Smudge cells.

Smudge cells can be defined as ruptured or destroyed cells - most commonly lymphocytes where cytoplasm and nuclei get smudged during smear test of the patient's blood/preparation of slides. When finding smudge cells, it is recommended to control the lab work frequently. If a persistent or higher number of smudge cells are found during 3 months, it should lead to a referral to the hematologist. The purpose of this review is to give an overview of smudge cells and conditions in which they can be found, as well as management of the findings.

Effects of physical activity on blood lipids and HbA1c in healthy pregnant women: the FitMum randomized controlled trial.

OBJECTIVE: Maternal blood lipid and glucose concentrations during pregnancy affect fetal growth and the risk of pregnancy and delivery complications. We aimed to investigate the effects of physical activity (PA) during pregnancy on maternal blood lipid and hemoglobin A1c (HbA1c) concentrations. We hypothesized that higher PA was associated with improved lipid profile and glycemic control. METHODS: In a secondary analysis of a randomized controlled trial, we included 216 pregnant women before week 15+0 and tested the effects of two different PA interventions throughout pregnancy compared to standard care on maternal blood lipid and HbA1c concentrations. Additionally, we investigated the effect of PA per se measured by an activity tracker. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, and HbA1c concentrations were measured at week ≤15+0, 28+0-6, 34+0-6, and at delivery (week 32+1 to 42+0). Effects of the interventions and PA per se were tested using linear mixed effects models and linear regression analyses, respectively. RESULTS: No effects of the PA interventions were detected on maternal lipids or HbA1c during pregnancy. In PA per se analyses, more minutes per week of moderate-to-vigorous intensity PA were associated with less increase in TC (-1.3E-04, p=0.020) and LDL-C (-8.5E-05, p=0.035) as pregnancy progresses. More active kilocalories were associated with less increase in TC (-5.5E-05, p<0.001), HDL-C (-9.5E-06, p=0.024), and LDL-C (-3.2E-05, p=0.005). CONCLUSION: Whilst there were no effects of offering PA interventions, higher PA was associated with reduced increases in total cholesterol, HDL-C, and LDL-C as pregnancy progressed.

Tenascin-C in patients with central nervous system infections.

BACKGROUND: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). METHODS: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. RESULTS: 174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. CONCLUSION: Levels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.

Collagenase-producing bacteria are common in anastomotic leakage after colorectal surgery: a systematic review.

PURPOSE: Some gut bacteria can produce enzymes (collagenases) that can break down collagen in the intestinal wall. This could be a part of the pathophysiology of anastomotic leakage (AL). This systematic review aimed to investigate if such bacteria were present more frequently in AL patients versus non-AL patients following colorectal surgery. METHODS: This systematic review was reported according to the PRISMA and AMSTAR guidelines. Before the literature search, a study protocol was registered at PROSPERO (CRD42022363454). We searched PubMed, EMBASE, Google Scholar, and Cochrane CENTRAL on April 9th, 2023, for randomized and observational human studies of AL following colorectal surgery with information on gastrointestinal bacteria. The primary outcome was bacteria with the potential to produce collagenase. The risk of bias was assessed with the Newcastle-Ottawa Scale, as all studies were observational. RESULTS: We included 15 studies, with a total of 52,945 patients, of which 1,747 had AL, and bacteriological information from feces, mucosa, the resected specimen, or drain fluid was presented. In 10 of the 15 studies, one or more collagenase-producing bacteria were identified in the patients with AL. Neither the bacteria nor the collagenase production were quantified in any of the studies. The studies varied greatly in terms of sample material, analytical method, and time of collection. Studies using DNA sequencing methods did not report findings of collagenase-producing bacteria. CONCLUSION: Collagenase-producing bacteria are more common in patients with AL following colorectal surgery than in patients without AL, but the significance is unclear. From the current studies, it is not possible to determine the pathogenicity of the individual gut bacteria.

