Cellular Immunity of SARS-CoV-2 in the Borriana COVID-19 Cohort: A Nested Case-Control Study.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry-based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

ABO Blood Groups and Incidence of COVID-19 in the Mass Gathering Events in Borriana (Spain), March 2020: A Retrospective Cohort Study.

Our objective was to estimate the incidence of COVID-19 and the ABO blood Groups in the mass-gathering events (MGEs) during the Falles Festival in Borriana (Spain) from 6-10 March 2020. We conducted a population-based retrospective cohort study and measured anti-SARS-CoV-2 antibodies and the ABO of participants. We performed laboratory COVID-19 tests and obtained the ABO in 775 subjects (72.8% of the original exposed cohort): O-group (45.2%), A-group (43.1%), B-group (8.5%) and AB-group (3.4%). Adjusted for confounding factors, including COVID-19 exposure during the MGEs, attack rates of COVID-19 for each ABO group were 55.4%, 59.6%, 60.2%, and 63.7%. The adjusted relative risks were for O-group 0.93 (95% Confidence Interval [CI] 0.83-1.04), for A-group 1.06 (95% CI 0.94-1.18), for B-group 1.04 (95%CI 0.88-1.24), and for AB-group 1.11 (95% CI 0.81-1.51) with no significant differences. Conclusions: Our results suggest no effect of ABO on COVID-19 incidence. We observed weak but not significant protection of the O-group and not a significantly greater infection risk for the remaining groups compared with the O-group. More studies are needed to resolve the controversies regarding the association between ABO and COVID-19.

Incidence, Hospitalization, Mortality and Risk Factors of COVID-19 in Long-Term Care Residential Homes for Patients with Chronic Mental Illness.

Long-term care residential homes (LTCRH) for patients with chronic mental illness have suffered the enormous impact of COVID-19. This study aimed to estimate incidence, hospitalization, mortality, and risk factors of COVID-19 to prevent future epidemics. From March 2020 to January 2021 and before vaccination anti-SARS-CoV-2 begins, cumulate incidence rate (CIR), hospitalization rate (HR), mortality rate (MR), and risk factors of COVID-19 in the 11 LTCRH of two Health Departments of Castellon (Spain) were studied by epidemiological surveillance and an ecological design. Laboratory tests confirmed COVID-19 cases, and multilevel Poisson regression models were employed. All LTCRH participated and comprised 346 residents and 482 staff. Residents had a mean age of 47 years, 40% women, and suffered 75 cases of COVID-19 (CIR = 21.7%), five hospitalizations (HR = 1.4%), and two deaths (MR = 0.6%) with 2.5% fatality-case. Staff suffered 74 cases of the disease (CIR = 15.4%), one hospitalization (HR = 0.2%), and no deaths were reported. Risk factors associated with COVID-19 incidence in residents were private ownership, severe disability, residents be younger, CIR in municipalities where LTCRH was located, CIR in staff, and older age of the facilities. Conclusion: COVID-19 incidence could be prevented by improving infection control in residents and staff and modernizing facilities with increased public ownership.

Incidence, Mortality, and Risk Factors of COVID-19 in Nursing Homes.

During the period from March 2020 to January 2021, we performed an analysis of incidence, mortality, and risk factors of COVID-19 in nursing homes (NHs) in two health departments (HDs) of Castellon (Spain) 2021 through epidemiological surveillance and an ecological design. Laboratory-confirmed COVID-19 cases, cumulative incidence rate (CIR), and mortality rate (MR) of 27 NHs were collected. Information of residents, staff, and facilities was obtained by questionnaire. Multilevel Poisson regression models were applied. All NHs in the HDs participated with 2229 residents (median: 83 years old, 67.3% women) and 1666 staff. Among residents, 815 cases (CIR: 34.8 per 100) and 202 deaths (MR: 8.7 per 100, case fatality 21.0%) were reported and, among staff, 296 cases (CIR: 19.2 per 100) without deaths. Residents' CIR and MR increased with staff CIR, age of the building, residents/staff ratios, occupancy rate, and crowding index; CIR increased with private NH ownership, large NH size, large urban area, and the percentage of women residents; and MR was associated with residents' severe disabilities. In conclusion, several risk factors of COVID-19 incidence and mortality can be prevented by improving infection and quality controls, ameliorating residents/staff ratios, improving structural facilities, and increasing NH public ownership to avoid new outbreaks.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Pulmonary Versus Extrapulmonary Tuberculosis Associated Factors: A Case-Case Study.

