Comparison Of New and emerging SARS-CoV-2 variant Transmissibility through Active Contact Testing. A comparative cross-sectional household seroprevalence study. (preprint)

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts, this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding.

Childhood listening and associated cognitive difficulties persist into adolescence (preprint)

Our objective in this study was to examine children with and without listening difficulty (LiD) longitudinally to ask whether LiD was developmentally transient or persistent. Like many other developmental problems, we hypothesized that LiD persists into adolescence. Behavioral and physiological data were collected from children initially aged 6-13 years at baseline and two and four years later. Of 169 enrolled participants, 147, 100, and 31 children completed required testing in study visits at baseline, 2 years, and 4 years later, respectively. All children had clinically normal audiograms at all visits. Listening skills scores from a caregiver report scale (ECLiPS), and auditory and cognitive skills were significantly poorer in the LiD group than in a typically developing (TD) group throughout the study period. In both groups, age-adjusted listening and auditory skills increased over time. Using the longitudinal data, a parsimonious prediction model for ECLIPS scores (pooled across groups) was created. The final model included maternal education, spatial listening skills, and cognitive performance, which explained 54.8% of the variance in the ECLiPS score. Children with LiD but normal audiograms have, relative to TD children, persistent listening difficulties, challenges in competing speech tasks, and poor cognitive performance through adolescence. The degree of LiD can be independently predicted by maternal education, cognitive performance, and spatial listening skills. Research highlights Children aged 6-13 years with clinically normal audiograms are often reported by their caregivers to have listening difficulties In a four-year longitudinal evaluation, children with listening difficulties were found to have persistent challenges in competing speech segregation and generally poor cognitive performance Maternal education, spatial segregation of speech, and cognitive performance independently predicted the degree of the children’s listening difficulties

Remote self-report and speech-in-noise measures predict clinical audiometric thresholds (preprint)

The COVID-19 pandemic highlighted the need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab testing. Digits-in-noise (DIN) is a reliable speech-in-noise test that can be self-administered remotely. This study investigated the predictive validity of a self-administered DIN test and a commonly used self-report, the speech, spatial, and qualities of hearing (SSQ-12), for lab-based, supervised DIN and audiometry. Speech reception thresholds (SRTs) of 34 adults (18-64 y/o), 16 normal-hearing (NH) and 18 hearing-impaired (HI), were measured at home (remote-DIN) and in the lab (lab-DIN). All DIN testing used English digits 0-9, binaurally presented as triplets in different speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz). Audiometry was administered during lab testing. An SSQ-12 e-version was completed by participants at home. As expected, NH listeners had significantly higher SSQ scores, and remote- and lab-DIN SRTs than HI listeners. All test versions of DIN were significantly correlated with pure-tone-average (PTA), with the 2-kHz filtered test the best predictor, explaining 50% of variance in PTA. SSQ also significantly predicted PTA. Overall, DIN-SRTs were better predictors of audiograms than the SSQ. Remote-DIN correlated significantly with lab-DIN, and there was no significant mean difference between remote- and lab-DIN. Test-retest reliability was measured for broadband remote-DIN. High, significant intraclass correlation coefficients indicated strong internal consistency of the remote-DIN. This study shows that remote SSQ-12 and DIN are valid screening tools for capturing important aspects of auditory function.

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa (preprint)

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and death was judged SARS-CoV-2 related by attending physician. Findings: 315,570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3,548,738 tests and 1.6% of all children in the country. Of children tested, 46,137 (14.6%) were positive. Children made up 2.9% (n=2,007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals (CI) 1.08 - 4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28 -18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01 -12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years and those with underlying conditions should be considered for increased testing and vaccination.

Improving the prehospital identification and management of people presenting to the ambulance service with COVID 19 symptoms

