Seroprevalencia de anticuerpos frente al SARS-CoV-2 en la Comunidad Valenciana (España) en octubre de 2022 Seroprevalence of antibodies against SARS-CoV-2 in the Valencian Community (Spain) as of October 2022

Objetivo: Estimar la seroprevalencia de anticuerpos frente al SARS-CoV-2 en la Comunidad Valenciana (España) en octubre de 2022, cuando BA.5 era la variante predominante. Método: Estudio transversal de base poblacional de ámbito autonómico en 88 centros de atención primaria de la Comunidad Valenciana seleccionados aleatoriamente. Resultados: La seroprevalencia de anticuerpos antinucleocápside (indicativos de infección previa) y frente al dominio de la unión al receptor (indicativos de infección o vacunación) fue del 71,0% (intervalo de confianza [IC]: 67,8-74,2) y del 98,4% (IC: 97,5-99,3), respectivamente. El 66,7% (IC: 63,4-70,0) de la población mostraba inmunidad híbrida, pero solo el 43,2% de los mayores de 80 años. Conclusiones: La alta proporción de inmunidad híbrida detectada era relevante para las estrategias de salud pública, pero era aconsejable un segundo refuerzo de vacunación en la población anciana.

Seroprevalence of antibodies against SARS-CoV-2 in the Valencian Community (Spain) as of October 2022.

OBJECTIVE: To estimate the seroprevalence of SARS-CoV-2 antibodies in the Valencian Community (Spain) in October 2022, when BA.5 was the predominant variant. METHOD: Cross-sectional, region-wide, population-based serosurvey study in 88 randomly selected primary care centers of the Valencian Community. RESULTS: Seroprevalence of anti-nucleocapsid (indicative of past infection) and total receptor binding domain (indicative of past infection or vaccination) antibodies was 71.0% (confidence interval [CI]: 67.8-74.2) and 98.4% (CI: 97.5-99.3), respectively. 66.7% (CI: 63.4-70.0) of the population shows hybrid immunity, but only 43.2% in those 80 and over. CONCLUSIONS: The high proportion of hybrid immunity detected is relevant for public health strategies. A second vaccination booster was advisable in the elderly population.

A machine learning model for predicting serum neutralizing activity against Omicron SARS-CoV-2 BA.2 and BA.4/5 sublineages in the general population.

Supervised machine learning (ML) methods have been used to predict antibody responses elicited by COVID-19 vaccines in a variety of clinical settings. Here, we explored the reliability of a ML approach to predict the presence of detectable neutralizing antibody responses (NtAb) against Omicron BA.2 and BA.4/5 sublineages in the general population. Anti-SARS-CoV-2 receptor-binding domain (RBD) total antibodies were measured by the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics) in all participants. NtAbs against Omicron BA.2 and BA4/5 were measured using a SARS-CoV-2 S pseudotyped neutralization assay in 100 randomly selected sera. A ML model was built using the variables of age, vaccination (number of doses) and SARS-CoV-2 infection status. The model was trained in a cohort (TC) comprising 931 participants and validated in an external cohort (VC) including 787 individuals. Receiver operating characteristics analysis indicated that an anti-SARS-CoV-2 RBD total antibody threshold of 2300 BAU/mL best discriminated between participants either exhibiting or not detectable Omicron BA.2 and Omicron BA.4/5-Spike targeted NtAb responses (87% and 84% precision, respectively). The ML model correctly classified 88% (793/901) of participants in the TC: 717/749 (95.7%) of those displaying ≥2300 BAU/mL and 76/152 (50%) of those exhibiting antibody levels <2300 BAU/mL. The model performed better in vaccinated participants, either with or without prior SARS-CoV-2 infection. The overall accuracy of the ML model in the VC was comparable. Our ML model, based upon a few easily collected parameters for predicting neutralizing activity against Omicron BA.2 and BA.4/5 (sub)variants circumvents the need to perform not only neutralization assays, but also anti-S serological tests, thus potentially saving costs in the setting of large seroprevalence studies.

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant.

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7-55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, -0.52; p < 0.001) but not in VAC-ex (rho -0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.

Analysis of Healthcare Costs Incurred in Regional Hospitals in Andalusia (Spain) during the COVID-19 Pandemic.