BACKGROUND: Tuberculosis (TB) incidence remains low in health departments of Castellon and La Plana-Vila-real, but TB elimination is challenging. The objective of this study was to estimate associated factors of pulmonary tuberculosis (PTB) compared with extrapulmonary tuberculosis (ETB) and investigate epidemiological characteristics of these pathologies to orient control and prevention actions. MATERIALS AND METHODS: A prospective case-case study was implemented by comparing PTB and ETB incidences during 2013-2016 from notification reports, epidemiological surveillance, and microbiological results of hospitals' laboratories Hospital General Castellon and La Plana-Vila-Real in the province of Castellon of Valencia region in Spain. In this design, cases were patients with PTB and controls were patients with ETB. Directed acyclic graph approach was used for selection of potential risk and confounding factors. Adjusted odds ratios (AORs) were estimated by logistic regression models. RESULTS: The study included 136 patients with PTB and 57 patients with ETB, with microbiological confirmation of 93.4% and 52.6%, and the annual median of incidence rates were 7.5 and 3.1 per 100 000 inhabitants, respectively. In general, patients with PTB were younger with higher male proportion than patients with ETB. Risk factors of PTB were smoking tobacco (AOR = 3.98; 95% confidence interval [CI] = 1.66-9.56), social problems (social marginalization, homeless, residence in shelters for the poor, or stay in prison) (AOR = 3.39; 95% CI = 1.05-10.94), and contact with patients with TB (AOR = 2.51; 95% CI = 1.06-5.95). No-smoking tobacco and no-drug abuse interaction decrease PTB risk (AOR = 0.27; 95% CI = 0.12-0.64). From these results, specific measures of health promotion and prevention can be addressed. CONCLUSIONS: The estimated associated factors of PTB may be prevented, and it was demonstrated that the case-case design is useful in the study of TB.

Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study / Comparación de casos esporádicos de Salmonella typhimurium con otros serotipos de Salmonella en Castellón (España): un estudio caso-caso

INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case-case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR = 2.22; 95% CI 1.12-4.43), cold pork meats (OR = 2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection

INTRODUCCIÓN: Las infecciones por Salmonella son frecuentes en España. El objetivo de este estudio fue estimar factores de riesgo y características de las infecciones esporádicas por Salmonella typhimurium (IET), comparadas con infecciones esporádicas por otros serotipos de Salmonella. MÉTODOS: Desde septiembre de 2014 a agosto de 2015 se efectuó un estudio caso-caso por la Sección de Epidemiología del Centro de Salud Pública de Castellón. El caso 1 fueron los pacientes con IET y el caso 2 aquellos con infecciones esporádicas por otros serotipos de Samonella, según los coprocultivos realizados por los laboratorios de Microbiología de los hospitales General de Castellón y La Plana de Vila-real, sin incluir los pacientes de brotes detectados. El serotipo de Salmonella fue identificado en el Centro Nacional de Microbiología (Madrid). RESULTADOS: Se notificaron 327 pacientes con infección por Salmonella, de los que 242 fueron estudiados (74,0%). Ciento cuarenta y ocho pacientes tenían IET y 64, infecciones esporádicas por otros serotipos de Salmonella, con una mediana de edad de 4 y 8,5 años, respectivamente. Los pacientes IET presentaron más episodios diarreicos y sangre en las heces. El consumo de carne de cerdo (OR 2,22; IC 95% 1,12-4,43), fiambres de cerdo (OR 2,49; IC 95% 1,32-4,68) y jugar en la tierra (OR 3,02; IC 95% 1,55-5,88) fueron asociados con IET. En el grupo de 0-4 años, los factores asociados fueron consumo de fiambres de cerdo, tortillas y ser mujer. En el grupo de 5 y más años, solo jugar en la tierra fue asociado con IET. CONCLUSIONES: El consumo de productos porcinos y tortillas, así como jugar en la tierra fueron los factores asociados, y los niños, los más afectados

Comparison of sporadic cases of Salmonella Typhimurium with other Salmonella serotypes in Castellon (Spain): case-case study.

