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Measles is a highly contagious febrile exanthematous disease caused by the measles virus. The measles virus spreads via airborne and droplet transmission and can cause severe complications, such as pneumonia, [...]

To the Editor.--Use of SARS-CoV-2 serology to assess risk of SARS-CoV-2 breakthrough infection (BTI) after COVID-19 vaccination is officially discouraged. (1) Yet some experts suggest that low SARS-CoV-2 anti-spike protein [...]

Lung cancer is the most common cause of cancer-related deaths worldwide. In advanced stages, the overall prognosis is poor, with a median survival rate of 12 to 15 months. The [...], * Context.--The immune microenvironment is involved in fundamental aspects of tumorigenesis, and immune scores are now being developed for clinical diagnostics. Objective.--To evaluate how well small diagnostic biopsies and tissue microarrays (TMAs) reflect immune cell infiltration compared to the whole tumor slide, in tissue from patients with non-small cell lung cancer. Design.--A TMA was constructed comprising tissue from surgical resection specimens of 58 patients with non-small cell lung cancer, with available preoperative biopsy material. Whole sections, biopsies, and TMA were stained for the pan-T lymphocyte marker CD3 to determine densities of tumor-infiltrating lymphocytes. Immune cell infiltration was assessed semiquantitatively as well as objectively with a microscopic grid count. For 19 of the cases, RNA sequencing data were available. Results.--The semiquantitative comparison of immune cell infiltration between the whole section and the biopsy displayed fair agreement (intraclass correlation coefficient [ICC], 0.29; P =.01; CI, 0.03-0.51). In contrast, the TMA showed substantial agreement compared with the whole slide (ICC, 0.64; P Conclusions.--Although overall lymphocyte infiltration is relatively well represented on TMAs, the representativity in diagnostic lung cancer biopsies is poor. This finding challenges the concept of using biopsies to establish immune scores as prognostic or predictive biomarkers for diagnostic applications. doi: 10.5858/arpa.2022-0327-OA

Antibody titration in transfusion medicine is a commonly used clinical assay to detect the strength of reactivity of red cell antibodies present in a patient's plasma. (1) There are a [...], * Context.--Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. Objective.--To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. Design.--Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. Results.--A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1 % (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. Conclusions.--Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making. (Arch Pathol Lab Med. 2023;147:1351-1359; doi: 10.5858/arpa.2022-0248-CP)

Clinical risk assessment for prostatic adenocarcinoma helps in determining prognosis and therapeutic decisions such as watchful waiting or active surveillance versus intervention. National Comprehensive Cancer Network (NCCN)-recommended traditional risk assessment [...], Context.--Low-risk (Gleason score 3 + 3 = 6) and intermediate-risk (Gleason score 3 + 4 = 7) prostate carcinoma cases diagnosed on needle biopsies are frequently referred for gene expression studies such as Oncotype DX to help validate the risk. Risk assessment helps in determining prognosis and therapeutic decision making. Objective.--To determine if addition of molecular testing is necessary, by evaluating its correlation with risk stratification provided by pathology report (Gleason score, Grade Group, proportion of positive cores) and serum prostate-specific antigen (PSA) level. Design.--Our institutional database was searched for cases that had Oncotype DX testing after prostate biopsy. The final risk category determined by molecular testing was compared to the risk stratification predicted by the pathology report and serum PSA levels. Cases were classified as concordant if they fell under the same National Comprehensive Cancer Network risk and recommended initial therapy group. Follow-up information on discordant cases was obtained and used to determine if risk stratification by molecular testing was superior to that obtained from the clinicopathologic data. Results.--A total of 4967 prostate biopsies (2015-2020) were screened. Of these, 131 prostate carcinoma cases (2.6%) had Oncotype DX testing and 111 of 131 cases (85%) had follow-up information. There was risk stratification concordance in 93 of 111 cases (84%). All 18 of 111 cases (16%) that were discordant had a follow-up course that matched the risk predicted by pathology data and serum PSA. Conclusions.--Risk stratification provided by information in the pathology report on routine biopsy assessment coupled with the serum PSA level is equivalent to that obtained by Oncotype DX testing. doi: 10.5858/arpa.2022-0225-OA

In December 2021, the Centers for Disease Control and Prevention (CDC) reduced the recommended COVID-19 isolation period for the general population from 10 days to 5 days after symptom onset [...]

