Measurement of IFN-γ and IL-2 for the assessment of the cellular immunity against SARS-CoV-2.

The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. The aim of this study was to assess the dual IFN-γ and IL-2 detection, using a SARS-CoV-2 specific fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, and after vaccination. We also evaluated humoral response and compared with T-cells with the aim of correlating both types of responses, and increase the number of specific response detection. Blood samples were drawn from acute COVID-19 patients and convalescent individuals classified according to disease severity; and from unvaccinated and vaccinated uninfected individuals. IgGs against Spike and nucleocapsid, IgMs against nucleocapsid, and neutralizing antibodies were also analyzed. Our results show that IFN-γ in combination with IL-2 increases response detection in acute and convalescent individuals (p = 0.023). In addition, IFN-γ detection can be a useful biomarker for monitoring severe acute patients, as our results indicate that those individuals with a poor outcome have lower levels of this cytokine. In some cases, the lack of cellular immunity is compensated by antibodies, confirming the role of both types of immune responses in infection, and confirming that their dual detection can increase the number of specific response detections. In summary, IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management.

Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Measuring T-Cell Responses against SARS-CoV-2 Is of Utility for Disease and Vaccination Management.

The measurement of specific T-cell responses can be a useful tool for COVID-19 diagnostics and clinical management. In this study, we evaluated the IFN-γ T-cell response against the main SARS-CoV-2 antigens (spike, nucleocapsid and membrane) in acute and convalescent individuals classified according to severity, and in vaccinated and unvaccinated controls. IgG against spike and nucleocapsid were also measured. Spike antigen triggered the highest number of T-cell responses. Acute patients showed a low percentage of positive responses when compared to convalescent (71.6% vs. 91.7%, respectively), but increased during hospitalization and with severity. Some convalescent patients showed an IFN-γ T-cell response more than 200 days after diagnosis. Only half of the vaccinated individuals displayed an IFN-γ T-cell response after the second dose. IgG response was found in a higher percentage of individuals compared to IFN-γ T-cell responses, and moderate correlations between both responses were seen. However, in some acute COVID-19 patients specific T-cell response was detected, but not IgG production. We found that the chances of an IFN-γ T-cell response against SARS-CoV-2 is low during acute phase, but may increase over time, and that only half of the vaccinated individuals had an IFN-γ T-cell response after the second dose.

Follow up of the Humoral Response in Healthcare Workers after the Administration of Two Dose of the Anti SARS-CoV-2 Vaccines-Effectiveness in Delta Variant Breakthrough Infections.

The implementation of vaccination among healthcare workers (HCWs) allowed the management of the pandemic in a manner that differed from that in the first waves. It has been demonstrated that the mRNA vaccines elicit good humoral responses but that there are still breakthrough infections. In summer 2021, a fifth wave emerged, despite the good coverage of HCWs in Spain. We aimed to study the SARS-CoV-2 IgG antibody levels as a marker to predict the possibility of Delta variant infections after vaccination after a seroepidemiological campaign. Of the 5000 participants, a total of 4902 (98.04%) showed a positive result in the serological anti-S test and only 98 (1.96%) were negative. Among the 4368 fully vaccinated participants, only in five cases was the serology negative. Of the total number of participants that received antibody results during the study, 162 were PCR positive in the subsequent two months. Among these, 151 were fully vaccinated (two doses). Significant differences between antibody BAU/mL levels were found between PCR positive and non-PCR positive participants (p < 0.01). The median of BAU/mL was higher in those vaccinated patients with no infection (1260 BAU/mL; 465−2080) versus infected patients (661 BAU/mL; 361−2080). These data support the idea that vaccines play an important role in the control of the pandemic, especially among HCWs at the time of the Delta variant circulation. More studies with other variants of concern must be performed in order to establish a correlation between the levels of IgG and the new infections.

Seroprevalence of SARS-CoV-2 IgG specific antibodies among healthcare workers in the Northern Metropolitan Area of Barcelona, Spain, after the first pandemic wave.

BACKGROUND: The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world has caused a global pandemic, infecting millions of individuals, with an unprecedented impact in health care systems worldwide. Healthcare workers are one of the risk groups that need to be well protected, due to their strategic role in patient management, presently and in prevention of healthcare needs for future outbreaks. Here, we present the results of the first SARS-CoV-2 seroprevalence study in the Northern Metropolitan Area of Barcelona, Spain. METHODS: IgG SARS-CoV-2 antibodies were analyzed in serum samples from 7563 healthcare workers of the Northern Metropolitan Area of Barcelona. Samples were collected after the first pandemic wave (from May 4th to May 22nd, 2020) and were analyzed by automated chemiluminescence assays. All samples were tested for IgG anti-S1/S2. Participant samples with negative or equivocal results but with analytical signals above the limit of detection and/or previously confirmed COVID-19 diagnosis were also tested for IgG anti-Nucleocapsid. RESULTS: A total of 779 of 7563 (10.3%) healthcare workers were positive for anti-SARS-CoV-2 IgG (specific for either S1/S2 or N antigens). No significant differences were observed between those working at primary care or at the reference hospital. Interestingly, among 341 participants with a confirmed COVID-19 diagnosis, 36 (10.55%) tested negative for SARS-CoV-2 IgG (both S1/S2 and recombinant N antigen). CONCLUSION: Seroprevalence of anti-SARS-CoV-2 IgG in the healthcare workers of the North Metropolitan Area of Barcelona was higher than in the general population in the same geographical area. Safety measures have to be stressed in order to protect these essential workers from future pandemic waves.

