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Real‐time polymerase chain reaction (PCR) for SARS‐CoV‐2 is the mainstay of COVID‐19 diagnosis, yet there are conflicting reports on its diagnostic performance. Wide ranges of false‐negative PCR tests have been reported depending on clinical presentation, the timing of testing, specimens tested, testing method, and reference standard used. We aimed to estimate the frequency of discordance between initial nasopharyngeal (NP) PCR and repeat NP sampling PCR and serology in acutely ill patients admitted to the hospital. Panel diagnosis of COVID‐19 infection is further utilized in discordance analysis. Included in the study were 160 patients initially tested by NP PCR with repeat NP sampling PCR and/or serology performed. The percent agreement between initial and repeat PCR was 96.7%, while the percent agreement between initial PCR and serology was 98.9%. There were 5 (3.1%) cases with discordance on repeat testing. After discordance analysis, 2 (1.4%) true cases tested negative on initial PCR. Using available diagnostic methods, discordance on repeat NP sampling PCR and/or serology is a rare occurrence.

BackgroundCOVID-19 caused by the novel coronavirus SARS-CoV-2 has caused the greatest public health emergency of our time. Accurate laboratory detection of the virus is critical in order to contain the spread. Although real-time polymerase chain reaction (PCR) has been the cornerstone of laboratory diagnosis, there have been conflicting reports on the diagnostic accuracy of this method.MethodsA retrospective review was performed on all hospitalized patients tested for SARS-CoV-2 (at St. Pauls Hospital in Vancouver, BC) from March 13 – April 12, 2020. Diagnostic accuracy of initial PCR on nasopharyngeal (NP) swabs was determined against a composite reference standard which included a clinical assessment of the likelihood of COVID-19 by medical experts, initial and repeat PCR, and post-hoc serological testing.ResultsA total of 323 patients were included in the study, 33 (10.2%) tested positive and 290 (89.8%) tested negative by initial PCR. Patients testing positive were more likely to exhibit features of cough (66.7% vs 39.3%), shortness of breath (63.6% vs 35.9%), fever (72.7% vs 27.6%), radiographic findings (83.3% vs 39.6%) and severe outcomes including ICU admission (24.2% vs 9.7%) and mortality (21.2% vs 6.2%) compared to patients testing negative. Serology was performed on 90 patients and correlation between serology and PCR was 98.9%. There were 90 patients included in the composite reference standard. Compared to the composite reference standard, initial PCR had sensitivity of 94.7% (95% CI 74.0 to 99.9%), specificity of 100% (95% CI 94.9 to 100%), positive predictive value of 100% (95% CI 81.5 to 100%) and a negative predictive value of 98.6% (95% CI 92.5 to 100%).DiscussionOur study showed high sensitivity of PCR on NP swab specimens when compared to composite reference standard in hospitalized patients. High correlation of PCR with serological testing further increased confidence in the diagnostic reliability of properly collected NP swabs.

Highlights • SARS-CoV-2 serology offers limited clinical utility for individuals. • SARS-CoV-2 serology may be useful for seroprevalence studies. • Claims regarding protective immunity or infectivity cannot be made using serology. • Assay clinical sensitivity and specificity should approach 100%. • Harmonized reporting of SARS-CoV-2 serology minimizes result misinterpretation., Clinical laboratories across the world are working to validate and perform testing for SARS-CoV-2 antibodies. Herein, we present interim consensus guidance for Canadian clinical laboratories testing and reporting SARS-CoV-2 serology, with emphasis on the capabilities and limitations of these tests and recommendations for interpretative comments in an effort to achieve harmonized laboratory practices. The consensus document provides a broad overview of topics including sample type and contamination risk; kinetics of antibody response to COVID-19 and the impact on serology testing; clinical utility of SARS-CoV-2 serology testing; clinical performance of commercial laboratory-based assays commonly deployed in North America; recommendations for interim reporting; utility of SARS-CoV-2 antibody testing for pediatric patients; and utility of point-of-care testing. The information is based on the current literature and is subject to change as additional information becomes available.

Objectives Regular measurement of glycated hemoglobin (A1C) is logistically demanding. Home blotter-paper collection offers an alternative. This study tested the viability of at-home blotter-paper A1C measurement. Methods Objective: compare accuracy of A1C levels collected on blotter paper at home (home-blotter) and blotter-paper collection in laboratory (lab-blotter) with venous A1C (routine measurement). Agreement was assessed by Pearson correlation, Lin concordance correlation coefficient (CCC), positive and negative predictive values (PPVs, NPVs) and Bland-Altman plots and associated statistics. Results Home-blotter, lab-blotter and venous A1C correlated strongly (0.93, 0.93). Home- and lab-blotter results were upwardly biased (0.387%, 0.1%). Bias increased with time. Bias correction provided agreement for both blotters (CCC >0.9); blotters correctly identifying levels above 7% (53 mmol/mol) were 100% for corrected home-blotters and 87% (95% confidence interval) for corrected lab-blotters. NPVs (% blotters correctly identifying levels of 7% or lower [53 mmol/mol]) were 100% for corrected home-blotters and 83% for corrected lab-blotters. After correction, >92% of corrected blotters had errors of 8% or less. Of our subjects, 88.5% found home sampling preferable to routine laboratory sampling. Conclusions Home-blotter collection is an alternative to routine collection.

Treatment of ( Z )-3-deoxy-1,2:5,6-di- O -isopropylidine-3- C -(methoxycarbonyl)-methylene-α- d - ribo -hexofuranose (1) with diazomethane in ether afforded the unstable Δ 1 - and Δ 2 -pyrazolines 2 and 2a . High-pressure hydrogenation of the latter compounds over Raney nickel afforded a mixture of amines 3, 5, 7 , and 9 (in 80% yield), which were separated by chromatography. Acetylation of these compounds yielded the N -acetyl derivatives 4, 6, 8 , and 10 . X-Ray analysis of compounds 8 and 10 showed them to be spiro-3,4′-( R )-(3-deoxy-1,2:5,6-di- O -isopropylidine-α- d - ribo -hexofuranose)-3′-( R )-[and 3′-( S )]-acetamido-2′-pyrrolidinone, respectively. The structures of compounds 4 and 6 (determined by chemical means) were the corresponding spiro-3,4′-( S )-3′-( R )-acetamido-2′-pyrrolidinone and 3′-( S )-acetamido-2′-pyrrolidinone, respectively.

A one year old North American Indian boy who presented with episodes of vomiting, lethargy and periodic hypoglycaemia was shown to have hereditary fructose intolerance. A liver biopsy showed typical histological changes and fructose-l-phosphate aldolase activity was greatly diminished. Although blood fructose increased only slightly during an oral fructose tolerance test, he developed severe hypoglycaemia which did not respond to glucagon. Insulin levels remained low. Plasma lactic acid, uric acid, magnesium, methionine, valine, leucine, isoleucine and aspartate aminotransferase rose during the test while potassium and phosphate fell markedly. Continuous EEG monitoring showed no significant changes, but an ECG showed a slight cardiac arrhythmia when potassium was at its lowest level. Urinary excretion of uric acid and magnesium increased during the fructose load, but there was no rise in the excretion of potassium, phosphate, or bicarbonate. Patients with hereditary fructose intolerance may exhibit a Fanconi syndrome and this has been blamed for the falling plasma potassium during a fructose load. The hypokalemic response to acute fructose loading in this patient has been demonstrated not to be due to renal losses. We speculate that potassium probably entered the intracellular space when fructose was administered.