Study of the cellular and humoral immune responses to SARS-CoV-2 vaccination.

Our understanding of cellular immunity in response to COVID-19 infection or vaccination is limited because of less commonly used techniques. We investigated both the cellular and humoral immune responses before and after the administration of a third dose of the SARS-CoV-2 vaccine among a group of healthcare workers. Cellular immunity was evaluated using the VIDAS interferon-gamma (IFNγ) RUO test, which enables automated measurement of IFNγ levels after stimulating peripheral blood lymphocytes. Booster doses significantly enhanced both cellular and humoral immunity. Concerning cellular response, the booster dose increased the percentage of positive IFNγ release assay (IGRA) results but no difference in IFNγ release was found. The cellular response was not associated with protection against SARS-CoV-2 infection. Interestingly, vaccinated and infected healthcare workers exhibited the highest levels of anti-spike and neutralizing antibodies. In conclusion, the IGRA is a simple method for measuring cellular immune responses after vaccination. However, its usefulness as a complement to the study of humoral responses is yet to be demonstrated in future research.

Low performance of interferon gamma release assay Quantiferon-TB gold coupled or not with Pst1/3/lipoglycan humoral detection to predict Mycobacterium tuberculosis complex disease in a low-burden area.

Whole T cell interferon gamma release assays such as QuantiFERON-TB Gold Plus (QTF-TB) are used to evaluate Mycobacterium tuberculosis complex (MTC) exposure but fail to discriminate latent tuberculosis infection (LTBI) from active disease. In this study conducted in a low-burden area, 1215 patients presenting MTC risk and tested both for QTF-TB and mycobacterial infection (microscopy, culture, and/or PCR) were selected, as well as 1298 controls screened with QTF-TB before medical recruitment. The humoral response (LIODetect®TB-ST) was further evaluated in 199 selected patients. In patients with active disease, MTC positivity (culture and/or PCR with species identification) was associated with QTF-TB positivity (45/56, 80.4 %). Although QTF-TB1/TB2 peptides were not suitable for discriminating against active MTC disease from LTBI, the cut-off value of 4.4 IFN-γ IU/mL produced the best diagnostic performance for MTC detection. Lower levels of QTF-TB were reported among patients with isolated active pulmonary MTC as compared to a lymph-nodal location and a disseminated form. Next, antibodies were detected in 4/55 (7.3 %) active MTC disease cases, while negative in cases of LTBI and indeterminate/negative QTF-TB. In conclusion, the added value to combine cellular (QTF-TB) and humoral (LIODetect®TB-ST) assays to predict an active MTC disease is limited.

Antibody Titers and Protection against Omicron (BA.1 and BA.2) SARS-CoV-2 Infection.

The emergence of the SARS-CoV-2 variants of concern has greatly influenced the immune correlates of protection, and there are little data about the antibody threshold concentrations to protect against infection with SARS-CoV-2 Omicron BA.1 or BA.2. We analyzed the antibody responses of 259 vaccinated healthcare workers, some of whom had been previously infected by SARS-CoV-2. The median follow-up was 179 days (IQR: 171-182) after blood collection. We detected 88 SARS-CoV-2 Omicron infections during the follow-up period, 55 (62.5%) with SARS-CoV-2 BA.1, and 33 (37.5%) with SARS-CoV-2 BA.2. A neutralizing antibody titer below 8 provided no protection against a BA.1 infection, a titer of 16 or 32 gave 73.2% protection, and a titer of 64 or 128 provided 78.4% protection. Conversely, the BA.2 infection rate did not vary as a function of anti-BA.2 neutralizing antibody titers. Binding antibody concentrations below 6000 BAU/mL provided no protection against Omicron BA.1 infection, 6000-20,000 BAU/mL provided 55.6% protection, and 20,000 or more provided 87.7% protection. There was no difference in BA.2 infection depending on the binding antibody concentration. Further studies are needed to investigate the relationship between antibody concentrations and infection with the Omicron BA.4/5 variants that are becoming predominant worldwide.

