SARS-CoV-2 testing of 11,884 healthcare workers at an acute NHS hospital trust in England: a retrospective analysis

Healthcare workers (HCWs) are known to be at increased risk of infection with SARS-CoV-2, although whether these risks are equal across all roles is uncertain. Here we report a retrospective analysis of a large real-world dataset obtained from 10 March to 6 July 2020 in an NHS Foundation Trust in England with 17,126 employees. 3,338 HCWs underwent symptomatic PCR testing (14.4% positive, 2.8% of all staff) and 11,103 HCWs underwent serological testing for SARS-CoV-2 IgG (8.4% positive, 5.5% of all staff). Seropositivity was lower than other hospital settings in England but higher than community estimates. Increased test positivity rates were observed in HCWs from BAME backgrounds and residents in areas of higher social deprivation. A logistic regression model adjusting for these factors showed significant increases in the odds of testing positive in certain occupational groups, most notably domestic services staff, nurses and health-care assistants. PCR testing of symptomatic HCWs appeared to underestimate overall infection levels, probably due to asymptomatic seroconversion. Clinical outcomes were reassuring, with only a small minority of HCWs with COVID-19 requiring hospitalisation (2.3%) or ICU management (0.7%) and with no deaths. Despite a relatively low level of HCW infection compared to other UK cohorts, there were nevertheless important differences in test positivity rates between occupational groups, robust to adjustment for demographic factors such as ethnic background and social deprivation. Quantitative and qualitative studies are needed to better understand the factors contributing to this risk. Robust informatics solutions for HCW exposure data are essential to inform occupational monitoring.

Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory

CD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in the current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific CD8+ T cells are detectable in the majority of individuals recovering from SARS-CoV-2 infection. However, optimal virus-specific epitopes, the role of pre-existing heterologous immunity as well as their kinetics and differentiation program during disease control have not been defined in detail. Here, we show that both pre-existing and newly induced SARS-CoV-2-specific CD8+ T-cell responses are potentially important determinants of immune protection in mild SARS-CoV-2 infection. In particular, our results can be summarized as follows: First, immunodominant SARS-CoV-2-specific CD8+ T-cell epitopes are targeted in the majority of individuals with convalescent SARS-CoV-2 infection. Second, MHC class I tetramer analyses revealed the emergence of phenotypically diverse and functionally competent pre-existing and newly induced SARS-CoV-2-specific memory CD8+ T cells that showed similar characteristics compared to influenza-specific CD8+ T cells. Third, SARS-CoV-2-specific CD8+ T-cell responses are more robustly detectable than antibodies against the SARS-CoV-2-spike protein. This was confirmed in a longitudinal analysis of acute-resolving infection that demonstrated rapid induction of the SARS-CoV-2-specific CD8+ T cells within a week followed by a prolonged contraction phase that outlasted the waning humoral immune response indicating that CD8+ T-cell responses might serve as a more precise correlate of antiviral immunity than antibody measurements after convalescence. Collectively, these data provide new insights into the fine specificity, heterogeneity, and dynamics of SARS-CoV-2-specific memory CD8+ T cells, potentially informing the rational development of a protective vaccine against SARS-CoV-2.

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

ABSTRACTSARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.Competing Interest StatementThe authors have declared no competing interest.View Full Text

COVID-19 management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases centre: a detailed descriptive analysis

BackgroundRecent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is little granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on clinical decisions and patient journeys. MethodsWe retrospectively analysed the management and 28-day outcomes of 316 consecutive adult patients with SARS-CoV-2 PCR-confirmed COVID-19 admitted to a large NHS Foundation Trust with a tertiary High Consequence Infectious Diseases centre in the North of England. FindingsMost patients were elderly (median age 75) with multiple comorbidities. One quarter were admitted from residential or nursing care. Symptoms were consistent with COVID-19, with cough, fever and/or breathlessness in 90.5% of patients. Two thirds of patients had severe disease on admission. Mortality was 81/291 (27.8%). Most deaths were anticipated; decisions to initiate respiratory support were individualised after consideration of patient wishes, premorbid frailty and comorbidities, with specialist palliative care input where appropriate. 22/291 (7.6%) patients were intubated and 11/22 (50%) survived beyond discharge. Multiple logistic regression identified age as the most significant risk factor for death (OR 1.09 [95% CI 1.06 - 1.12] per year increase, p < 0.001). InterpretationThese findings provide important clinical context to outcome data. Deaths were anticipated, occurring in patients with advance decisions on ceilings of treatment. Age was the most significant risk factor for death, confirming that demographic factors in the population are a major influence on hospital mortality rates. FundingFunding was not required.