INTRODUCTION: Salmonella infections (SI) are common in Spain. The aim of this study was to appraise risk factors and the clinical characteristics of sporadic Salmonella Typhimurium infections compared with other sporadic salmonella serotype infections (OSI). METHODS: From September 2014 to August 2015, a case-case study was carried out by the Epidemiology Division of the Public Health Centre of Castellon. Case 1 consisted of patients with sporadic S. Typhimurium infections, while case 2 comprised OSI patients, assessed according to the stool cultures analyzed by the Microbiology Laboratories of Hospital General de Castellon and Hospital de La Plana in Vila-real. Patients from detected outbreaks were not included. The salmonella serotype was identified by the National Centre of Microbiology (Madrid). RESULTS: The total number of SI patients reported was 327, 242 of whom were studied (74.0%). 148 patients had sporadic S. Typhimurium infection and 64 had OSI, with median ages of 4 and 8.5 years, respectively. Sporadic S. Typhimurium infection patients presented more blood in feces and diarrhea episodes. Consumption of pork meat (OR=2.22; 95% CI 1.12-4.43), cold pork meats (OR=2.49; 95% CI 1.32-4.68) and playing in the dirt (OR=3.02; 95% CI 1.55-5.88), were associated with sporadic S. Typhimurium infection. In the 0-4 year-old group, the associated factors were consumption of cold pork meats, omelets and female gender. In the 5-year-old and over group, only playing in soil was associated with sporadic S. Typhimurium infection. CONCLUSIONS: The consumption of pork and omelets, as well as playing in the dirt, were the main factors associated with infection. Children were most affected by sporadic S. Typhimurium infection.

Brote de tuberculosis multirresistente en dos colegios de educación secundaria / Outbreak of multidrug-resistant tuberculosis in two secondary schools

Objetivos: Descripción de un brote de tuberculosis multirresistente (TB-MDR) en el medio escolar. Métodos: Se ha realizado un estudio prospectivo y observacional de un brote de TB-MDR en 2 colegios de Onda y de Nules de educación secundaria, en la provincia de Castellón, desde su detección en noviembre de 2008 hasta noviembre de 2014, con seguimiento de los casos y estudio de los contactos. Resultados: Se diagnosticaron 5 casos de TB-MDR, con una tasa global de ataque de la enfermedad del 0,9% y en el estudio de contactos se detectaron 66 con infección latente tuberculosa, con una tasa de infección del 14,4%. Los 5 aislamientos de M. tuberculosis se estudiaron mediante el análisis del polimorfismo de los fragmentos de restricción (RFLP) de la secuencia IS6110 para su caracterización molecular. En los 5 pacientes el cultivo se negativizó a los 4 meses, demostrando la eficacia del tratamiento pautado, sin recaídas hasta la actualidad. Conclusiones: Con la actual globalización y el aumento de la TB-MDR no es extraño la presentación de un brote como el que presentamos y sigue siendo fundamental el estudio de los contactos, el seguimiento estricto de los casos y la disponibilidad de las técnicas de diagnóstico para no demorar el inicio del tratamiento y la quimioprofilaxis, así como la caracterización molecular de las cepas

Objectives: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB) in two schools. Methods: This was a prospective, observational study of an outbreak of MDR-TB in 2 schools located in the towns of Onda and Nules, in the Spanish province of Castellon, from the moment of detection in November 2008 until November 2014, including patient follow-up and contact tracing. Results: Five cases of MDR-TB were diagnosed. Overall attack rate was 0.9%, and among the contacts traced, 66 had latent tuberculous infection, with an infection rate of 14.4%. Molecular characterization of the 5M. tuberculosis isolates was performed by restriction fragment length polymorphism (RFLP) analysis of the IS6110 sequence. In all 5 patients, cultures were negative at 4-month follow-up, showing the efficacy of the treatment given. No recurrence has been reported to date. Conclusions: In the context of globalization and the increased prevalence of MDR-TB, outbreaks such as the one presented here are only to be expected. Contact tracing, strict follow-up of confirmed cases, the availability of fast diagnostic techniques to avoid treatment delay, and chemoprophylaxis, together with the molecular characterization of strains, are still essential

Outbreak of multidrug-resistant tuberculosis in two secondary schools.