Estimating the incidence of infections caused by SARS-CoV-2 that are frequently asymptomatic is challenging when using routine passive surveillance methods. Antibodies can provide a record of previous infection, whether symptomatic [...]

Multiple myeloma (MM) is a plasma-cell dyscrasia characterized by the accumulation of plasma cells in the bone marrow that produces an excess of clonal immunoglobulins (M-protein or monoclonal component). (1) [...], Context.-Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited. Objective.-To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma. Design.-The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility. Results.-Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF ([R.sup.2] > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing. Conclusions.-Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures.

SARS-CoV-2 is a highly transmissible and pathogenic virus that has caused serious harm to human health and public safety during the ongoing COVID-19 global pandemic. (1,2) Global COVID-19 cases now [...], Context.--Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors. Objective.--To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs. Design.--The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination. Results.--The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P Conclusions.--Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is histologically characterized by the presence of relatively rare lymphocyte-predominant (LP) cells (originally termed lymphocytic and histiocytic cells) that are surrounded by an abundance of [...], * Context.--Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is characterized by neoplastic lymphocyte-predominant cells frequently rimmed by [CD3.sup.+]/ [CD57.sup.+]/programmed death receptor-1 [(PD-1).sup.+] T cells. Because of the rarity of lymphocyte-predominant cells in most cases, flow cytometric studies on NLPHL often fail to show evidence of malignancy. Objective.--To evaluate the diagnostic utility of PD-1 in detecting NLPHL by flow cytometry, in conjunction with the CD4:CD8 ratio and the percentage of T cells doubly positive for CD4 and CD8. Design.--Flow cytometric data obtained from cases of NLPHL (n = 10), classic Hodgkin lymphoma (n = 20), B-cell non-Hodgkin lymphoma (n = 22), T-cell non-Hodgkin lymphoma (n = 5), benign lymphoid lesions (n = 20), angioimmunoblastic T-cell lymphomas (n = 6) and T-cell/ histiocyte-rich large B-cell lymphomas (n = 2) were analyzed and compared. Results.--Compared with the other groups, NLPHL showed significantly higher values in the following parameters: CD4:CD8 ratio, percentage of T cells doubly positive for CD4 and CD8, percentage of PD-1-positive T cells, and median fluorescence intensity of PD-1 expression in the doubly positive for CD4 and CD8 subset. Using a scoring system (0-4) based on arbitrary cutoffs for these 4 parameters, all 10 NLPHL cases scored 3 or higher, as compared with only 3 cases from the other groups, producing an overall sensitivity of 100% and a specificity of 96% (72 of 75). Two of the 3 outliers were non-Hodgkin lymphoma, and both showed definitive immunophenotypic abnormalities leading to the correct diagnosis. The remaining outlier was a case of T-cell/histiocyte-rich large B-cell lymphoma. Conclusions.--The inclusion of anti-PD-1 in flow cytometry is useful for detecting NLPHL in fresh tissue samples, most of which would have otherwise been labeled as nondiagnostic or reactive lymphoid processes.

Prostate cancer (PCa) is estimated to be the malignancy with the highest incidence in men in 2020, both in the United States and in Europe, (1,2) being the second leading [...], * Context.--There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.--To evaluate the clinical utility of [-2]proprostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.--Two hundred thirty-seven men (PSA: 2-10 ng/ mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.--Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: [greater than or equal to] 1.25%) and PHI (cutoff: [greater than or equal to] 27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: [greater than or equal to] 1.12% and [greater than or equal to] 24 for %[-2]proPSA and PHI, respectively). Conclusions.--The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.

Antigen platforms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing have rapid turnaround time, are easy to use, and are less expensive than real-time reverse transcription PCR (RT-PCR) [...]

Deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have raised concerns that contact with the corpses of deceased persons might pose a risk for transmitting infection (1). Nasopharyngeal [...]

Accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for patient management and infection control (1). Molecular diagnostics are highly sensitive in the acute phase of [...]