A novel computer-based method for the measurement of the lipid "load" in the coronary vessels of rabbits.

INTRODUCTION: This study reports the development of a new, accurate and reproducible method which combines histological and computer techniques for the determination of fatty load in cholesterol-fed rabbits. METHODS: New Zealand male rabbits were randomly divided into three groups. The animals in group 1 (control) received neither cholesterol nor drugs. Those in group 2 received a 2% cholesterol diet for 30 days, followed by a normal diet for 45 days. In addition during the latter period (day 31 to day 75) animals received 200 g of chopped carrots each morning. The rabbits in group 3 followed the same dietary regime as those in group 2 except that 8.36 mg of simvastatin and 1.76 g cholestyramine were mixed with their carrots. On the 76th day, the animals were sacrificed and their blood and hearts were collected. Histological sections (15 microm thick) of hearts were cut at 90 degrees to the long axis using a motorized freezing microtome. Every tenth section was mounted on a glass slide and stained with Oil Red O. A total of hundred slides prepared from each heart were scanned into a computer and the area stained by Oil Red O was measured, giving a measure of the total fatty "load" in each heart. RESULTS: There was a highly significant increase in the coronary fatty deposits in the hearts of the animals fed with cholesterol rich diet (group 2) as compared to the control rabbits in group 1. Treatment of rabbits with simvastatin plus cholestyramine (group 3) significantly reduced the coronary lipids load. DISCUSSION: The combination of histological and computer-based techniques used in this study provides an accurate and reproducible method for the quantitation of fatty deposits in rabbit coronary vessels. This report is based on the measurement of coronary lipid depositions rather than aortic lesions. It also overcomes the shortcoming of the majority of the earlier published methods which are generally limited to the measurement of fatty plaques in only few major coronary vessels, totally neglecting the many small distributive vessels which are often responsible for cardiac ischemic disease.

Anesthesia care for living-related liver transplantation for infants and children with end-stage liver disease: report of our initial experience.

STUDY OBJECTIVE: To describe our initial experience of the perioperative anesthetic care provided to pediatric recipients during living-related liver transplantation. DESIGN: Cohort review of the perioperative anesthetic care for living-related liver transplantation. SETTING: Tertiary referral and postgraduate teaching hospital. PATIENTS: 27 children (20 males, 7 females) with end-stage hereditary metabolic liver disease requiring living-related liver transplantation. INTERVENTION: Perioperative care was administered during living-related liver transplantation. MEASUREMENTS: The major intraoperative physiologic events and concerns are described, as well as the anesthesia technique for pediatric living-related liver transplantation anesthesia. Intraoperative changes in physiologic parameters and the intraoperative requirements in our series are also reported. MAIN RESULTS: During a 30-month period, 27 children (20 males and 7 females) were scheduled for transplantation with an hepatic graft from a living-related donor. Twenty-six children received a graft from a living-related donor, and one was retransplanted with a cadaveric graft because of graft failure, and one child received a cadaveric graft because of the lack of a suitable donor. All patients received intravenous (IV) anesthesia with fentanyl, midazolam, and cisatracurium, and were ventilated with oxygen/air. Mean induction and presurgical preparation time was 1.18 hours, with a surgical time of 6.55 hours. All but one patient was extubated on the evening of the operating day after receiving a mean dose of 8.67 microg kg(-1) hr(-1) of fentanyl and a mean dose of 0.124 mg kg(-1) hr(-1) midazolam. The need for crystalloid infusion was 24.0 mL kg(-1) hr(-1), fresh frozen plasma (FFP)16.63 mL kg(-1) hr(-1), and red blood cells 7.98 mL kg(-1) hr(-1). There was no mortality and no anesthetic-related morbidity in our series. CONCLUSIONS: Total IV anesthesia with fentanyl, midazolam, and cisatracurium, after preoperative optimization, is a well-tolerated approach for children undergoing living-related liver transplantation and offers quick recovery. This anesthetic technique was aimed at minimizing the effects on the cardiovascular system, and also any consequences related to the possible occurrence of a reperfusion syndrome. Fluid balance was aimed at optimizing flow through the hepatic graft and preventing thrombosis of vascular anastomoses.