No abstract

Background Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates. Methodology/Principal findings This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5–86.9) using the titre cut off >1:20 and 83.9% (82.2–85.6), 70.2% (68.1–72.5) and 54.2% (52.0–56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0–89.2], >1:160, 74.4% [67.5–79.7]) than those with mild presentation (56.7% [49.9–62.9] and 44.1% [37.3–50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9–39.2] and 10.0% [3.7–20.1], respectively). IgG and neutralising antibody levels correlated poorly. Conclusions/Significance 85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.

Background Rapid diagnostic tests (RDTs) developed for point of care detection of SARS-CoV-2 antigen are recommended by WHO to use trained health care workers to collect samples. We hypothesised that self-taken samples are non-inferior for use with RDTs to diagnose COVID-19. We designed a prospective diagnostic evaluation comparing self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform RDTs for SARS-CoV-2, and how these compare to RT-PCR. Methods Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited at the NHS Test and Trace drive-through community PCR testing site (Liverpool, UK); one withdrew before analysis. Self-administered throat/nasal swab for the Covios® RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT were collected. RDT results were compared to RT-PCR, as the reference standard, to calculate sensitivity and specificity. Findings Seventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9–97.2), compared to 78.4% (58/74, 95% CI: 69.0–87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7–19.6, p = 0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3–100.0), versus 98.9% (172/174, 95% CI: 97.3–100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5–1.7, p = 0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7–100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1–100.0) were not significantly different (p = 0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2–98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5–95.5, p = 0.003). Interpretation In conclusion, self-taken swabs for COVID-19 testing offer an accurate alternative to healthcare worker taken swabs for use with RDTs. Our results demonstrate that, with no training, self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. This is especially important where the lack of trained healthcare workers restricts access to testing.

In the context of the coronavirus disease 2019 (COVID-19) pandemic there has been an increase of the use of antigen-detection rapid diagnostic tests (Ag-RDT). The performance of Ag-RDT vary greatly between manufacturers and evaluating their analytical limit of detection (LOD) has become high priority. Here we describe a manufacturer-independent evaluation of the LOD of 19 marketed Ag-RDT using live SARS-CoV-2 spiked in different matrices: direct culture supernatant, a dry swab, and a swab in Amies. Additionally, the LOD using dry swab was investigated after 7-days storage at -80C of the SARS-CoV-2 serial dilutions. An LOD of ≈ 5.0 x 10^2 pfu/ml (1.0 x 10^6 genome copies/ml) in culture media is defined as acceptable by the World Health Organization. Fourteen of nineteen Ag-RDTs (ActiveXpress, Espline, Excalibur, Innova, Joysbio, Mologic, NowCheck, Orient, PanBio, RespiStrip, Roche, Standard-F, Standard-Q and Sure-Status) exceeded this performance criteria using direct culture supernatant applied to the Ag-RDT. Six Ag-RDT were not compatible with Amies media and a decreased sensitivity of 2 to 20-fold was observed for eleven tests on the stored dilutions at -80C for 7 days. Here, we provide analytical sensitivity data to guide appropriate test and sample type selection for use and for future Ag-RDT evaluations.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%–98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%–100% specificity and 27%–31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Background There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs. Methods Sera from 100 SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) positive participants were recruited through the FASTER study. A total of 105 pre-pandemic sera from participants with other infections were included as negative samples. Results At presentation sensitivity against RT-PCR ranged from 37.4-79% for IgM/IgG, 30.3-74% for IgG, and 21.2-67% for IgM. Sensitivity for IgM/IgG improved ≥21 days post symptom onset for 10/12 tests. Specificity ranged from 74.3-99.1% for IgM/IgG, 82.9-100% for IgG, and 75.2-98% for IgM. Compared to the EuroImmun IgG enzyme-linked immunosorbent assay (ELISA), sensitivity and specificity ranged from 44.6-95.4% and 85.4-100%, respectively. Conclusion There are many LFAs available with varied sensitivity and specificity. Understanding the diagnostic accuracy of these tests will be vital as we come to rely more on the antibody status of a person moving forward, and as such manufacturer-independent evaluations are crucial.

No abstract

In the UK, approximately 40 per cent of the pig breeding herds are outdoors. To monitor their porcine reproductive and respiratory syndrome virus (PRRSV) status, blood is collected commonly from piglets around weaning. Sample collection in British outdoor pigs often occurs during the early morning hours when the piglets tend to accumulate inside sheltered areas. For practical reasons, dry cotton swabs are occasionally used for blood collection and stored at room temperature until arrival in the laboratory. Detection of PRRSV RNA is a function of viral concentration, sample type and storage condition. To evaluate a possible impact of the sampling protocol on PRRSV1 detection, experimentally spiked blood samples using three dilutions of a representative PRRSV1 strain were prepared. In addition, blood samples from pigs naturally infected with PRRSV were obtained from a PRRSV-positive British herd. Spiked blood and blood from infected pigs were used to obtain sera, dry or wet (immersed in saline) polyester or cotton swabs and FTA cards. The different samples were stored for 24 hours, 48 hours or 7 days at 4°C or 20°C and tested by a real-time reverse transcriptase PRRSV PCR assay. Under the study conditions, the best matrix was serum (96.7 per cent), followed by wet swabs (78 per cent), dry swabs (61.3 per cent) and FTA cards (51 per cent). Polyester swabs (76 per cent) showed a better performance than cotton swabs (63.3 per cent). The reduction in sensitivity obtained for swabs and FTA cards was particularly high at low viral concentrations. The results indicate that wet polyester swabs should be used whenever possible.