Serial testing of health care workers for tuberculosis infection: A prospective cohort study.

Health Care Workers (HCW) may have an occupational risk of latent tuberculosis infection (LTBI) and TB disease. The objective of this study was to evaluate the performance of the 2-step strategy: tuberculin skin test (TST) followed by confirmation with Interferon (IFN)-γ- release assays (IGRAs) in HCW. A secondary objective was to determine the factors related to conversions and reversions. HCW at risk of occupational exposure who attended the Occupational Department of the Hospital Germans Trias i Pujol were included during the study period (2013-2016). All professionals testing negative for LTBI were included in a cohort study. These workers were followed up with the administration of a TST and an IGRA quantification at least one year after inclusion in the study. Workers with positive TST, regardless of the results of the IGRA tests, were followed-up with an IGRA. 255 workers were enrolled in the study and 108 workers from the same cohort were followed up. During the follow-up period, seven workers presented TST test conversion. One of these conversions was also confirmed by an IGRA test. There were 2 conversions of cases only testing positive with the IGRA. There have been only 2 reversions of cases testing negative with the IGRA. In this study, not all TST conversions were confirmed when using the IGRA test, which highlights the importance of the 2-step strategy. We have detected a low number of conversions and reversions. Our conclusions should be confirmed in studies with a longer follow-up time.

Guía para la prevención y control de la tuberculosis en el personal sanitario / Guidelines for the prevention and control of tuberculosis in health care workers

La tuberculosis continúa siendo una de las enfermedades transmisibles causantes de mayor morbimortalidad en el mundo. España con una tasa de incidencia de 13,04 por 100.000 habitantes ocupa el tercer lugar entre los países europeos más afectados. Estos datos muestran una tendencia a su disminución, pudiendo pasar desapercibida y hacer que no se realicen las medidas de prevención adecuadas ante un enfermo sospechoso. El personal sanitario que trabaja en un centro donde se atiende a pacientes con tuberculosis presenta riesgo de transmisión, siendo este riesgo superior en determinadas áreas o unidades de trabajo. Desde los Servicios de Prevención de Riesgos Laborales, encargados de vigilar la salud de los trabajadores sanitarios, se elaboran diferentes estrategias de abordaje con el objetivo de evitar la infección en estos trabajadores y detectar la infección tuberculosa reciente. Las guías nacionales existentes hasta la actualidad incluyen la prueba de la tuberculina como prueba de cribado de la infección tuberculosa, con referencia a las nuevas pruebas diagnósticas basadas en la detección in vitro de interferón-gamma (IGRA) para determinados casos. El objetivo de la presente guía ha sido consensuar y establecer unos criterios comunes para incluir las pruebas IGRA, como una ayuda complementaria a la prueba de la tuberculina en el personal sanitario, a partir de la evidencia disponible en la actualidad. Las recomendaciones de su utilización se han adaptado a las diferentes situaciones en que se pueden encontrar los profesionales que participan en la vigilancia de la salud de los trabajadores sanitarios (AU)

Tuberculosis remains one of the communicable diseases that cause increased morbidity and mortality worldwide. With an incidence rate of 13,04 per 100,000 population, Spain ranks third among the most affected European countries. These data show a tendency to decrease meaning that it may go unnoticed with the potential to miss the appropriate preventive measures in a suspected case. In centers where patients are treated with tuberculosis, health care worker presents risk of transmission. This risk is higher in some areas or work units. The Occupational health physicians’ services, which monitorize the health of health care workers, use different strategies in order to prevent and detect tuberculosis infection. The national guidelines include the tuberculin skin test as a screening test for tuberculosis infection with mention of new diagnostic tests based on the in vitro detection of gamma interferon (IGRA) for certain cases. The purpose of this guide is to establish common criteria for IGRA tests, as a supplementary aid to the tuberculin skin test in health care workers, from the evidence available today. Recommendations for its use have been adapted to the different situations faced by the professionals involved in monitoring the health of health workers (AU)

[Guidelines for the prevention and control of tuberculosis in health care workers]. / Guía para la prevención y control de la tuberculosis en el personal sanitario.

Tuberculosis remains one of the communicable diseases that cause increased morbidity and mortality worldwide. With an incidence rate of 13,04 per 100,000 population, Spain ranks third among the most affected European countries. These data show a tendency to decrease meaning that it may go unnoticed with the potential to miss the appropriate preventive measures in a suspected case. In centers where patients are treated with tuberculosis, health care worker presents risk of transmission. This risk is higher in some areas or work units. The Occupational health physicians' services, which monitorize the health of health care workers, use different strategies in order to prevent and detect tuberculosis infection. The national guidelines include the tuberculin skin test as a screening test for tuberculosis infection with mention of new diagnostic tests based on the in vitro detection of gamma interferon (IGRA) for certain cases. The purpose of this guide is to establish common criteria for IGRA tests, as a supplementary aid to the tuberculin skin test in health care workers, from the evidence available today. Recommendations for its use have been adapted to the different situations faced by the professionals involved in monitoring the health of health workers.