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1.
Vaccine X ; 20: 100546, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39221179

RESUMEN

Introduction: Health care workers (HCWs) have been at increased risk of infection during the SARS-CoV-2 pandemic and as essential workers have been prioritised for vaccination. Due to increased exposure HCW are considered a predictor of what might happen in the general population, particularly working age adults. This study aims to summarise effect of vaccination in this 'at risk' cohort. Methods: Ovid MEDLINE and Embase were searched, and 358 individual articles were identified. Of these 49 met the inclusion criteria for review and 14 were included in a meta-analysis. Results: Participants included were predominantly female and working age. Median time to infection was 51 days. Reported vaccine effectiveness against infection, symptomatic infection, and infection requiring hospitalisation were between 5 and 100 %, 34 and 100 %, and 65 and 100 % (respectively). No vaccinated HCW deaths were recorded in any study. Pooled estimates of protection against infection, symptomatic infection, and hospitalisation were, respectively, 84.7 % (95 % CI 72.6-91.5 %, p < 0.0001), 86.0 % (95 % CI 67.2 %-94.0 %; p < 0.0001), and 96.1 % (95 % CI 90.4 %-98.4 %). Waning protection against infection was reported by four studies, although protection against hospitalisation for severe infection persists for at least 6 months post vaccination. Conclusions: Vaccination against SARS-CoV2 in HCWs is protective against infection, symptomatic infection, and hospitalisation. Waning protection is reported but this awaits more mature studies to understand durability more clearly. This study is limited by varying non-pharmacological responses to COVID-19 between included studies, a predominantly female and working age population, and limited information on asymptomatic transmission or long COVID protection.

3.
AIDS ; 38(11): 1722-1724, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088829

RESUMEN

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].


Asunto(s)
Enfermedades Cardiovasculares , Infecciones por VIH , Análisis de la Onda del Pulso , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/administración & dosificación , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Método Doble Ciego , Placebos/administración & dosificación , Adulto , Sulfonamidas/uso terapéutico , Sulfonamidas/farmacología , Resultado del Tratamiento , Pirimidinas , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fluorobencenos/uso terapéutico
4.
J Infect ; 89(4): 106259, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214242

RESUMEN

INTRODUCTION: Following SARS-CoV-2 infection, some patients experience a range of long-lasting symptoms, with a specific burden on their lives and ability to work. AIM: We describe the prevalence and impact of persistent symptoms pre-/post-vaccination in SIREN study participants. METHODS: A cross-sectional study of SARS-CoV-2 positive participants was carried out within SIREN, a frequently tested UK healthcare worker cohort with vaccination and demographic data available. Participants with a SARS-CoV-2 positive PCR or anti-SARS-CoV-2 sample between 01 March 2020 and 31 September 2022 were asked via a questionnaire about symptoms and days absent from work following infection. Responses were excluded if infection dates were inconsistent with study records or missing key data. Symptom type/duration and whether infection occurred pre-/post-vaccination and during which variant period were described. Logistic regression was used to estimate factors associated with persistent symptoms (>12 weeks), adjusting for vaccination and demographic factors. The median days absent from work were also determined. RESULTS: Of 16,599 invitations, 6677 participants responded, and 5053 were included in the analysis. The prevalence of persistent symptoms (symptoms lasting over 12 weeks) differed by infection episode; highest for first infections (32.7%; 1557/4767) compared to second (21.6%; 214/991) and third infections (21.6%; 16/74). Most frequently reported symptoms were fatigue, tiredness, shortness of breath and difficulty concentrating. A higher prevalence of persistent symptoms was reported during the Wild-type variant period compared to the other variant periods (52.9% Wild-type vs. 20.7% Omicron, for any symptom reported during their first infection). Overall, persistent symptoms were higher among unvaccinated participants (unvaccinated 38.1% vs vaccinated 22.0%). Multivariable analysis showed that participants were less likely to report persistent symptoms in infections occurring after vaccination compared to those with an infection before vaccination in the Alpha/Delta and Omicron periods (Alpha/Delta: adjusted Odds Ratio (aOR) 0.66, CI 95% 0.51-0.87, p = aOR 0.07, CI 95% 0.01-0.65, p = 0.02). About half of participants reported that their persistent symptoms impacted their day-to-day (51.8%) and work-related (42.1%) activities 'a little', and 24.0% and 14.4% reported that the impact was 'A lot'. 8.9% reported they had reduced their working hours, and 13.9% had changed their working pattern. DISCUSSION: Persistent symptoms were frequent in our cohort, and there was a reduction in symptom duration in those with multiple infection episodes during later variant periods and post-vaccination. The impact of persistent symptoms resulting in reducing working hours or adjusting working patterns has important implications for workforce resilience. UK healthcare workers were highly exposed during the pandemic, demonstrating a significant burden.

