Thyroid function before, during and after COVID-19

Context: The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective: We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted upon recovery from COVID-19. Design: Cohort observational study. Participants and setting: Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK with suspected COVID-19 between March 9 to April 22, 2020 were included, excluding those with pre-existing thyroid disease and those missing either free thyroxine (FT4) or TSH measurements. Of 456 patients, 334 had COVID-19 and 122 did not. Main Outcome Measures: TSH and FT4 measurements at admission, and where available, those taken in 2019 and at COVID-19 follow-up. Results: Most patients (86·6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n=185 for TSH and 104 for FT4), both TSH and FT4 were reduced at admission compared to baseline. In a complete cases analysis of COVID-19 patients with TSH measurements at follow-up, admission and baseline (n=55), TSH was seen to recover to baseline at follow-up. Conclusions: Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a non-thyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline

Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

Contains fulltext : 97604.pdf (publisher's version ) (Open Access)BACKGROUND: Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. RESULTS: We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. CONCLUSIONS: Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion

Contributions of Mamu-A*01 Status and TRIM5 Allele Expression, But Not CCL3L Copy Number Variation, to the Control of SIVmac251 Replication in Indian-Origin Rhesus Monkeys

CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis

CCL3L1 Copy Number Variation and Susceptibility to HIV-1 Infection: A Meta-Analysis

Background: Although several studies have investigated whether CCL3L1 copy number variation (CNV) influences the risk of HIV-1 infection, there are still no clear conclusions. Therefore, we performed a meta-analysis using two models to generate a more robust estimate of the association between CCL3L1 CNV and susceptibility to HIV-1 infection. Methods: We divided the cases and controls into two parts as individuals with CCL3L1 gene copy number (GCN) above the population specific median copy number (PMN) and individuals with CCL3L1 GCN below PMN, respectively. Odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were given for the main analysis. We also conducted stratified analyses by ethnicity, age group and sample size. Relevant literatures were searched through PubMed and ISI Web of Knowledge up t

Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30–64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35–p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis. © 1999 Cancer Research Campaig

Characterization of indeterminate spleen lesions in primary CT after blunt abdominal trauma: potential role of MR imaging

The purpose of this study was to determine the value of magnetic resonance imaging (MRI) for characterization of indeterminate spleen lesions in primary computed tomography (CT) of patients with blunt abdominal trauma. Twenty-five consecutive patients (8 female, 17 male, mean age 51.6 ± 22.4 years) with an indeterminate spleen lesion diagnosed at CT after blunt abdominal trauma underwent MRI with T2- and T1-weighted images pre- and post-contrast material administration. MRI studies were reviewed by two radiologists. Age, gender, injury mechanism, injury severity score (ISS), management of patients, time interval between CT and MRI, and length of hospital stay were included into the analysis. Patient history, clinical history, imaging, and 2-month clinical outcome including review of medical records and telephone interviews served as reference standard. From the 25 indeterminate spleen lesions in CT, 11 (44 %) were traumatic; nine (36 %) were non-traumatic (pseudocysts, n = 5; hemangioma, n = 4) and five proven to represent artifacts in CT. The ISS (P  0.05). The MRI features ill-defined lesion borders, variable signal intensity on T1- and T2-weighted images depending on the age of the hematoma, focal contrast enhancement indicating traumatic pseudoaneurysm, perilesional contrast enhancement, and edema were most indicative for traumatic spleen lesions. As compared with CT (2/25), MRI (5/25) better depicted thin subcapsular hematomas as indicator of traumatic spleen injury. In conclusion, MRI shows value for characterizing indeterminate spleen lesions in primary CT after blunt abdominal trauma