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1.
Clin Infect Dis ; 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-2017776

ABSTRACT

Airborne SARS-CoV-2 was detected in a COVID-19 ward before activation of portable HEPA-air filtration, but not during the week of filter operation; SARS-CoV-2 was again detected when the filter was off. Airborne SARS-CoV-2 was infrequently detected in a COVID-19 ICU. Filtration significantly reduced other microbial bioaerosols in both settings.

2.
Journal of Infection ; 2022.
Article in English | ScienceDirect | ID: covidwho-2007856

ABSTRACT

Objectives To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). Methods We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. Results 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71];p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42];p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25];p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 – 2·07;p<0·001) compared to white staff;this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia;31% of staff testing positive reported no prior symptoms. Conclusions Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

3.
Sci Transl Med ; 14(638): eabn4342, 2022 03 30.
Article in English | MEDLINE | ID: covidwho-1769820

ABSTRACT

New technologies and unprecedented public investment have transformed vaccine development and allowed fast delivery of safe and efficacious COVID-19 vaccines, mitigating the impact of the pandemic on health and the economy. A quantum change in public investment for vaccine development and widespread vaccine distribution are necessary to achieve global pandemic preparedness.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Influenza, Human/epidemiology , Pandemics/prevention & control
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-304909

ABSTRACT

Understanding the drivers for spread of SARS-CoV-2 in higher education settings is important to limit transmission between students, and onward spread into at-risk populations. In this study, we prospectively sequenced 482 SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge from 5 October to 6 December 2020. We performed a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. After a limited number of viral introductions into the university, the majority of student cases were linked to a single genetic cluster, likely dispersed across the university following social gatherings at a venue outside the university. We identified considerable onward transmission associated with student accommodation and courses;this was effectively contained using local infection control measures and dramatically reduced following a national lockdown. We observed that transmission clusters were largely segregated within the university or within the community. This study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.

5.
Nat Commun ; 13(1): 751, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1684022

ABSTRACT

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Universities , COVID-19/prevention & control , COVID-19/virology , Contact Tracing , Genome, Viral/genetics , Genomics , Humans , Phylogeny , RNA, Viral/genetics , Risk Factors , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Students , United Kingdom/epidemiology , Universities/statistics & numerical data
6.
Ann N Y Acad Sci ; 1511(1): 59-86, 2022 05.
Article in English | MEDLINE | ID: covidwho-1625044

ABSTRACT

The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low-and-middle-income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28-30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium "Innovative Vaccine Approaches" to discuss advances in vaccine research and development.


Subject(s)
COVID-19 , Influenza Vaccines , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Global Health , Humans , Pandemics/prevention & control , Vaccines/therapeutic use
7.
Clin Infect Dis ; 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1493776

ABSTRACT

Airborne SARS-CoV-2 was detected in a COVID-19 ward before activation of portable HEPA-air filtration, but not during the week of filter operation; SARS-CoV-2 was again detected when the filter was off. Airborne SARS-CoV-2 was infrequently detected in a COVID-19 ICU. Filtration significantly reduced other microbial bioaerosols in both settings.

8.
Immunity ; 54(6): 1257-1275.e8, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1230571

ABSTRACT

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions/immunology , Lymphocyte Activation/immunology , SARS-CoV-2/immunology , Biomarkers , CD8-Positive T-Lymphocytes/metabolism , COVID-19/diagnosis , COVID-19/genetics , Cytokines/metabolism , Disease Susceptibility , Gene Expression Profiling , Humans , Inflammation Mediators/metabolism , Longitudinal Studies , Lymphocyte Activation/genetics , Oxidative Phosphorylation , Phenotype , Prognosis , Reactive Oxygen Species/metabolism , Severity of Illness Index , Transcriptome
10.
Elife ; 102021 03 02.
Article in English | MEDLINE | ID: covidwho-1112865

ABSTRACT

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Nursing Homes , SARS-CoV-2/genetics , Aged, 80 and over , COVID-19/virology , Disease Outbreaks , England/epidemiology , Female , Humans , Infectious Disease Transmission, Patient-to-Professional , Infectious Disease Transmission, Professional-to-Patient , Male , Polymorphism, Single Nucleotide , Sequence Analysis , Time Factors
11.
Cell Rep Med ; 1(5): 100062, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-1026726

ABSTRACT

There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.6 (IQR 2.3-4.8) versus 26.4 h (IQR 21.4-31.4, p < 0.001), with 32 (21.5%) positive and 117 (78.5%) negative. Cohen's κ correlation between tests is 0.96 (95% CI 0.91-1.00). When comparing nearly 1,000 tests pre- and post-implementation, the median time to definitive bed placement from admission is 23.4 (8.6-41.9) versus 17.1 h (9.0-28.8), p = 0.02. Mean length of stay on COVID-19 "holding" wards is 58.5 versus 29.9 h (p < 0.001). POC testing increases isolation room availability, avoids bed closures, allows discharge to care homes, and expedites access to hospital procedures. POC testing could mitigate the impact of COVID-19 on hospital systems.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Infection Control/methods , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Adult , Aged , COVID-19 Nucleic Acid Testing/standards , Cross Infection/prevention & control , Female , Hospitalization , Humans , Male , Middle Aged , Point-of-Care Testing/standards , SARS-CoV-2/genetics
12.
Wellcome Open Res ; 5: 110, 2020.
Article in English | MEDLINE | ID: covidwho-1024789

