Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association of Modified Systemic Lupus Erythematosus Responder Index Attainment With Long-Term Clinical Outcomes: A Five-Year Prospective Study.

OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up. METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied. RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P < 0.05 for damage accrual ORs at all time points). CONCLUSION: In SLE patients with active disease receiving standard of care, mSRI attainment predicts favorable outcomes over long-term follow-up, supporting the clinical meaningfulness of SRI attainment as an SLE trial end point.

Performance of the Roche/Snibe electrochemiluminescent anti-SARS-COV-2 spike assays compared to the Roche/Abbott IgG nucleocapsid and Abbott IgM spike assays.

INTRODUCTION: We evaluated the Roche Elecsys Anti-SARS-CoV-2 and Snibe SARS-CoV-2 S-RBD IgG spike chemiluminescent immunoassays and compared them to existing Roche/Abbott nucleocapsid and Abbott IgM spike assays. METHODS: We enrolled 184 SARS-CoV-2 RT-PCR positive samples and 215 controls (172 pre-pandemic, and 43 cross-reactivity) to evaluate the Roche spike antibody (anti-SARS-CoV-2-S) assay. For the Snibe evaluation, we included 119 RT-PCR positive samples and 249 controls (200 pre-pandemice, 49 cross-reactivity). 98 cases had been tested on three spike assays (Roche total antibody, Snibe IgG and Abbott IgM). RESULTS: The Roche anti-SARS-CoV-2-S assay had a CV of 0.5% (0.82U/mL) and 2.3% (8.72U/mL) and was linear from 1.16 to 240U/mL. The Snibe assay was linear from 6.43 to 77.7AU/mL, CV of 5.5% (0.43AU/mL) and 8.8% (0.18AU/mL). The Snibe spike assay was significantly more sensitive than the Abbott IgG assay at 0-6 days POS (35.2% vs 3.6%, mean difference 29.6%, 95% CI 17.5 to 41.8, p < 0.0001). Optimized LORs significantly improved the sensitivity of the Roche spike (48.1%-56.7%) and both nucleocapsid assays (Roche 43.3%-65.5%, Abbott 3.6%-18.5%) in early disease. CONCLUSION: Although both spike assays showed higher sensitivity than their nucleocapsid counterparts, lower, optimized LORs provided the most significant improvements to sensitivity.

Burnout and well-being in young doctors in Hong Kong: a territory-wide cross-sectional survey.

INTRODUCTION: This territory-wide study evaluated the level of burnout and health status among young doctors in Hong Kong. METHODS: All young doctors in Hong Kong, defined as residents-in-training or doctors within 10 years of their specialist registration, were invited to participate in an online cross-sectional survey. This survey used standardised questionnaires including the Copenhagen Burnout Inventory (CBI) for burnout, Patient Health Questionnaire-9 for depression, and general health questionnaires. RESULTS: In total, 514 doctors completed the survey; 284 were doctors within 10 years of their specialist registration, while 230 were residents-in-training. There were 277 women (54%); among all respondents, the mean age was 33.7 ± 6.1 years. Using a CBI subscale cut-off score of ≥50 (moderate and higher), 72.6% (n=373) of respondents reported personal burnout; 70.6% (n=363) of respondents reported work-related burnout; and 55.4% (n=285) of respondents reported client-related burnout. Furthermore, 24% (n=125) of respondents were "somewhat dissatisfied" with their present job position; 4% (n=19) of respondents were "very dissatisfied" with their present job position. The prevalence of depression among respondents was 21% (n=110). CONCLUSIONS: In this territory-wide cross-sectional survey of young doctors in Hong Kong, a high prevalence of burnout was identified among young doctors; respondents exhibited a considerable level of depression and substantial dissatisfaction with their current positions. Strategies to address these problems must be formulated to ensure the future well-being of the medical and dental workforce in Hong Kong.

Evaluation of automated antigen detection test for detection of SARS-CoV-2.

RT-PCR is the gold standard to detect SARS-CoV-2, however, its capacity is limited. We evaluated an automated antigen detection (AAD) test, Elecsys SARS-CoV-2 Antigen (Roche, Germany), for detecting SARS-CoV-2. We compared the limit of detection (LOD) between AAD test, rapid antigen detection (RAD) test; SARS-CoV-2 Rapid Antigen Test (SD Biosensor, Korea), and in-house RT-PCR test. LOD results showed that the AAD test was 100 fold more sensitive than the RAD test, while the sensitivity of the AAD test was comparable to the RT-PCR test. The AAD test detected between 85.7% and 88.6% of RT-PCR-positive specimens collected from COVID-19 patients, false negative results were observed for specimens with Ct values >30. Although clinical sensitivity for the AAD test was not superior or comparable to the RT-PCR test in the present study, the AAD test may be an alternative to RT-PCR test in terms of turn-around time and throughput.