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), the virus that causes COVID-19, was first detected in Wuhan, China in December 2019 and has quickly led to a global pandemic on [...], * Context.--The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has elicited a surge in demand for serologic testing to identify previously infected individuals. In particular, antibody testing is crucial in identifying COVID-19 convalescent plasma, which has been approved by the Food and Drug Administration under the Emergency Use Authorization for use as passive immunotherapy for hospitalized patients infected with COVID-19. Currently, high-titer COVID-19 convalescent plasma can be qualified by Ortho&apos;s Vitros COVID-19 IgG antibody test. Objective.--To explore the use of an efficient testing method to identify high-titer COVID-19 convalescent plasma for use in treating COVID-19-infected patients and track COVID-19 positivity over time. Design.--We evaluated an enzyme-linked immunosorbent assay (ELISA)-based method that detects antibodies specific to the SARS-CoV-2 receptor binding domain (RBD) with individual and pooled plasma samples and compared its performance against the Vitros COVID-19 IgG antibody test. Using the pooled RBD-ELISA (P-RE) method, we also screened more than 10 000 longitudinal healthy blood donor samples to assess seroprevalence. Results.--P-RE demonstrates 100% sensitivity in detecting Food and Drug Administration-defined high-titer samples when compared with the Vitros COVID-19 IgG antibody test. Overall sensitivity of P-RE when compared with the Vitros COVID-19 IgG antibody test and our individual sample RBD-ELISA (I-RE) were 83% and 56%, respectively. When screening 10 218 healthy blood donor samples by P-RE, we found the seroprevalence correlated with the local infection rates with a correlation coefficient of 0.21 (P < .001). Conclusions.--Pooling plasma samples can be used to efficiently screen large populations for individuals with high-titer anti-RBD antibodies, important for COVID-19 convalescent plasma identification. doi: 10.5858/arpa.2021-0215-SA

With the availability of vaccines against the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as the pressure to reopen the economy increases, the demand for coronavirus disease [...], * Context.--Emerging evidence shows correlation between the presence of neutralization antibodies (nAbs) and protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently available commercial serology assays lack the ability to specifically identify nAbs. An enzyme-linked immunosorbent assay-based nAb assay (GenScript cPass neutralization antibody assay) has recently received emergency use authorization from the Food and Drug Administration. Objective.--To evaluate the performance characteristics of this assay and compare and correlate it with the commercial assays that detect SARS-CoV-2-specific immunoglobulin G (IgG). Design.--Specimens from SARS-COV-2 infected patients (n = 124), healthy donors obtained prepandemic (n = 100), and patients with non-coronavirus disease 2019 (COVID-19) respiratory infections (n = 92) were analyzed using this assay. Samples with residual volume were also tested on 3 commercial serology platforms (Abbott, Euroimmun, Siemens). Twenty-eight randomly selected specimens from patients with COVID-19 and 10 healthy controls were subjected to a plaque reduction neutralization test. Results.--The cPass assay exhibited 96.1% (95% CI, 94.9%-97.3%) sensitivity (at PCR), 100% (95% CI, 98.0%-100.0%) specificity, and zero cross-reactivity for the presence of non-COVID-19 respiratory infections. When compared with the plaque reduction assay, 97.4% (95% CI, 96.2%-98.5%) qualitative agreement and a positive correlation ([R.sup.2] = 0.76) was observed. Comparison of IgG signals from each of the commercial assays with the nAb results from plaque reduction neutralization test/cPass assays displayed greater than 94.7% qualitative agreement and correlations with [R.sup.2] = 0.43/0.68 (Abbott), [R.sup.2] = 0.57/0.85 (Euroimmun), and [R.sup.2] = 0.39/0.63 (Siemens), respectively. Conclusions.--The combined data support the use of cPass assay for accurate detection of the nAb response. Positive IgG results from commercial assays associated reasonably with nAbs presence and can serve as a substitute. doi: 10.5858/arpa.2021-0213-SA

Tests for antibodies to nuclear antigens (ANAs) are important for clinical diagnosis of several autoimmune rheumatic diseases, are central to epidemiologic classification of systemic lupus erythematosus and subsets of systemic [...], Context.--Presence of antibodies to nuclear antigens (ANAs) above a threshold titer is an important diagnostic feature of several autoimmune diseases, yet titers reported vary between laboratories. Proficiency survey results can help clarify factors contributing to the variability. Objective.--To determine the contribution of HEp-2 ANA kits from different manufacturers to the variation in titers, and assess whether the differences between kits are consistent over the long term. Design.--HEp-2 ANA titers reported by laboratories participating in the external quality assessment proficiency testing surveys conducted by the College of American Pathologists between 2008 and 2018 were analyzed. The ANA titers reported for each specimen were ranked according to the kits being used by testing laboratories, and the statistical significance of the differences was determined. Results.--The ANA titer results were strongly influenced by the HEp-2 ANA kit used (P < .001). During the 11 years studied, the rank order of the ANA titer for each kit relative to the other kits was remarkably consistent. The rank of ANA titer for individual ANA patterns observed for each kit was similar to the overall rank of that kit. Conclusions.--Variability in ANA titers was strongly associated with the kits used, and the differences between kits were quite consistent during the 11 years studied. Because the variability is not random, it has the potential to be managed by harmonizing kits, which could lead to improved consistency in reporting ANA titers. doi: 10.5858/arpa.2020-0419-CP