Decreased Efficiency of Neutralizing Antibodies from Previously Infected or Vaccinated Individuals against the B.1.617.2 (Delta) SARS-CoV-2 Variant.

The neutralizing antibody response is a key component of adaptive immunity and a primary protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The increased transmissibility of the SARS-CoV-2 Delta variant and its capacity to cause more severe disease could be linked to a significant reduction in neutralizing antibodies generated during a previous infection or vaccination. We analyzed blood samples from 162 unvaccinated health care workers (HCWs) collected 1 to 3 months postinfection and from 263 vaccinated health care workers 1 month after the last injection. We have compared the neutralizing antibody titers obtained using two virus strains, B.1.160 and B.1.617.2 (Delta variant). Binding antibody concentrations were measured by an immunoassay. The median neutralizing antibody titer against the B.1.160 strain was 128 (interquartile range [IQR], 16 to 256) and 32 (IQR, 8 to 128) against the Delta variant. To obtain a neutralizing antibody titer of 32 or 64, a binding antibody concentration of 182 binding antibody units (BAU)/mL (IQR, 81 to 974) was required with the strain B.1.160, while a concentration of 2,595 BAU/mL (IQR, 1,176 to 5,353) was required with the Delta variant. Our data indicate that antibodies neutralize the SARS-CoV-2 Delta variant 4 times less efficiently than they neutralize an earlier strain. Half of the HCWs had decreased protection from 94% to 76.8% or less for the same total antibody concentration. But neutralization might be correlated with other immune responses. The contributions of other responses, such as those of the T cell and B cell systems, to protection require further investigation. IMPORTANCE Recent studies showed that the neutralizing antibody titer is an important contributor to protection against SARS-CoV-2. With the emergence of new variants, the question arises of maintaining the neutralizing capacities of vaccines and/or of a past infection. We had protective data associated with total antibody concentrations and neutralizing antibody titers for a B.1.160 strain. We showed that to maintain the same levels of protection and, therefore, the same levels of neutralizing antibodies, a total antibody concentration 8.5 times greater is required with the Delta strain. (This study has been registered at ClinicalTrials.gov under registration no. NCT04385108.).

Impact of the treatment of chronic myeloid leukaemia by tyrosine-kinase inhibitors on sick leaves refund: a nationwide cohort study.

BACKGROUND: The advent of chronic myeloid leukaemia (CML) tyrosine-kinase inhibitors (TKI) has led to new paradigms including occupational rehabilitation. OBJECTIVES: This study aimed to characterize the impact of CML treatment on sick leaves within the 2 years following diagnosis in working-age patients. METHODS: A cohort of all 18-60-year-old newly diagnosed CML patients initiating a TKI between January 1st 2011 and December 31st 2014 in France was identified in the French National Healthcare database (Système National des Données de Santé [SNDS]). Patients with a sick leave identified in the 24 months after TKI initiation were compared with sex and initiation date matched controls in a nested case-control design. Factors associated with sick leaves were identified through a conditional logistic regression model, providing adjusted odds-ratio (OR) with their 95% confidence interval (CI). RESULTS: Among 646 18-60-year-old patients, 268 were prescribed at least one sick leave in the study period, with 176 (27.2%) having their first sick leave prescribed after TKI initiation. The median number of sick days over the 2-years period was 115 per patient (interquartile range 25.5-384.5). In the nested case-control study (176 cases and 176 matched controls), sick leaves were more likely observed with second generation TKI (OR 4.11 [1.80-9.38]), whereas they were less likely observed in case if social deprivation (OR 0.07 [0.02-0.28]. CONCLUSION: More than 25% of working-age CML patients had at least one sick leave within 2 years of TKI initiation, with a higher impact of second generation TKI, and with a median duration of 115 days.

The real seroprevalence of SARS-CoV-2 in France and its consequences for virus dynamics.