Performance of the Roche IL-6 chemiluminescent immunoassay in patients with COVID-like respiratory symptoms.

INTRODUCTION: We evaluated the Roche Elecsys IL6 assay on the Cobas immunoassay analyser. METHOD: Serum IL6 of 144 controls were compared to 52 samples from patients with COVID-like respiratory symptoms (17 SARS-CoV-2 RT-PCR positive); 25 of these were from the intensive care unit (ICU). We compared the IL6 levels to C-reactive protein (CRP) and procalcitonin (PCT) levels in all cases. RESULTS: The IL6 assay had coefficient-of-variation (CV) of 2.3 % (34.1 pg/mL) and 2.5 % (222.5 pg/mL), a limit of quantitation <1.6 pg/mL, and was linear from 1.6 to 4948 pg/mL. There was a significant difference in IL6 values between patients with COVID-like respiratory symptoms versus controls (p < 0.001). ROC analysis showed that IL6 > 6.4 pg/mL identified symptomatic cases (AUC 0.94, sensitivity 88.2 %, specificity 97.2 %). There was a significant difference between the IL6 of symptomatic ICU/non-ICU cases (median IL6 228 vs 11 pg/mL, p < 0.0001); ROC analysis showed IL6 > 75 pg/mL (sensitivity 76.0 %, specificity 88.9 %) was superior to CRP and PCT in predicting ICU admission (AUC: IL6 0.83, CRP 0.71, PCT 0.82). CONCLUSION: The performance of Elecsys IL6 assay is in keeping with the manufacturer's claims. IL6 > 6.4 pg/mL differentiates healthy from suspected COVID-19 cases and appears to be raised earlier than the other inflammatory markers in some cases. IL6 > 75 pg/mL was a good predictor of ICU admission.

Epidemiology and outcomes of geriatric and non-geriatric patients with drug allergy labels in Hong Kong.

INTRODUCTION: Adverse drug reactions are more common in geriatric patients than in younger patients, but there have been insufficient studies concerning the epidemiology or burden of drug allergy labels in geriatric patients. We prospectively investigated the prevalence and outcomes of geriatric patients with drug allergy labels in a cohort of hospitalised patients. METHODS: Patients admitted to a regional hospital over a 6-month period were recruited for this study. All patients with drug allergy labels were prospectively followed until discharge; clinical data were anonymously extracted for analyses. Patients were categorised into either geriatric (aged ≥65 years) or non-geriatric (aged <65 years) groups. Demographic characteristics, clinical outcomes, and prevalences of drug allergy labels were compared between groups. RESULTS: There were 4361 admissions involving 3641 patients during the 6-month study period. Overall, 492 patients (13.5%) had drug allergy labels, consisting of 151 non-geriatric patients (30.7%) and 341 geriatric patients (69.3%). The prevalence of drug allergy labels did not significantly differ between geriatric and non-geriatric patients (13.5% vs 13.5%, P=0.976). Significantly more patients in the geriatric group had drug allergy labels to cardiovascular system drugs (15.5% vs 4.6%, P=0.001). Geriatric patients had a significantly lower rate of direct discharge from the hospital (73.0% vs 88.1%, P<0.001) and required transfers to convalescent or rehabilitation care for further management. CONCLUSIONS: More than 13% of hospitalised geriatric patients had drug allergy labels. The leading causes of drug allergy labels were similar between geriatric and non-geriatric patients. Geriatric patients with drug allergy labels had significantly more labelled allergies to cardiovascular system drugs and adverse clinical outcomes.

Performance of two rapid point of care SARS-COV-2 antibody assays against laboratory-based automated chemiluminescent immunoassays for SARS-COV-2 IG-G, IG-M and total antibodies.

INTRODUCTION: We evaluated two SARS-CoV-2 antibody point-of-care tests (POCTs) (Abbott Panbio COVID-19 IgG/IgM and Roche SARS-CoV-2 Rapid Antibody tests) and compared the results to their respective chemiluminescent immunoassays (CLIAs) (Abbott Architect IgM, Architect IgG, Roche Cobas total antibody assays). METHOD: 200 pre-pandemic sera and 48 samples positive for various conditions (18 viral hepatitis, 18 dengue, 11 ANA and 1 dsDNA) were used as controls and to assess for cross-reactivity. Anonymised residual leftover sera positive for SARS-CoV-2 on RT-PCR were recruited as cases (n â€‹= â€‹133). The sensitivity/specificity/cross-reactivity/positive predictive value (PPV)/negative predictive value (NPV) of the POCTs were assessed. Concordance between the POCTs and chemiluminescent immunoassays (CLIAs) were analysed. RESULTS: Abbott/Roche POCT specificity was 98.7%/100% (95% CI 96.5-99.8/98.5-100) and sensitivity was 97.2%/97.2% (95% CI 85.5-99.9/85.5-99.9) in cases ≥14 days post-first positive RT-PCR (POS), PPV was 68.7%/100% (95% CI 41.3-87.2/94.7-100.0), and NPV was 97.4%/97.6% (95% CI 97.0-97.8/97.2-98.0). In cases ≥14 days POS, concordance of Abbott/Roche POCT and CLIAs was 97.2%/100% (35/36 and 36/36 results). The sensitivity of individual IgM-band results on both POCTs did not increase >95% even after 14 days POS (Abbott 2.78%, Roche 44.4%). CONCLUSION: Both POCTs have good specificity, little cross-reactivity with other antibodies, and sensitivity >95% when used in subjects ≥14 days POS. Analysis of individual POCT IgG/IgM-bands did not provide any additional information. POCTs can substitute for CLIAs in cases ≥14 days POS. In low prevalence areas, POCTs would be especially useful when combined with antigen testing in an orthogonal format to increase the PPV of COVID-19 results.

