Evolution of anti-SARS-CoV-2 immune response in a cohort of French healthcare workers followed for 7 months.

OBJECTIVES: We aimed to understand the immune response among healthcare workers (HCWs) following SARS-CoV-2 infection, and to determine the infection prevalence during the first wave of the pandemic among workers in our hospital. METHODS: Determination of the serological status against SARS-CoV-2 (nucleocapsid) was offered to all HCWs. All HCWs with positive SARS-CoV-2 serology were proposed to be included in a longitudinal medical and serological follow-up (anti-spike) for 7months. RESULTS: We included 3062 HCWs; 256 (8.4%) were positive for anti-SARS-CoV-2 nucleocapsid IgG. Among them, early decrease in the anti-nucleocapsid antibody index was observed between the first (S1) and second (S2) serology samplings in 208 HCWs (84.2%). The initial anti-nucleocapsid IgG index seemed to be related to the HCWs' age. Seventy-four HCWs were included in the 7-month cohort study. Among them, 69 (90.5%) had detectable anti-spike IgG after 7months and 24 (32.4%) reported persistent symptoms consistent with post-acute COVID-19 syndrome diagnosis. CONCLUSION: The prevalence of serological positivity among HCWs was 6.7%. Infection should be followed by vaccination because of antibody decrease.

Is the second dose of vaccination useful in previously SARS-CoV-2-infected healthcare workers?

Vaccines are the most important public health measure to protect people from COVID-19 worldwide. In addition, healthcare workers account for a large number of infected people. Protecting this population from COVID-19 seems crucial to preserve healthcare systems. In a context of few doses available, serological assays could be useful to decide whether one or two doses are needed. Our results show that a first dose of BNT162b2 mRNA vaccine seems to act as a boost after SARS-CoV-2 infection in healthcare workers with a previous SARS-CoV-2 infection; a second dose might therefore not be required.

Relationship of antibodies to thyrotropin receptors and to thyroid ultrasonographic volume in euthyroid and hypothyroid patients with autoimmune thyroiditis.

It has been reported in hypothyroid patients with Hashimoto's thyroiditis and in patients with primary myxoedema that antibodies (Ab) to the TSH-receptor (R), which inhibit the thyroid gland, decrease both thyroid hormonogenesis and cell growth in vitro. We investigated, in 169 newly diagnosed patients with euthyroid (n = 83) or hypothyroid (n = 86) autoimmune thyroiditis, the relationship between thyroid autoimmunity expression and thyroid ultrasonographic volume or thyroid hormonal status. In patients positive for TSH-receptor (R) antibodies (Ab), negative correlations (P < 0.01) were found between TSH-R Ab levels and free T4 (FT4) values in a euthyroid (r = -0.63), as well as in a hypothyroid (r = -0.54) state, and between TSH-R Ab and total thyroid volume (TTV) values in an euthyroid (r = -0.62) as well as in a hypothyroid (r = -0.53) state. In contrast, no positive correlations were found between TSH levels and FT4 values or TTV levels in patients positive as well as negative for TSH-R Ab in an euthyroid or in a hypothyroid state. These data demonstrate in vivo, that, in contrast to TSH, TSH-R Abs are related to both thyroid hormonal production and volume in euthyroid or hypothyroid patients with autoimmune thyroiditis.

High serum luteinizing hormone levels induce ovarian delta4 cytochrome P450c17alpha down-regulation in hirsute women: complete effect on 17-hydroxylase and partial effect on 17,20-lyase.

