Fetal cell microchimerism and susceptibility to COVID-19 disease in women.

PURPOSE: The clinical outcome of COVID-19 disease is worse in males, and the reasons of this gender disparity are currently unclear, though evidences point to a combination of biological and gender-specific factors. A phenomenon unique to the female gender is the fetal cell microchimerism (FCM), defined as the presence of fetal microchimeric cells in maternal organs and in the circulation for years after delivery and usually evaluated by assessing the presence of male cells or DNA in a woman. In the present case-control study, we aimed to evaluate the possible effect of pregnancy and related FCM on the susceptibility to SARS-CoV-2 infection and on the clinical course and outcome of COVID-19. METHODS: One hundred twenty-three women with a previous male pregnancy, comprising 63 COVID-19 cases and 60 healthy controls were enrolled. The presence of blood male DNA was assessed by the amplification of the Y-chromosome specific gene SRY. RESULTS: The prevalence of male DNA of presumed fetal origin was significantly higher in healthy controls than in COVID-19 cases (70 vs 44.4%, P = 0.0044; OR 0.3429, 95% CI 0.1631-0.7207, P = 0.0047). Among women affected with COVID-19, the presence of male FCM did not significantly influence the severity of the disease, though the 8 deceased women studied were all FCM negative. CONCLUSION: This is the first case-control study reporting the prevalence of FCM in COVID-19 and healthy women. Overall, our data seem to suggest a role for FCM in the protection towards the SARS-CoV-2 infection with a possible positive impact on clinical outcome.

Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe.

Introduction: Certain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe. Methods: Serum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory. Results: Median levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769). Discussion: The data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.

Lenvatinib-induced hypocalcaemia due to transient primary hypoparathyroidism.

CONTEXT: Radioiodine refractory differentiated thyroid cancer can be effectively treated with multi-tyrosine-kinase inhibitors (MKIs). Hypocalcaemia has been reported among the side effects of these drugs, but little is known about its pathophysiology and clinical relevance. CASE REPORT: We report the case of a 78-years-old woman with an aggressive papillary thyroid cancer infiltrating perithyroidal structures. The extent of surgery was limited to hemithyroidectomy, RAI treatment could not be performed, and she started lenvatinib treatment. After 4 months of therapy, the patient accessed the Emergency Department for a grade III hypocalcaemia (corrected serum calcium: 6.6 mg/dL, n.v. 8.1-10.4 mg/dL), due to primary hypoparathyroidism (serum PTH: 12.6 ng/L, n.v. 13-64 ng/L). The patient was treated with intravenous calcium infusions and vitamin D supplementation. After discharge, the oral dose of carbonate calcium (CaCO3) was of 6 g/day, and was titrated according to blood exams. Two weeks after discharge, while taking CaCO3 at the dose of 3 g/day, the patient experienced symptomatic grade II hypercalcemia (corrected serum calcium: 11.6 mg/dL), associated to the spontaneous reprise of PTH secretion, and leading to oral calcium withdrawal. During the subsequent follow-up, the patient remained eucalcemic without calcium supplementation. CONCLUSIONS: Though hypocalcaemia has been described as potential side effect of MKI treatment, this is the first report of a lenvatinib-induced primary hypoparathyroidism, in a patient with a documented normal parathyroid function after surgery. The periodical assessment of calcium-phosphorus metabolism is thus warranted to prevent this potentially lethal side effect, in both post-surgical hypoparathyroid and euparathyroid patients.

The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection.

OBJECTIVE: Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. METHODS: We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3-7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. RESULTS: The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. CONCLUSIONS: Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.