6.
PLoS One ; 19(4): e0299330, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38683799

RESUMEN

An ongoing, severe outbreak of highly pathogenic avian influenza virus (HPAI) A H5N1 clade 2.3.4.4b has been circulating in wild and domestic bird populations throughout the world, reaching North America in 2021. This HPAI outbreak has exhibited unique characteristics when compared to previous outbreaks. The global distribution of disease, prolonged duration, extensive number of species and individual wild birds affected, and the large impact on the global poultry industry have all exceeded historical impacts of previous outbreaks in North America. In this study, we describe the results of HPAI surveillance conducted at The Raptor Center, a wildlife rehabilitation hospital at University of Minnesota (Saint Paul, MN, U.S.A.), from March 28th-December 31, 2022. All wild raptors admitted to the facility were tested for avian influenza viruses using polymerase chain reaction (PCR) testing. All non-negative samples were submitted to the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) National Veterinary Services Laboratories for confirmatory HPAI testing and genetic sequencing. During the study period, 996 individual birds representing 20 different species were tested for avian influenza, and 213 birds were confirmed HPAI positive. Highly pathogenic avian influenza surveillance conducted at The Raptor Center contributed 75% of the HPAI positive raptor detections within the state of Minnesota, located within the Mississippi flyway, significantly augmenting state wildlife surveillance efforts. The viral genotypes observed in birds sampled at The Raptor Center were representative of what was seen in wild bird surveillance within the Mississippi flyway during the same time frame. Wildlife rehabilitation centers provide an opportune situation to augment disease surveillance at the human, wildlife and domestic animal interface during ongoing infectious disease outbreaks.


Asunto(s)
Brotes de Enfermedades , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Rapaces , Animales , Gripe Aviar/epidemiología , Gripe Aviar/virología , Rapaces/virología , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Brotes de Enfermedades/veterinaria , Animales Salvajes/virología , Minnesota/epidemiología , Centros de Rehabilitación
7.
Am J Transplant ; 24(7): 1303-1316, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38499087

RESUMEN

Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) waves, including the impact of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, intensive care unit (ICU) admission, and 30-day and 1-year all-cause mortality. SARS-CoV-2 waves were categorized as Wildtype/Alpha/Delta (318 cases, 16.1%), Omicron BA.1 (268, 26.2%), Omicron BA.2 (268, 13.6%), Omicron BA.5 (561, 28.4%), Omicron BQ.1.1 (188, 9.5%), and Omicron XBB.1.5 (123, 6.2%). Severe COVID-19 rate was highest during the Wildtype/Alpha/Delta wave (44.6%), and lower in Omicron waves (5.7%-16.1%). Lung transplantation was associated with severe COVID-19 (OR: 4.62, 95% CI: 2.71-7.89), along with rituximab treatment (OR: 4.24, 95% CI: 1.04-17.3), long-term corticosteroid use (OR: 3.11, 95% CI: 1.46-6.62), older age (OR: 1.51, 95% CI: 1.30-1.76), chronic lung disease (OR: 2.11, 95% CI: 1.36-3.30), chronic kidney disease (OR: 2.18, 95% CI: 1.17-4.07), and diabetes (OR: 1.97, 95% CI: 1.37-2.83). Early treatment and ≥3 vaccine doses were associated with reduced severity (OR: 0.29, 95% CI: 0.19-0.46, and 0.35, 95% CI: 0.21-0.60, respectively). Tixagevimab/cilgavimab and bivalent boosters did not show a significant impact. The study concludes that COVID-19 severity decreased across different variants in SOTr. Lung transplantation was associated with worse outcomes and may benefit more from preventive and early therapeutic interventions.