It is well known that normal and mildly elevated luteinizing hormone (LH) levels induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha-hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has been shown in both in vitro and in vivo studies in animals and in in vitro studies in women that high LH concentrations have opposite effects on these enzymes. These LH down-regulating effects appear to be more marked on 17,20-lyase than on 17-hydroxylase. Finally, these LH effects have not been reported in vivo in women. Therefore, we investigated the relationships between serum LH levels and serum 17-OHP and androstenedione concentrations in 263 consecutive hirsute women (HW) with normal serum 17-OHP responses to acute adrenocorticotropin (ACTH) stimulation. The patterns of basal serum steroid concentrations differed according to the basal serum LH levels. Indeed, for relationships between LH and 17-OHP concentrations, a positive correlation (P < 0.001) was found between the levels of these parameters when LH levels ranged from 0.2 to 9.0 IU/l. Conversely, for LH levels greater than 9.0 to 21.0 IU/l, LH values were negatively correlated (P<0.001) with 17-OHP concentrations. Similar results were observed for relationships between LH and androstenedione levels but the LH peak level related to decreasing androstenedione concentrations was 12.0 IU/l. Finally, the mean 17-OHP level in patients with LH levels which induced marked P450 down-regulation (i.e. more than 12 IU/l) was similar to that in patients with LH levels within the normal range (i.e. less than 6 IU/l). In contrast, the mean androstenedione level in the former patients was markedly higher (P<0.001) than that in the latter patients. In conclusion, as previously reported in in vitro studies, this in vivo study indicates that LH induces stimulating and down-regulating effects on both ovarian delta(4)17-hydroxylase and delta(4)17,20-lyase activities as serum LH levels gradually increase. However, in contrast to in vitro studies, LH levels which induce P450 down-regulation appear to be less effective on delta(4)17,20-lyase than on delta(4)17-hydroxylase in HW. This strongly suggests that serum factors induce, in most HW, a marked increase in delta(4)17,20-lyase, but not in delta(4)17-hydroxylase, activity leading to both partial impairment of LH-induced delta(4)17,20-lyase down-regulation and complete LH-induced delta(4)17-hydroxylase down-regulation in these patients.

[Contribution of immunoenzymatic technics to the assay of anti-native DNA antibodies in the biological diagnosis of lupus erythematosus disseminatus]. / Apport des techniques immunoenzymatiques au dosage des Ac anti-ADN natif dans le diagnostic biologique du lupus érythémateux disséminé.

Anti native DNA antibodies (anti nDNA Ab), which are a highly specific feature of systemic lupus erythematosus (SLE) were measured by 3 methods: an enzyme linked immunosorbent assay (ELISA), an indirect immunofluorescence test on Crithidia luciliae (IFCL) and the Farr assay (reference test). 114 sera from patients with SLE or another connective tissue disease or without autoimmune rheumatic disease were tested. This study showed that ELISA seemed to be a more sensitive and specific test than IFCL (classical test). ELISA was also as sensitive as the Farr assay. ELISA should replace IFCL for the diagnosis and the follow up of patients with SLE. In other connective tissue diseases, ELISA might give more positive results. Thus these had to be confirmed, especially in the case of low antibodies levels, by using another method (e.g., the Farr assay).

[Brief antiseptic application of iodine in neonatal intensive care units: effects on thyroid function]. / Application brève d'antiseptique iodé en soins intensifs néonatals: conséquences sur la fonction thyroïdienne.

BACKGROUND: Transient thyroid dysfunction with its adverse effects of diminished levels of thyroid hormone on mental development has been reported in neonates whose skin has been cleaned with iodine-containing substances. We report the results of thyroid screening in iodine-exposed neonates and controls. POPULATION AND METHODS: Thirty seven neonates admitted to an intensive care unit from 1990 to 1992 and whose medical condition required umbilical catheterization were included in the study. There were 21 neonates (six term and 15 preterm) for whom the area around the umbilicus was cleansed with iodine antiseptic and 16 controls (four term and 12 preterm) for whom the antiseptic used did not contain iodine. Levels of serum free T3 and T4, and TSH were determined by 7 days after catheterization as did urinary iodine and creatinine concentrations. RESULTS: Iodine-exposed neonates had significant high levels of TSH (P < 0.01) and low free T3 (P < 0.05); levels of free T4 were lower than in controls but not significantly. Urinary iodine excretion was significantly increased. The increase in TSH disappeared between 15 and 30 days after iodine application. CONCLUSION: Application of iodine antiseptics may cause transient thyroid dysfunction in neonates leading to propose the use of non iodinated substances with similar antibacterial efficacy.

Evidence for the effect of antibodies to TSH receptors on the thyroid ultrasonographic volume in patients with Graves' disease.