BackgroundLittle is known about how patients with COVID-19 present to ambulance services or their outcomes. Between 1st March and 31st August 2020 we investigated individuals who called the Scottish Ambulance Service (SAS) with COVID-19 symptoms and those that were later tested COVID-19 positive. We analysed i) their demographic and clinical characteristics;ii) their disposal;and iii) their admission and mortality outcomes.MethodsSAS and NHS Scotland Health Board data are routinely linked in a national database. These data evidence a patients journey from ambulance call to hospital attendance and subsequent outcome. Evidence of COVID-19 testing was identified 10 days either side of the call.Results171,169 patients made 257,207 calls during the study period. Of these, 2.8% (n=7,305) were categorised as possible COVID-19 patients during telephone triage. From the flagged +ve patient calls 6% had a COVID-19 positive result, 29% had a negative COVID-19 result and the other 65% had no evidence of being tested. The majority (54%) were taken to the Emergency Department;73% received further hospital care. The proportion of patient calls admitted within 10 days of the call was 31% for those not conveyed against 82% for conveyed. Final prehospital physiology for COVID-19 positive patients demonstrated lower oxygen saturations, higher respiratory rates and temperatures. 4.9% and 11.7% of patients conveyed to hospital died within 3 and 30 days vs 5.2% and 19.6% of patients not conveyed respectively.ConclusionsThis study suggests telephone triage is not a reliable identifier of COVID-19 patients reinforcing existing requirements for Personal Protective Equipment. 30-day mortality rates differed between those patients initially conveyed vs not conveyed. Clinical characteristics of COVID-19 positive patients suggest they were clinically less well than other patients.

SARS-CoV-2 Infection Among Healthcare Workers in South Africa: A Longitudinal Cohort Study (preprint)

Background: Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection. We investigated the burden of SARS-CoV-2 infection in a longitudinal cohort of frontline HCWs in South Africa from April to September 2020.Methods: HCWs working in five departments at Chris Hani Baragwanath Academic Hospital were followed-up weekly, independent of clinical symptomatology, during the first wave of the COVID-19 pandemic and tested for SARS-CoV-2 infection by polymerase chain reaction (PCR). Furthermore, paired sera collected at enrolment and end of surveillance were tested for IgG to receptor binding domain of the spike protein to evaluate for sero-response.Findings: Overall 137 (34·6%) of 396 enrolled HCWs had PCR-confirmed SARS-CoV-2 infection (132·1 [95%CI: 111·8, 156·2] per 1,000 person-months), and an additional 27 only showed sero-response at the end of follow-up. HCWs in the Internal Medicine department had the highest rate of SARS-CoV-2 infection (61·7%; 103/167), with HCWs from other departments (27·5%; 63/229) experiencing 70% lower odds of infection (adjust odds ratio 0·29 [95%CI: 0·17, 0·49]) in multivariable analysis. Among SARS-CoV-2 PCR-confirmed cases, 14 (10·4%) HCWs remained asymptomatic, 41 (30·4%) were pre-symptomatic and 80 (59·3%) were symptomatic. Symptomatic cases compared to asymptomatic had lower PCR cycle threshold values at diagnosis (24·2 vs. 28·9) and longer duration of PCR-positivity (18·9 vs. 13·0 days).Interpretation: The high rates of SARS-CoV-2 infection among HCWs in a relatively well-resourced middle-income setting attest to the threat that the COVID-19 pandemic poses to health care systems.Funding: This study was supported by the European & Developing Countries Clinical Trials Partnership (grant number RIA2020EF-3020) and The Bill & Melinda Gates Foundation (grant number INV018148_2020). There was also partial support from the Department of Science and Technology and National Research Foundation: South African Research Chair Initiative in Vaccine Preventable Diseases; and the South African Medical Research Council.Conflict of Interest: MCN has received grant support from the Bill & Melinda Gates Foundation, MedImmune and Pfizer outside the submitted work; has received honoraria from Pfizer and Sanofi Pasteur outside the submitted work. CLC has received grant support from the Bill & Melinda Gates Foundation, Pfizer and IMPRINT outside the submitted work; has received honoraria from Pfizer outside the submitted work. SAM has received grant support from the Bill & Melinda Gates Foundation, Pfizer, GlaxoSmithKline, Minervax and Novavx outside the submitted work; personal fees from Bill & Melinda Gates Foundation outside the submitted work. All other authors have nothing to disclose.Ethical Approval: The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (reference number 200405) and conducted in accordance with Good Clinical Practice guidelines. All study participants provided written informed consent.

A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection (preprint)

With the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, there is need for sensitive, specific and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR, with many commercial kits now available for this purpose. However, these are expensive and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside internal controls that monitor sample quality and nucleic acid extraction efficiency. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by nose-and-throat swabbing. The inclusion of a human control probe in our assay provides additional information that could help reduce false negative rates.

Standard operating procedures for SARS-CoV-2 detection by a clinical diagnostic RT-LAMP assay (preprint)

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 40,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated standard operating procedure (SOP) for high-throughput SARS- CoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

Scalable and Resilient SARS-CoV2 testing in an Academic Centre (preprint)

The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.