Asunto(s)
COVID-19 , Trasplante de Órganos , SARS-CoV-2 , Receptores de Trasplantes , Humanos , COVID-19/epidemiología , Trasplante de Órganos/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Hospitalización/estadística & datos numéricos , Estudios Longitudinales , Unidades de Cuidados Intensivos , Canadá/epidemiología
9.
Biol Psychiatry ; 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38346480

RESUMEN

BACKGROUND: Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic (gamma-aminobutyric acidergic) interneurons (PVINs) within the NAc are required for this process. Perineuronal nets (PNNs) are extracellular matrix structures enriched around PVINs that arise during development and have been proposed to mediate brain circuit stability. However, their function in the adult NAc is largely unknown. Here, we studied the developmental emergence and adult regulation of PNNs in the NAc of male and female mice and examined the cellular and behavioral consequences of reducing the PNN component brevican in NAc PVINs. METHODS: We characterized the expression of PNN components in mouse NAc using immunofluorescence and RNA in situ hybridization. We lowered brevican in NAc PVINs of adult mice using an intersectional viral and genetic method and quantified the effects on synaptic inputs to NAc PVINs and reward-motivated learning. RESULTS: PNNs around NAc PVINs were developmentally regulated and appeared during adolescence. In the adult NAc, PVIN PNNs were also dynamically regulated by cocaine. Transcription of the gene that encodes brevican was regulated in a cell type- and isoform-specific manner in the NAc, with the membrane-tethered form of brevican being highly enriched in PVINs. Lowering brevican in NAc PVINs of adult mice decreased their excitatory inputs and enhanced both short-term novel object recognition and cocaine-induced conditioned place preference. CONCLUSIONS: Regulation of brevican in NAc PVINs of adult mice modulates their excitatory synaptic drive and sets experience thresholds for the development of motivated behaviors driven by rewarding stimuli.

10.
Transpl Infect Dis ; 26(2): e14243, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38407514

RESUMEN

This is a case of a kidney transplant recipient who presented with skin lesions, low-grade fevers, and pancytopenia 2 months after his transplant.


Asunto(s)
Trasplante de Riñón , Humanos , Argentina , Trasplante de Riñón/efectos adversos , América Latina
11.
Transplantation ; 108(5): 1249-1256, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38291585

RESUMEN

BACKGROUND: Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients. METHODS: Using a large, prospective cohort of adult transplant patients with COVID-19, we identified patients with SARS-CoV-2 reinfections. We performed a 1:1 nearest neighbor propensity score matching to control potential confounders, including the COVID-19 variant. We compared outcomes including oxygen requirement, hospitalization, and intensive care unit admission within 30 d after diagnosis between patients with reinfection and those with the first episode of COVID-19. RESULTS: Between 2020 and 2023, 103 reinfections were identified in a cohort of 1869 transplant recipients infected with SARS-CoV-2 (incidence of 2.7% per year). These included 50 kidney (48.5%), 27 lung (26.2%), 7 heart (6.8%), 6 liver (5.8%), and 13 multiorgan (12.6%) transplants. The median age was 54.5 y (interquartile range [IQR], 40.5-65.5) and the median time from transplant to first infection was 6.6 y (IQR, 2.8-11.2). The time between the primary COVID-19 and reinfection was 326 d (IQR, 226-434). Three doses or more of SARS-CoV-2 vaccine are received by 87.4% of patients. After propensity score matching, reinfections were associated with significantly lower hospitalization (5.8% versus 19.4%; risk ratio, 0.3; 95% CI, 0.12-0.71) and oxygen requirement (3.9% versus 13.6%; risk ratio, 0.29; 95% CI, 0.10-0.84). In a within-patient analysis only in the reinfection group, the second infection was milder than the first (3.9% required oxygen versus 19.4%, P < 0.0001), and severe first COVID-19 was the only predictor of severe reinfection. CONCLUSIONS: Transplant recipients with COVID-19 reinfection present better outcomes than those with the first infection, providing clinical evidence for the development of cross-protective immunity.