OBJECTIVE: It has been demonstrated that antibodies (Ab) to thyroid-stimulating hormone receptors (R), which stimulate the thyroid gland, induce hyperthyroidism in patients with Graves' disease. Furthermore, it has been shown in thyroid cells in culture that thyroid-stimulating hormone receptor Ab acts through the adenosine 3', 5'-monophosphate pathway which stimulates both thyroid hormonogenesis and growth. We investigated the relations between thyroid autoimmunity expression and thyroid ultrasonographic parameters or thyroid hormonal status in patients with Graves' disease. PATIENTS: A prospective study of 53 consecutive patients referred with untreated Graves' disease. MEASUREMENTS: Measurements were made of serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab and basal plasma free T4 (FT4), free T3 (FT3) and TSH. Thyroid morphological characteristics (number and total volume of nodule(s), total volume of lobes and total thyroid volume) were determined by ultrasonography. RESULTS: There were significant correlations (P < 0.001) between TSH-RAb levels and FT4 values (r = 0.48) or FT3 levels (r = 0.46). Likewise, significant correlations were found between TSH-RAb levels and total lobe volume values (r = 0.56, P < 0.001), total nodular volume values (r = 0.59, P < 0.01) or total thyroid volume values (r = 0.63, P < 0.001). By contrast, no correlation was found between TSH-RAb levels and the number of nodules or between any of the ultrasonographic parameters and TPOAb levels or TgAB values. CONCLUSIONS: This study demonstrates, in vivo, that TSH receptor antibodies modulate the thyroid ultrasonographic extranodular and nodular volumes in patients with Graves' disease.

Effects of thyroid status on thyroid autoimmunity expression in euthyroid and hypothyroid patients with Hashimoto's thyroiditis.

OBJECTIVE: In patients with hypothyroid goitrous Hashimoto's thyroiditis, the recovery from hypothyroidism seems to be due to a spontaneous decrease of antibodies (Ab) to the TSH-receptor (R). In contrast, in patients with Graves' disease made euthyroid by antithyroid drug therapy, the suppression of TSH secretion by thyroid hormone during antithyroid drug treatment decreases the production of Ab to TSH-R. We investigated in patients with initially euthyroid or hypothyroid goitrous Hashimoto's thyroiditis the relationships between thyroid status and the serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab concentrations in untreated or L-thyroxine (T4) treated patients. PATIENTS: A prospective study of 174 consecutive patients, referred with goitrous Hashimoto's disease in an initially euthyroid (group I, n = 78) or hypothyroid (group II, n = 96) state. The patients with positive (> or = 7%) TSH-RAb (group I, n = 18; group II, n = 22) were reinvestigated 12 months after the initiation of L-T4 therapy. After which, (1) L-T4 was continued and an evaluation performed 2 months later (i.e. 14 months after L-T4 initiation) in 9 patients of group I and in 11 patients of group II or (2) L-T4 was withdrawn and an evaluation performed 2 months later in 9 patients of group I and in 11 patients of group II. MEASUREMENTS: Measurements of basal plasma TSH, free T4 (FT4) and total T3 and serum TSH-R, TPO and TgAb. RESULTS: The prevalence of positive TSH-RAb levels did not differ between group I (23.1%) and group II (22.9%). However, the mean TSH-RAb level in group I (9.4 +/- 0.4%) was lower (P < 0.01) than in group II (11.6 +/- 0.5%). In the patients with positive TSH-R Ab, (1) the prevalences of positive TSH-RAb decreased (P < 0.001) under L-T4 therapy (group I = 22.2%, group II = 21.2%) and increased again (P < 0.01) 2 months after L-T4 cessation (group I = 77.7%, group II = 63.6%) to reach lower levels (group I, P < 0.05; group II, P < 0.01) than those obtained prior to L-T4 treatment. Statistical analysis of TSH levels through the course of the study confirmed these results. (2) In contrast to the variations of the mean TgAb values, the variations of the mean TPOAb levels in each group were in good agreement with those of TSH-RAb through the course of the study. (3) There were significant correlations between some parameters of thyroid status and both TSH-RAb (TSH, r = 0.43, P < 0.001; FT4, r = -0.35, P < 0.01) and TPOAb (TSH, r = 0.42, P < 0.001; FT4, r = -0.31; P < 0.01) levels. In contrast, no correlations were found between thyroid status and TgAb values. CONCLUSIONS: This study demonstrates that thyroid status can modulate thyroid autoimmunity expression, such as TSH-RAb and TPOAb, in patients with euthyroid or hypothyroid goitrous Hashimoto's thyroiditis. Similar results have been reported in patients with Graves' disease made euthyroid by the administration of thyroid hormone during antithyroid drug treatment.