Neutralizing antibody levels detected early after mRNA-based vaccination do not predict by themselves subsequent breakthrough infections of SARS-CoV-2.

The development of mRNA vaccines represented a significant achievement in response to the global health crisis during the SARS-CoV-2 pandemic. Evaluating vaccine efficacy entails identifying different anti-SARS-CoV-2 antibodies, such as total antibodies against the Receptor Binding Domain (RBD) of the S-protein, or neutralizing antibodies (NAbs). This study utilized an innovative PETIA-based kit to measure NAb, and the investigation aimed to assess whether levels of anti-RBD IgG and NAb uniformly measured 30 days after vaccination could predict individuals at a higher risk of subsequent infection in the months following vaccination. Among a cohort of healthy vaccinated healthcare workers larger than 6,000, 12 mRNA-1273- and 115 BNT162b2-vaccinated individuals contracted infections after the first two doses. The main finding is that neither anti-RBD IgG nor NAb levels measured at day 30 post-vaccination can be used as predictors of breakthrough infections (BI). Therefore, the levels of anti-SARS-CoV-2 antibodies detected shortly after vaccination are not the pivotal factors involved in antiviral protection, and other characteristics must be considered in understanding protection against infection. Furthermore, the levels of anti-RBD and NAbs followed a very similar pattern, with a correlation coefficient of r = 0.96. This robust correlation would justify ceasing the quantification of NAbs, as the information provided by both determinations is highly similar. This optimization would help allocate resources more efficiently and speed up the determination of individuals' humoral immunity status.

IgG anti-RBD levels during 8-month follow-up post-vaccination with BNT162b2 and mRNA-1273 vaccines in healthcare workers: A one-center study.

Introduction: Since the COVID-19 outbreak, specific mRNA-based anti-SARS-CoV-2 vaccines have been developed and distributed worldwide. Because this is the first time that mRNA vaccines have been used, there are several questions regarding their capacity to confer immunity and the durability of the specific anti-SARS-CoV-2 response. Therefore, the objective of this study was to recruit a large cohort of healthcare workers from the Gregorio Marañón Hospital vaccinated with the mRNA-1273 or BNT126b2 vaccines and to follow-up on IgG anti-RBD levels at 8 months post-vaccination. Methods: We recruited 4,970 volunteers and measured IgG anti-RBD antibodies on days 30 and 240 post-vaccination. Results: We observed that both vaccines induced high levels of antibodies on day 30, while a drastic wane was observed on day 240, where mRNA-1273 vaccinated induced higher levels than BNT162b2. Stratifying by vaccine type, age, gender, and comorbidities, we identified that older mRNA-1273-vaccinated volunteers had higher antibody levels than the younger volunteers, contrary to what was observed in the BNT162b2-vaccinated volunteers. Discussion: In conclusion, we observed that mRNA-1273 has a higher capacity to induce a humoral response than BNT162b2 and that age is a factor in the specific response.

Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines.

Vaccination against SARS-CoV-2 has become the main method of reducing mortality and severity of COVID-19. This work aims to study the evolution of the cellular and humoral responses conferred by two mRNA vaccines after two doses against SARS-CoV-2. On days 30 and 240 after the second dose of both vaccines, the anti-S antibodies in plasma were evaluated from 82 volunteers vaccinated with BNT162b2 and 68 vaccinated with mRNA-1273. Peripheral blood was stimulated with peptides encompassing the entire SARS-CoV-2 Spike sequence. IgG Anti-S antibodies (humoral) were quantified on plasma, and inflammatory cytokines (cellular) were measured after stimulation. We observed a higher response (both humoral and cellular) with the mRNA-1273 vaccine. Stratifying by age and gender, differences between vaccines were observed, especially in women under 48 and men over 48 years old. Therefore, this work could help to set up a vaccination strategy that could be applied to confer maximum immunity.

Nosocomial Transmission of SARS-CoV-2 Involving Vaccinated Health Care Workers.

COVID-19 vaccination has proven to be effective at preventing symptomatic disease but there are scarce data to fully understand whether vaccinated individuals can still behave as SARS-CoV-2 transmission vectors. Based on viral genome sequencing and detailed epidemiological interviews, we report a nosocomial transmission event involving two vaccinated health care-workers (HCWs) and four patients, one of them with fatal outcome. Strict transmission control measures, as during the prevaccination period, must be kept between HCWs and HCWs-patients in nosocomial settings. IMPORTANCE COVID-19 vaccination has proven to be effective at preventing symptomatic disease. Although some transmission events involving vaccinated cases have also been reported, scarce information is still available to fully understand whether vaccinated individuals may still behave as vectors in SARS-CoV-2 transmission events. Here, we report a SARS-CoV-2 nosocomial transmission event, supported on whole genome sequencing, in early March 2021 involving two vaccinated HCWs and four patients in our institution. Strict transmission control measures between HCWs and HCWs - patients in nosocomial settings must not be relaxed, and should be kept as strictly as during the prevaccination period.

Application of 3D printing and distributed manufacturing during the first-wave of COVID-19 pandemic. Our experience at a third-level university hospital.