The SARS-CoV-2 virus has spread world-wide since December 2019, killing more than 2.9 million of people. We have adapted a statistical model from the SIR epidemiological models to predict the spread of SARS-CoV-2 in France. Our model is based on several parameters and assumed a 4.2% seroprevalence in Occitania after the first lockdown. The recent use of serological tests to measure the effective seroprevalence of SARS-CoV-2 in the population of Occitania has led to a seroprevalence around 2.4%. This implies to review the parameters of our model to conclude at a lower than expected virus transmission rate, which may be due to infectivity varying with the patient's symptoms or to a constraint due to an uneven population geographical distribution.

Development of a Questionnaire for the Search for Occupational Causes in Patients with Non-Hodgkin Lymphoma: The RHELYPRO Study.

Non-Hodgkin lymphoma (NHL), multiple myeloma and chronic lymphocytic leukemia are possibly related to environmental and/or occupational exposure. The primary objective of this study was to develop a questionnaire for screening patients with these blood disorders who might benefit from a specialized consultation for possible recognition of the disease as an occupational disease. The study included 205 subjects (male gender, 67.3%; mean age, 60 years; NHL, 78.5%). The questionnaire performed very satisfactorily in identifying the exposures most frequently retained by experts for their potential involvement in the occurrence of NHL. Its sensitivity and specificity in relation to the final expertise were 96% and 96% for trichloroethylene, 85% and 82% for benzene, 78% and 87% for solvents other than trichloroethylene and dichloromethane, 87% and 95% for pesticides, respectively. Overall, 15% of the subjects were invited to ask National Social Insurance for compensation as occupational disease. These declarations concerned exposure to pesticides (64%), solvents (trichloroethylene: 29%; benzene: 18%; other than chlorinated solvents: 18%) and sometimes multiple exposures. In conclusion, this questionnaire appears as a useful tool to identify NHL patients for a specialized consultation, in order to ask for compensation for occupational disease.

[Compensation of damage in cancerology]. / Réparation du dommage en cancérologie.

In a few situations, the consequences secondary to a carcinological pathology require an assessment of damages for compensatory purposes. This is particularly the case when liable parties have been found to be at cause of the disease: occupational pathologies in the case of inexcusable employer's fault, exposure to a radioactive risk, for example in the context of full compensation for damages suffered by the victims of nuclear experiments performed by France, or lastly, in the after-effects of late diagnosis. This article does not discuss the imputability of cancer pathologies to an event, but it proposes an adaptation of methods for assessing damages, in an attempt to provide full compensation for damages.

Evolution of medication consumption in a working environment in France: Results of the four waves of the "Drugs and Work" study (1986-2016).

OBJECTIVES: Previous studies in the working environment have underlined the high prevalence of drug consumption. The aim of this study was to present the main characteristics of this consumption in French workers and to identify changes from the 1986, 1996, 2006 and 2016 surveys. METHODS: The design was a repeated cross-sectional study in 1986, 1996, 2006 and 2016. At each wave, demographic and socio-professional characteristics, self-reported consumption of medications during the week before the occupational medical visit, and perceived difficult working conditions and extraprofessional problems were collected among a sample of workers. Factors associated with consumption of any drug and of main therapeutic classes were investigated through multivariate logistic regression models, using 2016 as the reference for investigating temporal trends. RESULTS: Prevalence of use of any drug was significantly higher in 2016, with marked changes observed in comparison with 1986: absolute decrease of psychotropic (-5.1%, p < 0.0001), antibiotics (-2.7%, p < 0.0001) and cardiovascular drug use (-3.8%, p < 0.0001), increase of analgesic use (+8.3%, p < 0.0001). Difficult working conditions, age and female gender were independently associated with analgesic drug use, and extraprofessional problems and female gender associated with psychotropic drug use. CONCLUSIONS: This analysis of self-reported drug use in the working environment illustrates the global patterns of medication use in a French active population over 3 decades. The favorable development in the level of consumption of psychotropic drugs should not underestimate the attention to be paid to the determinants of chronic consumption, or possible transfers to less stigmatized medications.