The global pandemic of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already infected more than 113 million individuals globally, with the United States [...], Context.--Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) testing is used for serosurveillance and will be important to evaluate vaccination status. Given the urgency to release coronavirus disease 2019 (COVID-19) serology tests, most manufacturers have developed qualitative tests. Objective.--To evaluate clinical performance of 6 different SARS-CoV-2 IgG assays and their quantitative results to better elucidate the clinical role of serology testing in COVID-19. Design.--Six SARS-CoV-2 IgG assays were tested using remnant specimens from 190 patients. Sensitivity and specificity were evaluated for each assay with the current manufacturer&apos;s cutoff and a lower cutoff. A numeric result analysis and discrepancy analysis were performed. Results.--Specificity was higher than 93% for all assays, and sensitivity was higher than 80% for all assays ([greater than or equal to]7 days post-polymerase chain reaction testing). Inpatients with more severe disease had higher numeric values compared with health care workers with mild or moderate disease. Several discrepant serology results were those just below the manufacturers&apos; cutoff. Conclusions.--Severe acute respiratory syndrome coronavirus 2 IgG antibody testing can aid in the diagnosis of COVID-19, especially with negative polymerase chain reaction. Quantitative COVID-19 IgG results are important to better understand the immunologic response and disease course of this novel virus and to assess immunity as part of future vaccination programs. doi: 10.5858/arpa.2020-0851-SA

Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to prevent viral dissemination. Rapid antigen tests (RATs) have recently been approved and are now widely used in [...]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged >1 year ago (1) but still keeps a strong grip not only on daily life but also on diagnostic capacities. Reverse transcription [...]

The COVID-19 pandemic resulted in a significant expansion of infectious diseases testing technology. (1) As of November 2021, the US Food and Drug Administration (FDA) has conferred emergency use authorization [...]

1 | INTRODUCTION HIV viral load (VL) monitoring is recommended by the World Health Organization (WHO) to confirm viral suppression and to take action if a patient has an elevated [...], Introduction: In many low- and middle-income countries, HIV viral load (VL) testing occurs at centralized laboratories and time-to-result-delivery is lengthy, preventing timely monitoring of HIV treatment adherence. Near point-of-care (POC) devices, which are placed within health facility laboratories rather than clinics themselves (i.e. "true" POC), can offer VL in conjunction with centralized laboratories to expedite clinical decision making and improve outcomes, especially for patients at high risk of treatment failure. We assessed impacts of near-POC VL testing on result receipt and clinical action in public sector programmes in Cameroon, Democratic Republic of Congo, Kenya, Malawi, Senegal, Tanzania and Zimbabwe. Methods: Routine health data were collected retrospectively after introducing near-POC VL testing at 57 public sector health facilities (2017 to 2019, country-dependent). Where possible, key indicators were compared to data from patients receiving centralized laboratory testing using hazard ratios and the Somers&apos; D test. Results: Data were collected from 6795 tests conducted on near-POC and 17614 tests on centralized laboratory-based platforms. Thirty-one percent (2062/6694) of near-POC tests were conducted for high-risk populations: pregnant and breastfeeding women, children and those with suspected failure. Compared to conventional testing, near-POC improved the median time from sample collection to return of results to patient [six vs. sixty-eight days, effect size: -32.2%; 95% CI: -41.0% to -23.4%] and to clinical action for individuals with an elevated HIV VL [three vs. fourty-nine days, effect size: -35.4%; 95% CI: -46.0% to -24.8%]. Near-POC VL results were two times more likely to be returned to the patient within 90 days compared to centralized tests [50% (1781/3594) vs. 27% (4172/15271); aHR: 2.22, 95% CI: 2.05 to 2.39]. Thirty-seven percent (340/925) of patients with an elevated near-POC HIV VL result had documented clinical follow-up actions within 30 days compared to 7% (167/2276) for centralized testing. Conclusions: Near-POC VL testing enabled rapid test result delivery for high-risk populations and led to significant improvements in the timeliness of patient result receipt compared to centralized testing. While there was some improvement in time-to-clinical action with near-POC VL testing, major gaps remained. Strengthening of systems supporting the utilization of results for patient management are needed to truly capitalize on the benefits of decentralized testing. Keywords: point of care; viral load monitoring; Africa; viral suppression