Paediatric reference ranges for plasma chromogranin A.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare diseases with varied aggressiveness originating from endocrine cells belonging to the diffuse endocrine system and most often produce and secrete chromogranin A (CgA). CgA in plasma is therefore used to screen, diagnose, and monitor for NENs in both adults and children with sporadic or familial NENs. METHODS: Plasma CgA was measured using the Brahms Kryptor assay in 268 healthy children/adolescents; 85 children were tested as part of a familial cancer screening program and 183 additional children younger than 20 years of age underwent screening for allergies. Repeated measurements (month - years) was used to calculate the intra-individual variation. The dataset was analysed in R using the referenceInterval package. RESULTS: The plasma CgA concentration decreased with age and was 32-118 µg/L for children aged 0-3 years, 18-85 µg/L for children aged 4-13 years, and 6-79 µg/L for adolescents aged 14-19 years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102 µg/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39 µg/L, respectively. The median intra-individual variation was 14% (25%-centile 9.4%/75%-centile 21%). CONCLUSIONS: The reference interval will be useful when screening, diagnosing, and monitoring children for NENs respecting the limitations plasma CgA has.

A Novel Approach to Predicting Early Pregnancy Outcomes Dynamically in a Prospective Cohort Using Repeated Ultrasound and Serum Biomarkers.

This study aimed to develop a dynamic model for predicting outcome during the first trimester of pregnancy using baseline demographic data and serially collected blood samples and transvaginal sonographies. A prospective cohort of 203 unselected women with an assumed healthy pregnancy of < 8 weeks' gestation was followed fortnightly from 4-14 weeks' gestation until either miscarriage or confirmed first trimester viability. The main outcome was development of a model to predict outcome from gestational age-dependent hazard ratios using both baseline and updated serial data from each visit. Secondary outcomes were descriptions of risk factors for miscarriage. The results showed that 18% of the women experienced miscarriages. A fetal heart rate detected before 8 weeks' gestation indicated a 90% (95% CI 85-95%) chance of subsequent delivery. Maternal age (≥ 35 years), insufficient crown-rump-length (CRL) and mean gestational sac diameter (MSD) development, and presence of bleeding increased the risk of miscarriage. Serum biomarkers, including hCG, progesterone, and estradiol, were found to impact the risk of miscarriage with estradiol as the most important. The best model to predict miscarriage was a combination of maternal age, vaginal bleeding, CRL, and hCG. The second-best model was the sonography-absent model of maternal age, bleeding, hCG, and estradiol. This study suggests that combining maternal age, and evolving data from hCG, estradiol, CRL, and bleeding could be used to predict fetal outcome during the first trimester of pregnancy.Trial registration ClinicalTrials.gov identifier: NCT02761772.

Evaluation of four laboratory-based high-throughput SARS-CoV-2 automated antigen tests compared to RT-PCR on nasal and oropharyngeal samples.

BACKGROUND: The demand for RT-PCR testing has been unprecedented during the SARS-CoV-2 pandemic. Fully automated antigen tests (AAT) are less cumbersome than RT-PCR, but data on performance compared to RT-PCR are scarce. METHODS: The study consists of two parts. A retrospective analytical part, comparing the performance of four different AAT on 100 negative and 204 RT-PCR positive deep oropharyngeal samples divided into four groups based on RT-PCR cycle of quantification levels. In the prospective clinical part, 206 individuals positive for and 199 individuals negative for SARS-CoV-2 were sampled from either the anterior nasal cavity (mid-turbinate) or by deep oropharyngeal swabs or both. The performance of AATs was compared to RT-PCR. RESULTS: The overall analytical sensitivity of the AATs differed significantly from 42% (95% CI 35-49) to 60% (95% CI 53-67) with 100% analytical specificity. Clinical sensitivity of the AATs differed significantly from 26% (95% CI 20-32) to 88% (95% CI 84-93) with significant higher sensitivity for mid-turbinate nasal swabs compared to deep oropharyngeal swabs. Clinical specificity varied from 97% to 100%. CONCLUSION: All AATs were highly specific for detection of SARS-CoV-2. Three of the four AATs were significantly more sensitive than the fourth AAT both in terms of analytical and clinical sensitivity. Anatomical test location significantly influenced the clinical sensitivity of AATs.

Hearing Loss in Bacterial Meningitis Revisited-Evolution and Recovery.