Asunto(s)
COVID-19 , Trasplante de Órganos , Reinfección , Receptores de Trasplantes , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/prevención & control , Hospitalización/estadística & datos numéricos , Trasplante de Órganos/efectos adversos , Estudios Prospectivos , Reinfección/epidemiología , Factores de Riesgo , Receptores de Trasplantes/estadística & datos numéricos , Resultado del Tratamiento
12.
Vet Pathol ; 61(3): 410-420, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38197395

RESUMEN

An epidemic of highly pathogenic avian influenza (HPAI) began in North America in the winter of 2021. The introduced Eurasian H5N1 clade 2.3.4.4b virus subsequently reassorted with North American avian influenza strains. This postmortem study describes the lesions and influenza A virus antigen distribution in 3 species of raptors, including bald eagles (Haliaeetus leucocephalus, n = 6), red-tailed hawks (Buteo jamaicensis, n = 9), and great horned owls (Bubo virginianus, n = 8), naturally infected with this virus strain based on positive reverse transcriptase polymerase chain reaction and sequencing results from oropharyngeal swabs. The birds presented with severe neurologic signs and either died or were euthanized because of the severity of their clinical signs and suspected influenza virus infection. Gross lesions were uncommon and included forebrain hemorrhages in 2 eagles, myocarditis in 1 hawk, and multifocal pancreatic necrosis in 3 owls. Histological lesions were common and included encephalitis, myocarditis, multifocal pancreas necrosis, multifocal adrenal necrosis, histiocytic splenitis, and anterior uveitis in decreasing frequency. Influenza A viral antigen was detected in brain, heart, pancreas, adrenal gland, kidney, spleen, liver, and eye. In conclusion, bald eagles, red-tailed hawks, and great horned owls infected with the HPAI clade 2.3.4.4b virus strain and showing neurological signs of illness may develop severe or fatal disease with histologically detectable lesions in the brain that are frequently positive for viral antigen.


Asunto(s)
Antígenos Virales , Águilas , Halcones , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Estrigiformes , Animales , Estrigiformes/virología , Águilas/virología , Halcones/virología , Gripe Aviar/virología , Gripe Aviar/patología , Antígenos Virales/análisis , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Masculino , Femenino
13.
Transpl Infect Dis ; 26(1): e14206, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38055610

RESUMEN

In this clinicopathological conference, invited experts discussed a previously published case of a patient with nonischemic cardiomyopathy who underwent heart transplantation from a genetically modified pig source animal. His complex course included detection of porcine cytomegalovirus by plasma microbial cell-free DNA and eventual xenograft failure. The objectives of the session included discussion of selection of immunosuppressive regimens and prophylactic antimicrobials for human xenograft recipients, description of infectious disease risk assessment and mitigation in potential xenograft donors and understanding of screening and therapeutic strategies for potential xenograft-related infections.


Asunto(s)
Trasplante de Corazón , Animales , Humanos , Porcinos , Trasplante Heterólogo/efectos adversos , Trasplante de Corazón/efectos adversos , Inmunosupresores/efectos adversos , Donantes de Tejidos
14.
J Infect ; 88(1): 30-40, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37926119

RESUMEN

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring.


Asunto(s)
Vacuna BNT162 , COVID-19 , Humanos , Estudios de Cohortes , COVID-19/prevención & control , Vacunas contra la COVID-19 , Vacunas de ARNm , Reinfección , SARS-CoV-2 , Reino Unido/epidemiología
15.
Lancet Reg Health Eur ; 36: 100809, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38111727

RESUMEN

Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI -11.4 to 27.8) and 1.7% (95% CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

16.
Open Forum Infect Dis ; 10(11): ofad550, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38023562

RESUMEN

Background: In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods: We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results: In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell-depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions: Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post-breakthrough COVID-19 in vaccinated patients with HM.

17.
Nature ; 623(7985): 132-138, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37853126

RESUMEN

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.


Asunto(s)
COVID-19 , Infección Hospitalaria , Transmisión de Enfermedad Infecciosa , Pacientes Internos , Pandemias , Humanos , Control de Enfermedades Transmisibles , COVID-19/epidemiología , COVID-19/transmisión , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Inglaterra/epidemiología , Hospitales , Pandemias/prevención & control , Pandemias/estadística & datos numéricos , Cuarentena/estadística & datos numéricos , SARS-CoV-2
18.
Open Forum Infect Dis ; 10(10): ofad497, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37869409

RESUMEN

In patients early post-autologous stem cell transplant, seroprotection rates were high for Hemophilus influenzae type B and tetanus toxoid (70%-90%) but lower for Streptococcus pneumoniae (30%-50%) including after revaccination. There were high rates of seropositivity (67%-86%) to measles, mumps, and rubella and varicella zoster virus. Durability of protection requires assessment.