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), the cause of the coronavirus disease 2019 (COVID-19) pandemic, is spreading throughout the world. (1) More than 1 699 000 confirmed cases and [...], * Context.--Covert severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could be seeding new outbreaks. How to identify asymptomatic SARS-CoV2 infections early has become a global focus. Objective.--To explore the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies detection, nucleic acid tests, and computed tomography (CT) scanning to identify asymptomatic SARS-CoV-2 infection. Design.--The clinical data of 389 individuals with close contacts, including in general characteristics, SARS-CoV-2 etiology, serum-specific IgM and IgG antibody detection and CT imaging results, were systematically analyzed. Results.--The present study showed that only 89 of 389 individuals with close contacts were positive after the first nucleic acid test, while 300 individuals were still negative after 2 nucleic acid tests. Among the 300 individuals, 75 did not have pneumonia, and the other 225 individuals had pulmonary imaging changes. A total of 143 individuals were eventually diagnosed as having asymptomatic infection through IgM antibody and IgG antibody detection. The sensitivity, specificity, and false-negative rate of IgM and IgG antibody detection were approximately 97.1% (347 of 357), 95.3% (204 of 214), and 4.67% (10 of 214), respectively. It also indicated that during approximately 2 weeks, most individuals were both IgM positive and IgG positive, accounting for 68.57% (72 of 105). During approximately 3 weeks, the proportion of IgM-positive and IgG-positive individuals decreased to 8.57% (9 of 105), and the proportion of IgM-negative and IgG-positive individuals increased to 76.19% (80 of 105). Conclusions.--There are highlighted prospects of IgM/ IgG antibody detection as a preferred method in identifying the individuals with asymptomatic SARS-CoV-2 infection, especially combined with nucleic acid tests and pulmonary CT scanning. (Arch Pathol Lab Med. 2021;145:39-45; doi: 10.5858/arpa.2020-0310-SA)

Coronavirus disease (COVID-19) emerged in December 2019 (1,2), and by June 2020, [approximately equal to]10 million persons worldwide had acquired the disease. The confirmatory test for severe acute respiratory syndrome [...]

Author(s): Quan-Xin Long [sup.1] , Xiao-Jun Tang [sup.2] , Qiu-Lin Shi [sup.2] , Qin Li [sup.3] , Hai-Jun Deng [sup.1] , Jun Yuan [sup.1] , Jie-Li Hu [sup.1] , Wei [...], The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People&apos;s Hospital for centralized isolation in accordance with policy.sup.1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys. A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.

Author(s): Lukas E. Brümmer 1, Stephan Katzenschlager 2, Sean McGrath 3, Stephani Schmitz 4, Mary Gaeddert 1, Christian Erdmann 5, Marc Bota 6, Maurizio Grilli 7, Jan Larmann 2, Markus [...], Background Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched preprint and peer-reviewed databases for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariable mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1). When manufacturer instructions were followed, sensitivity increased to 76.3% (95% CI 73.7 to 78.7). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values Conclusions Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all (>90%) when high viral loads are present. With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.

Author(s): Giorgia Guglielmi Author Affiliations: Fast coronavirus tests: what they can and can't do Health-care workers test a resident of Mumbai, India, for coronavirus infection using a rapid antigen assay. [...], Rapid antigen tests are designed to tell in a few minutes whether someone is infectious. Will they be game changers? Fast coronavirus tests: what they can and can&apos;t do Rapid antigen tests are designed to tell in a few minutes whether someone is infectious. Will they be game changers?

We are concerned that the approved rapid antigen tests (RATs) used in Australia to detect SARS‐CoV‐2, which causes COVID‐19 infection, are being used for a purpose for which they were [...]