Background: Hearing loss and deafness are well-known sequelae from bacterial meningitis (ABM) and may result in social dysfunction and learning difficulties. Yet, the timely development of hearing loss and restitution is poorly studied, especially among adults. Hearing loss was revisited using otoacoustic emissions (OAEs) to determine the occurrence, magnitude, and development of hearing loss among adults with ABM. Methods: Distortion product OAEs were measured in patients with ABM the day of admission and days 2, 3, 5-7, and 10-14 and at follow-up 30-60 days after discharge. Frequencies were categorized as low (1, 1.5, 2 kHz), mid (3, 4, 5 kHz), mid-high (6, 7, 8 kHz), and high (9, 10 kHz). Audiometry was performed on discharge and 60 days after. Results were compared with 158 healthy controls. Results: OAE was obtained in 32 patients. ABM was due to S. pneumoniae in 12 patients (38%). All patients were treated with dexamethasone. OAE emission threshold levels (ETLs) were significantly decreased upon admission and at follow-up in all frequencies compared with healthy controls. A substantial and significant decrease in ETLs was found in S. pneumoniae meningitis. Sensorineural hearing loss (SNHL) >20 dB was present in 13 of 23 (57%) at discharge and in 11 of 18 patients (61%) 60 days after discharge. Hearing recovery decreased from day 3. Conclusions: Hearing loss in ABM still affects >60% of patients despite treatment with dexamethasone. In S. pneumoniae meningitis, SNHL is profound and permanent. A window of opportunity for systemic or local treatments aiming to preserve cochlear function is proposed.

Pentraxin 3 in the cerebrospinal fluid during central nervous system infections: A retrospective cohort study.

The present study describes diagnostic and prognostic abilities of Cerebrospinal fluid (CSF) Pentraxin 3 (PTX3) in central nervous system (CNS) infections. CSF PTX3 was measured retrospectively from 174 patients admitted under suspicion of CNS infection. Medians, ROC curves and Youdens index was calculated. CSF PTX3 was significantly higher among all CNS infections and undetectable in most of the patients in the control group, and significantly higher in bacterial infections compared to viral and Lyme infections. No association was found between CSF PTX3 and Glasgow Outcome Score. PTX3 in the CSF can distinguish bacterial infection from viral and Lyme infections and non-CNS infections. Highest levels were found in bacterial meningitis. No prognostic abilities were found.

A novel hepcidin mutation.

BACKGROUND: The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue. METHODS: Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). RESULTS: A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma. The patient had massive iron overload with ferritin up to 8360 µg/L. He was anaemic with a Hb at 7.0 mmol/L (11.3 g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2 nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality. CONCLUSION: A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.

Sensitivity and performance of three novel quantitative assays of SARS-CoV-2 nucleoprotein in blood.

To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. A total of 272 plasma samples collected in the period November-December 2021 were analyzed by the methods Simoa SARS CoV-2 N Protein Advantage Kit [Quanterix Simoa], Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) [Solsten ELISA], and Elecsys SARS-CoV-2 Antigen electrochemiluminescence immunoassay [Elecsys ECLIA]. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays. The SARS CoV-2 PCR-status was not known for the patients. Linear correlation in the pairwise correlation between assays as well as linearity of dilution series of inactivated virus culture was estimated by Spearman score. Sensitivity and specificity were estimated by pairwise comparison. The three assays showed poor agreement on patient samples with regards to concentration. Performance on virus culture was excellent but with different level of detection (LOD). Positive vs negative results show comparable sensitivity and specificity of Quanterix Simoa and Solsten ELISA, with a higher LOD in Elecsys ECLIA and thus lower sensitivity and high specificity. N by all tested assays can be used as a marker for systemic COVID-19 disease.

Validation and advantages of using novel RT-qPCR melting curve analysis assays for the identification of SARS-CoV-2 variants.

Reverse transcription quantitative PCR (RT-qPCR) assays are gold standard in diagnosing SARS-CoV-2 infection and play a major role in viral subtyping for rapid detection and monitoring of important mutations, containing the spread of new virus variants. We wanted to compare RT-qPCR melting curve analysis assays to Sanger Sequencing for detection of variants within the SARS-CoV-2 spike glycoprotein and examined their sensitivity and specificity. Samples positive for SARS-CoV-2 (n = 663 + 82) were subtyped using both Sanger sequencing and five RT-qPCR melting curve analysis assays specific for the mutations N501Y, P681H, E484K, K417N/T, and N439K. The results of the two methods were compared. The training cohort and the clinical validation cohort showed equally, or significantly better sensitivity of the assays compared to the Sanger sequencing. The agreement of the Sanger sequencing and the assays ranged from 92.6 to 100% for the training cohort and 99.4-100% for the clinical validation. The sensitivity, specificity, and turn-around time of the RT-qPCR melting curve analysis assays are well-suited for clinical monitoring of VOCs, making the assays an important tool in contact tracing and risk stratification. Furthermore, the assays were able to indicate the presence of new mutations in the complementary sequence to the mutation-specific probes.

von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

Varying fecal immunochemical test screening cutoffs by age and gender: a way to increase detection rates and reduce the number of colonoscopies.