ABSTRACT

The COVID-19 pandemic is expanding at an unprecedented rate. As a result, diagnostic services are stretched to their limit, and there is a clear need for the provision of additional diagnostic capacity. Academic laboratories, many of which are closed due to governmental lockdowns, may be in a position to support local screening capacity by adapting their current laboratory practices. Here, we describe the process of developing a SARS-Cov2 diagnostic workflow in a conventional academic Containment Level 2 laboratory. Our outline includes simple SARS-Cov2 deactivation upon contact, the method for a quantitative real-time reverse transcriptase PCR detecting SARS-Cov2, a description of process establishment and validation, and some considerations for establishing a similar workflow elsewhere. This was achieved under challenging circumstances through the collaborative efforts of scientists, clinical staff, and diagnostic staff to mitigate to the ongoing crisis. Within 14 days, we created a validated COVID-19 diagnostics service for healthcare workers in our local hospital. The described methods are not exhaustive, but we hope may offer support to other academic groups aiming to set up something comparable in a short time frame.

13.
Crit Care ; 25(1): 25, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1021404

ABSTRACT

BACKGROUND: Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). OBJECTIVES: To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients. METHODS: In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020. RESULTS: COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14-3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19. CONCLUSION: COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Pneumonia, Ventilator-Associated/epidemiology , Aged , COVID-19/diagnosis , Female , Humans , Intensive Care Units/trends , Male , Middle Aged , Pneumonia, Ventilator-Associated/diagnosis , Retrospective Studies
15.
Lancet Infect Dis ; 20(11): 1263-1272, 2020 11.
Article in English | MEDLINE | ID: covidwho-643826

ABSTRACT

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Cross Infection/epidemiology , Cross Infection/prevention & control , Infection Control/methods , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Coronavirus Infections/virology , Cross Infection/virology , England/epidemiology , Female , Genome, Viral/genetics , Hospitals, University , Humans , Infant , Infant, Newborn , Male , Middle Aged , Patient Safety , Phylogeny , Pneumonia, Viral/virology , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Prospective Studies , SARS-CoV-2 , Whole Genome Sequencing/methods , Young Adult
16.
Elife ; 92020 06 19.
Article in English | MEDLINE | ID: covidwho-607959

ABSTRACT

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK 'lockdown'. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent 'hubs' of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.


Subject(s)
Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/transmission , Health Personnel , Mass Screening/statistics & numerical data , Occupational Diseases/prevention & control , Pandemics , Pneumonia, Viral/transmission , Adult , Asymptomatic Diseases , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Community-Acquired Infections/transmission , Contact Tracing , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Disease Transmission, Infectious/prevention & control , England/epidemiology , Family Characteristics , Female , Hospital Units , Hospitals, Teaching/organization & administration , Hospitals, Teaching/statistics & numerical data , Hospitals, University/organization & administration , Hospitals, University/statistics & numerical data , Humans , Infection Control , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Male , Mass Screening/organization & administration , Middle Aged , Nasopharynx/virology , Occupational Diseases/epidemiology , Pandemics/prevention & control , Patient Admission/statistics & numerical data , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Prevalence , Program Evaluation , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Symptom Assessment
17.
Elife ; 92020 05 11.
Article in English | MEDLINE | ID: covidwho-236326

ABSTRACT

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.


Patients admitted to NHS hospitals are now routinely screened for SARS-CoV-2 (the virus that causes COVID-19), and isolated from other patients if necessary. Yet healthcare workers, including frontline patient-facing staff such as doctors, nurses and physiotherapists, are only tested and excluded from work if they develop symptoms of the illness. However, there is emerging evidence that many people infected with SARS-CoV-2 never develop significant symptoms: these people will therefore be missed by 'symptomatic-only' testing. There is also important data showing that around half of all transmissions of SARS-CoV-2 happen before the infected individual even develops symptoms. This means that much broader testing programs are required to spot people when they are most infectious. Rivett, Sridhar, Sparkes, Routledge et al. set out to determine what proportion of healthcare workers was infected with SARS-CoV-2 while also feeling generally healthy at the time of testing. Over 1,000 staff members at a large UK hospital who felt they were well enough to work, and did not fit the government criteria for COVID-19 infection, were tested. Amongst these, 3% were positive for SARS-CoV-2. On closer questioning, around one in five reported no symptoms, two in five very mild symptoms that they had dismissed as inconsequential, and a further two in five reported COVID-19 symptoms that had stopped more than a week previously. In parallel, healthcare workers with symptoms of COVID-19 (and their household contacts) who were self-isolating were also tested, in order to allow those without the virus to quickly return to work and bolster a stretched workforce. Finally, the rates of infection were examined to probe how the virus could have spread through the hospital and among staff ­ and in particular, to understand whether rates of infection were greater among staff working in areas devoted to COVID-19 patients. Despite wearing appropriate personal protective equipment, healthcare workers in these areas were almost three times more likely to test positive than those working in areas without COVID-19 patients. However, it is not clear whether this genuinely reflects greater rates of patients passing the infection to staff. Staff may give the virus to each other, or even acquire it at home. Overall, this work implies that hospitals need to be vigilant and introduce broad screening programmes across their workforces. It will be vital to establish such approaches before 'lockdown' is fully lifted, so healthcare institutions are prepared for any second peak of infections.


Subject(s)
Asymptomatic Infections , Clinical Laboratory Techniques , Health Personnel , Betacoronavirus/physiology , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Female , Humans , Infection Control , Male , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , United Kingdom/epidemiology
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