BACKGROUND: 3D printing and distributed manufacturing represent a paradigm shift in the health system that is becoming critical during the COVID-19 pandemic. University hospitals are also taking on the role of manufacturers of custom-made solutions thanks to 3D printing technology. CASE PRESENTATION: We present a monocentric observational case study regarding the distributed manufacturing of three groups of products during the period of the COVID-19 pandemic from 14 March to 10 May 2020: personal protective equipment, ventilatory support, and diagnostic and consumable products. Networking during this period has enabled the delivery of a total of 17,276 units of products manufactured using 3D printing technology. The most manufactured product was the face shields and ear savers, while the one that achieved the greatest clinical impact was the mechanical ventilation adapters and swabs. The products were manufactured by individuals in 57.3% of the cases, and our hospital acted as the main delivery node in a hub with 10 other hospitals. The main advantage of this production model is the fast response to stock needs, being able to adapt almost in real time. CONCLUSIONS: The role of 3D printing in the hospital environment allows the reconciliation of in-house and distributed manufacturing with traditional production, providing custom-made adaptation of the specifications, as well as maximum efficiency in the working and availability of resources, which is of special importance at critical times for health systems such as the current COVID-19 pandemic.

Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines.

TRIAL DESIGN: An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B. METHODS: 67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old. INCLUSION CRITERIA: NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 µg doses (two complete guidelines). The objective of this study was to provide Health workers-staff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix® dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking. RESULTS: The participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix®, administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix®. 57.14% (12 out 21) had a positive response to second dose of Fendrix®. 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix®. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix®. No serious adverse event occurred. CONCLUSIONS: The use of Fendrix®, is a viable vaccine alternative for NHS workers classified as "non-responders". Revaccination of healthy non-responders with Fendrix®, resulted in very high proportions of responders without adverse events. TRIAL REGISTRATION: The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23). FUNDING: GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013-2016 and co-financed by and the European Regional Development Fund (ERDF).

Overlapping of Independent SARS-CoV-2 Nosocomial Transmissions in a Complex Outbreak.

SARS-CoV-2 nosocomial outbreaks in the first COVID-19 wave were likely associated with a shortage of personal protective equipment and scarce indications on control measures. Having covered these limitations, updates on current SARS-CoV-2 nosocomial outbreaks are required. We carried out an in-depth analysis of a 27-day nosocomial outbreak in a gastroenterology ward in our hospital, potentially involving 15 patients and 3 health care workers. Patients had stayed in one of three neighboring rooms in the ward. The severity of the infections in six of the cases and a high fatality rate made the clinicians suspect the possible involvement of a single virulent strain persisting in those rooms. Whole-genome sequencing (WGS) of the strains from 12 patients and 1 health care worker revealed an unexpected complexity. Five different SARS-CoV-2 strains were identified, two infecting a single patient each, ruling out their relationship with the outbreak; the remaining three strains were involved in three independent, overlapping, limited transmission clusters with three, three, and five cases. Whole-genome sequencing was key to understand the complexity of this outbreak. IMPORTANCE We report a complex epidemiological scenario of a nosocomial COVID-19 outbreak in the second wave, based on WGS analysis. Initially, standard epidemiological findings led to the assumption of a homogeneous outbreak caused by a single SARS-CoV-2 strain. The discriminatory power of WGS offered a strikingly different perspective consisting of five introductions of different strains, with only half of them causing secondary cases in three independent overlapping clusters. Our study exemplifies how complex the SARS-CoV-2 transmission in the nosocomial setting during the second COVID-19 wave occurred and leads to extending the analysis of outbreaks beyond the initial epidemiological assumptions.

Absence of IgG antibodies among high-risk contacts of two confirmed cases of Crimean-Congo haemorrhagic fever in the autonomous region of Madrid (Spain).

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed tick-borne disease. In Spain, the disease has emerged as outbreak associated with high-risk exposures. Our goal was to evaluate the prevalence of antibodies against the CCHF virus (CCHFV) in high-risk contacts. A cross-sectional study was conducted. Three hundred eighty-six high-risk contacts were identified comprising family contacts and hospital workers who had attended the cases. Fifty-seven cases with closer exposure were selected. However, forty-nine cases participated in the study. IgG antibodies were detected by immunoenzymatic techniques. All determinations tested negative for anti-CCHFV IgG antibodies. Most of the responders were women (73.5%), and belong to the intensive care department (53.1%). In relation to other possible sources of exposures, 18.4% travelled to countries with CCHF transmission risk. No CCHF positivity was recorded among selected high-risk contacts. This highlights the importance of standard precautions which might have protected healthcare workers and care providers from CCHF infection.

[Treatment of latent tuberculosis among homeless population. Comparison between wo therapeutic approaches]. / Infección tuberculosa latente en población indigente. Comparación de dos pautas terapéuticas.

BACKGROUND AND OBJECTIVE: We aimed to compare treatment adherence and toxicity of isoniazide (H) (6 months) compared with rifampicine (R) + pirazinamide (Z) (2 months) in homeless patients in latent tuberculous infection (LTBI). PATIENTS AND METHOD: Randomized and controlled prospective study. RESULTS: We included 172 patients (116 males and 56 females) with an age average of 42.3 (12.8) years; 31 (18%) had recent conversion and 72 (41.8%) had some risk factor of hepatotoxicity. Both bivariate and multivariate analysis (p < 0.001; OR = 5.15 [2.34-11.35]) showed that the treatment was completed by 61.5% of patients administered the R+Z regimen, while it was completed only by 28.2% of those administered H for 6 months. Moreover, treatment was completed by 48.4% of Spanish or foreign patients with legal residence, while it was completed only by 28.6% of immigrant patients with no legal residence (p = 0.044 in bivariate analysis). CONCLUSIONS: The R+Z regimen for 2 months as treatment of LTBI in homeless patients displays a higher adherence than H for 6 months. There were no differences in toxicity.