OBJECTIVES: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB) in two schools METHODS: This was a prospective, observational study of an outbreak of MDR-TB in 2 schools located in the towns of Onda and Nules, in the Spanish province of Castellon, from the moment of detection in November 2008 until November 2014, including patient follow-up and contact tracing. RESULTS: Five cases of MDR-TB were diagnosed. Overall attack rate was 0.9%, and among the contacts traced, 66 had latent tuberculous infection, with an infection rate of 14.4%. Molecular characterization of the 5M. tuberculosis isolates was performed by restriction fragment length polymorphism (RFLP) analysis of the IS6110 sequence. In all 5 patients, cultures were negative at 4-month follow-up, showing the efficacy of the treatment given. No recurrence has been reported to date. CONCLUSIONS: In the context of globalization and the increased prevalence of MDR-TB, outbreaks such as the one presented here are only to be expected. Contact tracing, strict follow-up of confirmed cases, the availability of fast diagnostic techniques to avoid treatment delay, and chemoprophylaxis, together with the molecular characterization of strains, are still essential.

Reactive arthritis and other musculoskeletal sequelae following an outbreak of Salmonella hadar in Castellon, Spain.

OBJECTIVE: In 2005 a large outbreak of Salmonella hadar occurred in Spain following the consumption of commercial precooked roast chicken. We estimated the incidence and risk factors for reactive arthritis (ReA) and other musculoskeletal sequelae in the patients of this outbreak in 2 health departments of Castellon province. METHODS: A prospective cohort study of the patients and their families was carried out. Clinical infection with Salmonella was considered as the exposure factor. The cohort was studied for ReA symptoms using a telephone questionnaire. Telephone interviews or medical examinations of subjects with musculoskeletal symptoms were conducted by a rheumatologist. Robust Poisson regression models were used in the analysis. RESULTS: From the cohort of 262 people, 248 (94.7%) participated in the telephone survey, 155 with clinical salmonellosis (infected), 78 noninfected, and 15 with some symptoms but not clinical salmonellosis. One hundred one infected patients (65%) reported musculoskeletal symptoms, compared to 19 noninfected (24%) (adjusted relative risk = 2.60, 95% CI 1.73-3.90). Of the infected group, 16 ReA (incidence 10%, 95% CI 6.0-16.2), 7 enthesopathies, and 2 arthralgias were detected, and zero in the noninfected group. The risk factors for ReA were age, weight loss, and duration of diarrhea. Antibiotic treatment for the infection protected against symptoms of peripheral or axial arthritis (adjusted relative risk = 0.73, 95% CI 0.55-0.98). CONCLUSION: The incidence of ReA and musculoskeletal symptoms after the infection was high. The use of antibiotics for S. hadar infection offered some protection against musculoskeletal symptoms.

Varicella vaccine effectiveness during an outbreak in a partially vaccinated population in Spain.

BACKGROUND: An outbreak of varicella occurred between December 2004 and April 2005 in the primary school and day-care center of a town of 5430 inhabitants in Spain. Although the varicella vaccine is not included in the infant vaccination program, some children had been vaccinated before the outbreak. STUDY AIM: The aim of this study was to estimate varicella vaccine effectiveness during an outbreak that took place in a partially vaccinated population of children. METHODS: A cohort study was carried out. Cases were identified through notification by doctors and active search. Information was gathered on the current disease, history of varicella and previous vaccinations together with age, course, school year and other sociodemographic factors. The relative risk (RR) of varicella and the contribution of the previously mentioned factors to the probability of contracting the disease was estimated for vaccinated and unvaccinated children. RESULTS: Participation reached 96.5% (387 of 401 children) in the school and 91.2% (31 of 34 children) in the day-care center. Of 269 children with no history of varicella and with a documented vaccination record, 96 (35.7%) had been previously vaccinated. During the outbreak, 148 cases of varicella were observed. The overall attack rate was 54.4%, 22.9% in vaccinated and 72.8% in unvaccinated children. RR of varicella in vaccinated children was 0.31 (95% confidence interval [CI] = 0.21-0.46). The overall adjusted vaccine effectiveness against varicella was 69.5% (95% CI = 50.5-81.5%) and 96.9% (95% CI = 77.5-99.6%) against mild and severe forms. Only time since vaccination was associated with vaccine failure. CONCLUSIONS: In the varicella outbreak studied, we conclude that vaccine was effective in the prevention of the disease, particularly in its moderate and severe forms, but because the proportion of vaccinated children was low, an outbreak still occurred.