(1) Background: The global health crisis caused by the coronavirus disease (COVID-19) pandemic has led to extreme overloading of different public healthcare systems worldwide. The Spanish Public Healthcare System is one of them. This study aimed to conduct a comparative cost analysis to assess the impact of the COVID-19 pandemic on small- and medium-sized regional hospitals in Andalusia (Spain). (2) Methods: This comparative, multicentre, observational, and retrospective study was designed to perform a comparative cost analysis between the Alto Guadalquivir Health Agency (AGHA) and Poniente University Hospital (PUH), both of which belong to the Spanish Public Health System (PHS). The data included in this study corresponds to the total costs by area and year incurred by the 61,335 patients from both healthcare institutions (AGHA = 36,110; PUH = 25,225) in the areas of hospital emergency service (HES), hospitalisation, and intensive care unit (ICU), during the 24 months of the study period (from 1 January 2019 to 31 December 2020). (3) Results: The analysis results showed a significant increase in costs incurred in 2020 for HES relative to those incurred in 2019 for both AGHA (+14%; p < 0.003) and PUH (+36%; p = 0.002). Additionally, costs incurred for ICU increased significantly in 2020 relative to those incurred in 2019 for both AGHA (+30%; p = 0.003) and PUH (+46%; p = 0.002). Hospitalisation costs for AGHA also increased significantly (+9%; p < 0.012) in 2020 versus those obtained in 2019; however, no significant differences were found for PUH (+6%; p = 1) in the same period analysed. However, the number of patients treated in the areas of HES, hospitalisation, and ICU was significantly reduced throughout 2020 compared to 2019. (4) Conclusions: Our findings show that the costs incurred during 2020 in the regional hospitals of Andalusia (Spain) increased significantly in most of the parameters analysed relative to those incurred in the year before the pandemic (i.e., 2019).

The effectiveness of mRNA vaccines to prevent SARS-CoV-2 infection and hospitalisation for COVID-19 according to the time elapsed since their administration in health professionals in the Valencian Autonomous Community (Spain).

The objective was to understand the effectiveness of the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 in health professionals(HPs) in the Valencian Autonomous Community(Spain) who had completed a full vaccination regimen, both in terms of preventing infections and avoiding hospitalisations, according to the time elapsed since the vaccine administration. Case-controlled study with negative test results. HPs who had undergone at least one PCR or antigen(Ag) active infection diagnostic test(AIDT) to rule out SARS-CoV-2 infection between 25 January and 18 July 2021 were included. HPs with positive AIDT result were considered as cases and those with a negative result controls. Adjusted vaccine effectiveness(VEa) to prevent SARS-CoV-2 infection and its 95% confidence interval(95% CI) were calculated using the formula VEa = (1 - OR) × 100. The VEa for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccine regimen was 91.6%(95%CI[89.6%,93.2%]) for the BNT162b2 vaccine and 95.2%(95%CI[88.3%,98.1%]) for the mRNA-1273 vaccine. After 120 days the VEa was 71.5%(95%CI[67.0%,75.5%]) for the BNT162b2 vaccine and 88.3%(95%CI[75.7,94.4%]) for the mRNA-1273 vaccine. The VEa for prevention of hospitalisation for COVID-19 for the complete two-dose regimen of mRNA vaccines (BNT162b2 and mRNA-1273) was 96.8%(95%CI[76.1%,99.6%]). The administration of the complete regimen of the BNT162b2 and mRNA-1273 vaccine against SARS-CoV-2 was highly effective for the prevention of COVID-19 cases in HPs when 12 to 120 days had elapsed since the second dose. However, said effectiveness decreased as time from the vaccine administration elapsed, although it was maintained for the prevention of hospitalisation of HPs.

Side effects during the week after first dose vaccination with four Covid-19 vaccines. Results of the ProVaVac Survey Study with 13,837 people in Spain.

BACKGROUND: In 2021, four vaccines against Covid-19 (BNT162b2, mRNA-1273, ChAdOx1nCoV-19, and JNJ-78436735) were employed in the region of Valencia, Spain. We conducted a survey to identify real-world, self-reported frequency and severity of side effects during the week after vaccination. METHODS: Survey data was obtained from April 19, 2021, to October 6, 2021, at three different moments in time: day one, day three and day seven after vaccination. Answers were linked to individual-level, personal and clinical information. Respondents were stratified by the vaccine they received and reported effects were presented over time and stratified by severity. We compared our results per vaccine with the frequencies stated in each Summary of Product Characteristics (SmPC). We used binomial logistic models to identify associations between respondent characteristics and side effects. RESULTS: No symptoms were reported by 1,986 respondents (14.35 %), 6,254 informed exclusively mild symptoms (45.20 %), 3,444 up to moderate symptoms (24.89 %), and 2,153 people (15.56 %) notified also severe symptoms. Among the latter, the more frequent were extreme tiredness (7.0 %), and nausea or vomiting (7.1 %). The reported frequency of facial paralysis (0.4 %) was much higher than reflected in SmPCs. Female sex, younger age, previous positive Active Infection Diagnostic Test, chronicity, and vaccination with other than the BNT162b2 vaccine were associated to an increased risk of side effects (p < 0.001). CONCLUSIONS: Side effects after vaccination are common in the real-world. However, they are principally mild, and their frequency declines after a few days. Providing patients with dependable, beforehand information about side effects may improve outcomes and reinforce vaccination programs.

Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.

A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Teledermatology versus Face-to-Face Dermatology: An Analysis of Cost-Effectiveness from Eight Studies from Europe and the United States.

(1) Background: The aim of this systematic review was to compare the cost-effectiveness of two follow-up methods (face-to-face and telemedicine) used in dermatology in the last ten years. (2) Methods: A search for articles that included economic analyses was conducted in August 2021 in the databases PubMed, Medline, Scielo and Scopus using the following keywords: "Cost-Benefit Analysis", "Dermatology", "Telemedicine", "Primary Health Care", as well as other search terms and following the PICOS eligibility criteria. (3) Results: Three clinical trials and five observational studies were analyzed, providing information for approximately 16,539 patients (including four cost-minimization or saving analyses, three cost-effectiveness analyses, and one cost-utility analysis) in Europe and the United States. They describe the follow-up procedures in each of the cases and measure and analyze the direct and indirect costs and effectiveness. All the articles indicate that teledermatology lowers costs and proves satisfactory to both patients and professionals. (4) Conclusions: Although it has been found that follow-up via teledermatology can be more efficient than traditional hospital follow-up, more work is needed to establish evaluation protocols and procedures that measure key variables more equally and demonstrate the quality of the evidence of said studies.

SARS-CoV-2 adaptive immunity in nursing home residents up to eight months after two doses of the Comirnaty® COVID-19 vaccine.

Burgos JS (General Directorate of Research and Healthcare Supervision, Department of Health, Valencia Government, Valencia, Spain); Meneu de Guillerna R (Vice-President Foundation Research Institute in Public Services, Valencia, Spain); Vanaclocha Luna H (General Directorate of Public Health, Department of Health, Valencia Government, Valencia, Spain); Burks DJ (The Prince Felipe Research Center-CIPF-, Valencia, Spain; Cervantes A (INCLIVA Health Research Institute, Valencia, Spain); Comas I (Biomedicine Institute of Valencia, Spanish Research Council (CSIC); Díez-Domingo J (Foundation for the promotion of health and biomedical research of the Valencian Community-FISABIO-, Valencia, Spain); Peiro S (Foundation for the promotion of health and biomedical research of the Valencian Community-FISABIO-, Valencia, Spain); González-Candelas F (CIBER in Epidemiology and Public Health, Spain; Joint Research Unit "Infection and Public Health" FISABIO-University of Valencia, Valencia, Spain; Institute for Integrative Systems Biology (I2SysBio), CSIC-University of Valencia, Valencia, Spain); Ferrer Albiach C (Fundación Hospital Provincial de Castelló); Hernández-Aguado I (University Miguel Hernández, Alicante, Spain); Oliver Ramírez N (DataPop Alliance); Sánchez-Payá J (Preventive Medicine Service, Alicante General and University Hospital, Alicante, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain; Vento Torres M (Instituto de Investigación Sanitaria La Fe); Zapater Latorre E (Fundación Hospital General Universitario de València); Navarro D (Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain;Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain).

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents.

OBJECTIVES: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes. METHODS: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively. RESULTS: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8+ and/or CD4+ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4+ and CD8+ T cells, respectively. DISCUSSION: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents.

Telemedicine in Times of the Pandemic Produced by COVID-19: Implementation of a Teleconsultation Protocol in a Hospital Emergency Department.

Since the first case of COVID-19 was reported in Spain, almost 22% of healthcare professionals have been infected. Among the main causes are exposure during the care of suspected patients and asymptomatic patients, which caused a greater lack of protection in some cases, and to the global shortage of personal protective equipment due to the strong demand for it. The main objective of this study was to evaluate the effectiveness of a teleconsultation protocol with patients who had respiratory symptoms in the reduction of the consumption of personal protective equipment (PPE) in a hospital emergency service (HES) during the COVID-19 pandemic. This is a descriptive and retrospective study that analyzes the implementation of a teleconsultation protocol with patients with respiratory problems treated in the HES at the Hospital de Poniente (Almeria), between 18 March and 30 April 2020. In the selected study period, 5353 patients were treated in the HES of the Hospital de Poniente; of these, 15.43% showed respiratory symptoms and were referred to the Respiratory Circuit, of which 42.2% did so via teleconsultation. Sixty-six cases of COVID-19 were diagnosed, 57.6% were male, and the median age was 71 years old. The main disease related was pneumonia (89.4%), symptoms more frequent were cough (77.3%), fever (77.3%), and dyspnea (60.6%). Lastly, 56.1% of the patients that attended had one or more comorbidities, high blood pressure (53%), and diabetes (36.4%), which became the main risk factors. The results showed that the implementation of teleconsultation in the HES reduced the possibility of infection and allowed for a more efficient consumption of personal protective equipment.