The QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay for rapid detection of COVID-19 at point-of-care: preliminary evaluation of a novel technology (preprint)

Background: Accurate, affordable, and rapid point-of-care (PoC) diagnostics are critical to the global control and management of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR). Here, we report a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS CoV-2 RT-PCR assay. Methods: Between November 2020 and March 2021, we obtained 49 longitudinal nose and throat swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 at St Georges' NHS Foundation Trust, London (UK). In addition, we obtained 101 mid nasal swabs from healthy volunteers in June 2021. We then used these samples to evaluate the Q-POC SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC test against a reference laboratory-based RT-PCR assay. Results: The overall sensitivity of the Q-POC test compared with the reference test was 96.88% (83.78%- 99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35% to 90.95% CI) without altering the reference test's Ct cut-off value of 40. Conclusions: The Q-POC test is a sensitive, specific and rapid point-of-care test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC test provides an accurate and afforda-ble option for RT-PCR at point-of-care without the need for sample pre-processing and laboratory handling. The Q-POC test would enable rapid diagnosis and clinical triage in acute care and other settings.

Immunoglobulin-G Enzyme-Linked Immunosorbent Assay Predicts Neutralising Antibody Response in Convalescent SARS-CoV-2 Patients (preprint)

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb but are not amenable to mass testing as they take several days and require use of viable SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 (S1) and nucleocapsid protein (NP) at predicting the presence and magnitude of NAb determined by PRNT. SARS-CoV-2 IgG ELISA correlated well with NAb and was highly sensitive (93.8% [95% CI 79.2–99.2]) and specific (88.9% [95% CI 51.8–99.7%]) at predicting the presence of NAb. There was not a strong correlation between IgM ELISA and PRNT result. IgG ELISA provides a useful, high throughput method of predicting the presence of neutralising antibodies, with higher ELISA results increasing the likelihood of having a greater NAb titre.

Self-sampling of capillary blood for serological testing of SARS-CoV-2 by COVID-19 IgG ELISA (preprint)

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty seven out of thirty eight participants were able to self-collect an adequate sample of capillary blood ([≥]50 l). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen's kappa coefficient of >0.88 (near-perfect agreement). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections (preprint)

We report dynamics of seroconversion to SARS-CoV-2 infections detected by IgG ELISA in 177 individuals diagnosed by RT-PCR. Longitudinal analysis identifies 2-8.5% of individuals who do not seroconvert even weeks after infection. They are younger than seroconverters who have increased co-morbidity and higher inflammatory markers such as C-Reactive Protein. Higher antibody responses are associated with non-white ethnicity. Antibody responses do not decline during follow up almost to 2 months. Serological assays increase understanding of disease severity. Their application in regular surveillance will clarify the duration and protective nature of humoral responses to SARS-CoV-2.

St George's COVID shield for use by ENT surgeons performing tracheostomies (preprint)

Healthcare workers are at increased risk of exposure to COVID-19. The majority of cases are acquired through inhalation of infected respiratory particles, contamination with infected surfaces or whilst performing aerosol-generating procedures. Basic infection prevention measures are essential to protect healthcare workers from contracting the disease when managing patients; consequently global demand for personal protective equipment (PPE) has exceeded supply in many regions. We present a novel, innovative polycarbonate shield designed for ENT clinicians performing tracheostomies. Clinical investigations using the shield demonstrated a sixteen-fold decrease in the number of particles detected at the position of the operating surgeon when the shield was used (particle size 0.3m; with shield 27,000 versus 439,000 without shield). The shield, used with appropriate PPE, could therefore help to minimise exposure to aerosol generated particles such as during tracheostomies on patients with COVID-19.

Rapid development of COVID-19 rapid diagnostics for low resource settings: accelerating delivery through transparency, responsiveness, and open collaboration (preprint)

In January, Mologic, embarked on a product development pathway for COVID-19 diagnostics focusing on ELISA and rapid diagnostic tests (RDTs), with anticipated funding from Wellcome Trust and DFID. 755 clinical samples from known COVID-19 patients and hospital negative controls were tested on Mologics IgG ELISA. The reported sensitivity on 191 SGUL prospectively enrolled patients was 95% on day 7 or more post diagnosis, and 97% 10 days or more post-diagnosis. A specificity panel comprising 564 samples pre-December 2019 were tested to include most common respiratory pathogens, other types of coronavirus, and flaviviruses. Specificity in this panel was 97%. This is the first in a series of Mologic products for COVID-19, which will be deployed for COVID-19 diagnosis, contact tracing and sero-epidemiological studies to estimate disease burden and transmission with a focus on ensuring access, affordability, and availability to lowest resource settings.