI: 10.1080/21645515.2016.1274475] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. DATA SOURCES Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015. CONCLUSIONS Obesity was significantly associated with non-response to hepatitis B vaccine immunization. The risk of nonresponsiveness of hepatitis B vaccine among obese people increased with BMI. Moreover, the obesity might lead to an increased risk of HBV vaccine-escape mutations. The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lymphocyte division and proliferation. Therefore, more studies should be performed to analyze the influences of obesity on the immunogenicity of hepatitis B vaccines to improve the immunoprotecive effect of hepatitis B vaccines in future.
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Affiliation(s)
- Fang Liu
- a Suzhou Center for Disease Control and Prevention , Suzhou , China
| | - Zhirong Guo
- b Department of Epidemiology and Statistics , School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University , Suzhou , Jiangsu , China
| | - Chen Dong
- b Department of Epidemiology and Statistics , School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University , Suzhou , Jiangsu , China
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Maciel SS, Feres M, Gonçalves TED, Zimmermann GS, da Silva HDP, Figueiredo LC, Duarte PM. Does obesity influence the subgingival microbiota composition in periodontal health and disease? J Clin Periodontol 2016; 43:1003-1012. [PMID: 27717180 DOI: 10.1111/jcpe.12634] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2016] [Indexed: 01/27/2023]
Abstract
AIM To evaluate whether obesity affects the subgingival microbial composition of patients with periodontal health or chronic periodontitis (CP). MATERIALS AND METHODS Based on periodontal parameters, body mass index and waist-hip ratio, 166 patients were allocated into one of the following groups: Normal weight (NW) patients with periodontal health (n = 44), NW patients with CP (n = 40), obese patients with periodontal health (n = 40) and obese patients with CP (n = 42). Six subgingival biofilm samples per patient were analysed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. RESULTS Obese patients with CP harboured higher levels and/or higher proportions of several periodontal pathogens than those with NW and CP, including Aggregatibacter actinomycetemcomitans, Eubacterium nodatum, Fusobacterium nucleatum ss vincentii, Parvimonas micra, Prevotella intermedia, Tannerella forsythia, Prevotella melaninogenica and Treponema socranskii. The proportions of most of these pathogens, as well Campylobacter rectus and Eikenella corrodens, were more increased in the diseased sites of the obese patients than in those with NW. Furthermore, the healthy sites of the obese patients, presenting or not CP, also exhibited higher proportions of some of the pathogens than patients with NW. CONCLUSIONS Obesity is associated with increased levels and proportions of periodontal pathogens, especially in patients with CP.
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Affiliation(s)
| | - Magda Feres
- Department of Periodontology, Guarulhos University, São Paulo, Brazil
| | | | - Glaucia Santos Zimmermann
- Department of Periodontology, Guarulhos University, São Paulo, Brazil.,Department of Dentistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
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