19.
Res Involv Engagem ; 9(1): 97, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853422

RESUMEN

BACKGROUND: Participant involvement in research studies is not a new concept, yet barriers to implementation remain and application varies. This is particularly true for pandemic response research studies, where timeframes are condensed, pressure is high and the value and inclusion of participant involvement can be overlooked. The SIREN Participant Involvement Panel (PIP) provides a case study for participant involvement in pandemic research, working in partnership with people who the research is for and about. METHODS: SIREN and the British Society for Immunology (BSI) recruited and ran two phases of the PIP, involving 15 members in total over a 16-month period. Phase 1 ran between January and August 2022 and Phase 2 between October 2022 and March 2023. Activity figures including recruitment interest and PIP meeting attendance were recorded. To evaluate how the PIP has influenced SIREN, feedback was collected from (a) researchers presenting at the PIP and (b) PIP members themselves. Evaluation at the end of Phase 1 informed our approach to Phase 2. Thematic grouping was planned to identify key lessons learned. RESULTS: Applications increased from n = 30 to n = 485 between Phase 1 and Phase 2 of the PIP, a more than 15-fold increase. The SIREN PIP positively impacted the design, implementation and evaluation phases of the study and sub-studies. Feedback from PIP members themselves was positive, with members highlighting that they found the role rewarding and felt valued. Learnings from the PIP have been condensed into five key themes for applying to future pandemic response research studies: the importance of dedicated resources; recruiting the right panel; understanding motivations for participant involvement; providing flexible options for involvement and enabling the early involvement of participants. CONCLUSIONS: The SIREN PIP has demonstrated the value of actively involving people who research is for and about. The PIP has provided an active feedback mechanism for research and demonstrated a positive influence on both SIREN study researchers and PIP members themselves. This paper makes the case for participant involvement in future pandemic research studies. Future work should include improved training for researchers and we would support the development of a national PIP forum as part of future pandemic research preparedness.


The SARS-Cov2 Immunity & Reinfection Evaluation (SIREN) study was set-up at speed during the early stages of the pandemic to help answer key questions about COVID-19 and inform the national pandemic response. It has provided valuable insight into COVID-19 infections, reinfections, and how well the vaccines work. SIREN helped to find these answers by regularly testing over 44,000 healthcare staff working at 135 NHS organisations. To support participant retention, SIREN established a Participant Involvement Panel (PIP) involving 15 SIREN participants to date. PIP members provide guidance and feedback to SIREN researchers on key research priorities, changes to the study and strategies for maximising participant engagement. This paper provides insight into how the PIP was set-up, run and the resources required from the perspective of the PIP and SIREN researchers. Lessons learned from establishing the PIP are summarised to help inform future pandemic response research studies. The paper adds to the evidence base, and makes the case for, the valuable role participant involvement can play in pandemic response research studies.

20.
J Infect ; 87(5): 420-427, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37689394

RESUMEN

OBJECTIVES: To investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations. METHODS: We performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection. RESULTS: In total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p = 0.02) and Omicron nAbT (p = 0.002). At seven days before infection, controls had higher anti-S levels (p < 0.0001) and nAbT (p < 0.0001; all variants) at matched calendar time. A two-fold increase in anti-S levels was associated with a 29% ([95% CI 14-42%]; p = 0.001) reduction in odds of Delta infection. Delta nAbT>40 were associated with reduced odds of Delta infection (89%, [69-96%]; p < 0.0001), with additional benefits for titres >100 (p = 0.009) and >400 (p = 0.007). CONCLUSIONS: We have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response.


Asunto(s)
Hepatitis D , Vacunas , Humanos , Estudios de Casos y Controles , Anticuerpos Neutralizantes , Vacunación , Anticuerpos Antivirales , Reino Unido/epidemiología
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