Trace elements, such as iodine and selenium, are closely related to autoimmune thyroiditis and thyroid function. Low serum magnesium is associated with several chronic diseases; however, its associations with autoimmune thyroiditis and thyroid function are unclear. We investigated the relationships between low serum magnesium, autoimmune thyroiditis, and thyroid function in 1,257 Chinese participants. Demographic data were collected via questionnaires, and levels of serum thyroid stimulating hormone, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody (TGAb), free thyroxine, serum magnesium, serum iodine, and urinary iodine concentration were measured. Participants were divided into serum magnesium level quartiles (≤0.55, 0.551–0.85, 0.851–1.15, and >1.15 mmol/L). The median serum magnesium level was 0.89 (0.73–1.06) mmol/L; levels ≤0.55 mmol/L were considered severely low (5.9% of participants). The risks of TGAb positivity and Hashimoto thyroiditis (HT) diagnosed using ultrasonography in the lowest quartile group were higher than those in the adequate magnesium group (0.851–1.15 mmol/L) (p < 0.01, odds ratios [ORs] = 2.748–3.236). The risks of total and subclinical-only hypothyroidism in the lowest quartile group were higher than those in the adequate magnesium group (0.851–1.15 mmol/L) (p < 0.01, ORs = 4.482–4.971). Severely low serum magnesium levels are associated with an increased rate of TGAb positivity, HT, and hypothyroidism.
In vivo demonstration of hypoxia is of significance for tumour patient management. Fluorine-18 fluoromisonidazole ([18F]FMISO) is a proven hypoxic imaging agent. We developed an [18F]FMISO tumour to muscle retention ratio (TMRR) for the detection of tumour hypoxia in nasopharyngeal carcinoma (NPC). Data were acquired by positron emission tomography (PET) of the nasopharynx and neck after intravenous injection of 370 MBq of [18F]FMISO. Two imaging protocols were adopted: a long protocol for comprehensive dynamic information and a short protocol for a simple, clinically convenient imaging procedure. Tomograms were reconstructed and evaluated visually. ROI analysis on the basis of time-activity curve evaluation was performed to calculate the TMRR of NPC or cervical nodal metastases (CNMs) in relation to the suboccipital muscles at 2 h. The calculation of the TMRR was exactly the same for both the long and the short protocol as two 30-min composite frames had been created immediately after intravenous injection and 2 h after injection of [18F]FMISO in the long protocol. The normal tissue to muscle retention ratio (NTMRR) was derived similarly from the normal nasopharynx. The data of 12 controls and 24 patients with NPC were analysed. The long protocol was used in 15 patients, and the short protocol in nine. In controls, the mean NTMRR+/-1 SD was 0.96+/-0.14. The mean TMRRs for NPC and CNMs were 2.56+/-1.50 and 1.35+/-0.51, respectively; these values were significantly higher than the mean NTMRR for normal controls (P<0.005 in each case). At the retention threshold value of 1.24, tumour hypoxia occurred in 100% of the primary lesions of NPC and 58% of CNMs. The TMRR for undifferentiated carcinoma was significantly lower than that for non-keratinized carcinoma (P<0.05). The [18F]FMISO TMRR is a simple and clinically useful index for detecting tumour hypoxia in NPC.
SARS-CoV-2 pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared to the nasopharyngeal swab. We compared rRT-PCR Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a non-hospitalized, ambulatory cohort of COVID-19 patients at multiple time points. There were 171 matched specimen pairs. Compared to nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid collection device increased the percent positive agreement from 37.2% (16/43) to 44.6% (29/65). The percent positive agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample. In this study of non-hospitalized SARS-CoV-2 infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared to nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection, and the time from symptom onset especially in outpatient populations.
COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases.
In an outpatient cohort in Maryland, clustering of SARS-CoV-2 positivity within households was high, with 76% of 74 households reporting at least one other symptomatic person and 66% reporting another person who tested SARS-CoV-2 positive. SARS-CoV-2 positivity among household members was associated with larger household size and bedroom sharing.
The incidence of long COVID is substantial, even in people who did not require hospitalization for acute COVID–19. The pathobiological mechanisms of long COVID and the role of early viral kinetics in its development are largely unknown. Seventy–three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS–CoV–2 RT–PCR test, and mid–turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS–CoV–2 using RT–PCR and additional test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1, 3, 6, 12, and 18 months post–COVID–19 diagnosis. Time from acute COVID–19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90 or more days from acute COVID–19 symptom onset. Brain fog and muscle pain at 90 or more days after acute COVID–19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID–19 onset with adjustment for age, sex, BMI over 25, and COVID vaccination status prior to COVID–19 (brain fog: aRR 0.46, 95% CI 0.22 – 0.95; muscle pain: aRR 0.28, 95% CI 0.08 – 0.94). This work indicates that at least two long COVID symptoms, brain fog and muscle pain, at 90 or more days from acute COVID–19 onset are specifically associated with longer time to clearance of SARS–CoV–2 RNA from the upper respiratory tract.
In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.
Background Viral and immune kinetics in mild to moderate COVID-19 are understudied because of challenges inherent in longitudinal sampling of people who are infectious to others, feeling ill, yet are not hospitalized. In particular, sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common and confounds surveillance efforts in the community. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection via longitudinal viral RNA, virus culture, and plasma and oral fluid antibody sampling in a prospective observational cohort study of adult outpatients with COVID-19. Methods and Findings Samples from 95 non-hospitalized participants ≥ 30 years old with recent COVID-19 diagnosis and known symptom onset date were analyzed. Participants self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. SARS-CoV-2 RT-PCR performed on 507 URT samples revealed a median time to viral RNA clearance of the URT of 33.5 days. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 spike-receptor binding domain (S-RBD) antibodies. The kinetics of oral fluid anti-SARS-Cov-2 antibodies were measured using a multiplex immunoassay. The mean time to first detection of oral fluid anti-SARS-CoV-2 antibodies was 8-13 days post-symptom onset. Associations of symptoms, host demographics, comorbidities, and immune kinetics with time to SARS-CoV-2 RNA clearance were estimated using Cox proportional hazards models. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies was independently associated with a longer time to SARS-CoV-2 viral RNA clearance (aHR 0.96, 95% CI 0.92-0.99, p=0.020). BMI ≥ 25kg/m2 was also independently associated with a longer time to viral RNA clearance (aHR 0.37, 95% CI 0.18-0.78, p=0.009). Fever reported as one of first three COVID-19 symptoms was associated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). Plasma titers of neutralizing antibodies, SARS-CoV-2 spike (S) antibodies, and S-receptor binding domain (S-RBD) antibodies were obtained at 1-4 months post-symptom onset. BMI was positively correlated with post-acute plasma SARS-CoV-2-specific neutralizing antibody titer and anti-S-RBD antibody titer. Conclusions In an intensively sampled cohort of 95 adult outpatients with COVID-19, we demonstrate that longer time to first detection of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with longer time to viral RNA clearance. This work provides insights into the host and immune factors most important for viral clearance in mild to moderate COVID-19.
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