Evaluation of rapid antigen detection kit from the WHO Emergency Use List for detecting SARS-CoV-2.

BACKGROUND: Currently, there are two rapid antigen detection (RAD) kits from the WHO Emergency Use List for detecting SARS-CoV-2. OBJECTIVE: The Panbio COVID-19 Ag Rapid Test Device was selected to evaluate the performance for detecting SARS-CoV-2. STUDY DESIGN: Analytical sensitivity for the detection of SARS-CoV-2 virus was determined by limit of detection (LOD) using RT-PCR as a reference method. Clinical sensitivity was evaluated by using respiratory specimens collected from confirmed COVID-19 patients. RESULTS: The LOD results showed that the RAD kit was 100 fold less sensitive than RT-PCR. Clinical sensitivity of the RAD kit was 68.6 % for detecting specimens from COVID-19 patients. CONCLUSIONS: The RAD kit evaluated in the present study shared similar performance with another kit from the WHO Emergency Use List, the Standard Q COVID-19 Ag. Understanding the clinical characteristics of RAD kits can guide us to decide different testing strategies in different settings.

Analytical sensitivity and clinical sensitivity of the three rapid antigen detection kits for detection of SARS-CoV-2 virus.

BACKGROUND: Numerous rapid antigen detection (RAD) kits for diagnosing COVID-19 patients are available in the market recently. OBJECTIVE: To compare analytical sensitivity and clinical sensitivity for the three commercially available RAD kits. STUDY DESIGN: Analytical sensitivity for the detection of SARS-CoV-2 virus was determined by limit of detection (LOD) using RT-PCR as a reference method. Clinical sensitivity was evaluated by using respiratory specimens collected from confirmed COVID-19 patients. RESULTS: The LOD results showed that the three RAD kits varied from 102-105 fold less sensitive than RT-PCR. Clinical sensitivity of RAD kits ranged from 22.9 %-71.4 % for detecting specimens from COVID-19 patients. CONCLUSIONS: Although RAD kits were less sensitive than RT-PCR, understanding the clinical characteristics of different RAD kits can guide us to obtain suitable specimens for testing. The likelihood of positive results for RAD kits will be higher.

Performance of an automated chemiluminescence SARS-CoV-2 IG-G assay.

INTRODUCTION: We describe our evaluation of the Abbott SARS-CoV-2 IgG assay on the Architect immunoassay analyser. METHODS: We assessed assay precision, sensitivity, specificity, positive/negative predictive values (PPV/NPV), cross-reactivity (influenza/dengue/hepatitis B and C/rheumatoid factor/anti-nuclear/double-stranded DNA/syphilis) and sample throughput in samples from real-time polymerase chain reaction (RT-PCR) positive patients/healthcare workers (HCWs)/pre-pandemic samples. We compared the cut-off indexes (COIs) between all control samples (HCWs and pre-pandemic) to generate an optimised COI limit for reactivity. RESULTS: The assay specificity was 99.8% (n = 980) and sensitivity was 45.9-96.7% (n = 279). When tested ≥ 14 days post-positive RT-PCR (POS), the PPV/NPV was 96.4%/99.8%. The difference between the COIs of HCWs/pre-pandemic samples was small (0.01, p < 0.0001). There was minimal cross-reactivity with other antibodies. A lower COI limit for reactivity (≥0.55, using the 99th percentile COI of our controls and ROC analysis) improved diagnostic sensitivity, especially at 0-6 days POS (45.9-55.8%), with a small decrease in specificity (98.9%). The assay throughput was 100 samples in 70 min. CONCLUSION: The Abbott SARS-CoV-2 IgG assay shows excellent performance in patients ≥ 14 days POS. The difference between the COIs of HCWs and pre-pandemic samples was numerically small. A lower COI limit improves assay sensitivity with a slight decrease in specificity.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.