BACKGROUND AND AIMS: Most colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) use the same cutoff value for all participants. This study aimed at finding age- and gender-specific cutoff values that can improve population-based CRC screening. METHODS: This observational study used data from the first 2 years of the Danish FIT-based CRC screening program to estimate sensitivity, specificity, number of positive tests, number of screen-detected cancers and adenomas, and number of interval cancers for various cutoff values for different male and female age groups. RESULTS: Data from 531,828 participants showed that lower cutoff values for older residents and higher cutoff values for younger residents increased the overall sensitivity and specificity, decreased the number of needed colonoscopies by 7%, increased the number of screen-detected cancer by 1.1%, increased the number of screen-detected adenomas by 5%, and decreased the number of interval cancers by approximately 1.5%. However, these cutoff values also increased an inequality in sensitivity and specificity. Choosing cutoff values that ensured equal sensitivity between the groups, however, did increase inequality in, for example, the interval cancer rate. CONCLUSIONS: In a FIT-based CRC program it is possible to decrease the number of needed colonoscopies while at the same time to increase overall sensitivity and specificity and detect more cancers and adenomas by using different cutoff values for different male and female age groups. However, this increases inequality in sensitivity and specificity, whereas other strategies like ensuring equal sensitivity could be considered.

A non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA.

The current nucleic acid signal amplification methods for SARS-CoV-2 RNA detection heavily rely on the functions of biological enzymes which imposes stringent transportation and storage conditions, high cost and global supply shortages. Here, a non-enzymatic whole genome detection method based on a simple isothermal signal amplification approach is developed for rapid detection of SARS-CoV-2 RNA and potentially any types of nucleic acids regardless of their size. The assay, termed non-enzymatic isothermal strand displacement and amplification (NISDA), is able to quantify 10 RNA copies.µL-1. In 164 clinical oropharyngeal RNA samples, NISDA assay is 100 % specific, and it is 96.77% and 100% sensitive when setting up in the laboratory and hospital, respectively. The NISDA assay does not require RNA reverse-transcription step and is fast (<30 min), affordable, highly robust at room temperature (>1 month), isothermal (42 °C) and user-friendly, making it an excellent assay for broad-based testing.

The optimal cut-off value in fit-based colorectal cancer screening: An observational study.

BACKGROUND: Colorectal cancer (CRC) screening programs using fecal immunochemical test (FIT) have to choose a cut-off value to decide which citizens to recall for colonoscopy. The evidence on the optimal cut-off value is sparse and based on studies with a low number of cancer cases. METHODS: This observational study used data from the Danish Colorectal Cancer Screening Database. Sensitivity and specificity were estimated for various cut-off values based on a large number of cancers. Traditionally optimal cut-off values are found by weighting sensitivity and specificity equally. As this might result in too many unnecessary colonoscopies we also provide optimal cut-off values for different weighting of sensitivity and specificity/number of needed colonoscopies to detect one cancer. RESULTS: Weighting sensitivity and specificity equally gives an optimal cut-off value of 45 ng Hb/ml. This, however, means making 24 colonoscopies to detect one cancer. Weighting sensitivity lower and for example, aiming at making about 16 colonoscopies to detect one cancer, gives an optimal cut-off value of 125 ng Hb/ml. CONCLUSIONS: The optimal cut-off value in an FIT population-based screening program is 45 ng Hb/ml, when as traditionally sensitivity and specificity are weighted equally. If, however, 24 colonoscopies needed to detect one cancer is too huge a burden on the health care system and the participants, 80, 125, 175, and 350 ng Hb/ml are optimal cut-off values when only 19/16/14/10 colonoscopies are accepted to find one cancer.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.