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1.
EBioMedicine ; 81: 104129, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1906949

ABSTRACT

BACKGROUND: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative. METHODS: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients. FINDINGS: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses. INTERPRETATION: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID. FUNDING: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/complications , Humans , Interleukin-2 , SARS-CoV-2
2.
Biochem J ; 479(8): 901-920, 2022 04 29.
Article in English | MEDLINE | ID: covidwho-1774010

ABSTRACT

Diagnostic testing continues to be an integral component of the strategy to contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) global pandemic, the causative agent of Coronavirus Disease 2019 (COVID-19). The SARS-CoV-2 genome encodes the 3C-like protease (3CLpro) which is essential for coronavirus replication. This study adapts an in vitro colorimetric gold nanoparticle (AuNP) based protease assay to specifically detect the activity of SARS-CoV-2 3CLpro as a purified recombinant protein and as a cellular protein exogenously expressed in HEK293T human cells. We also demonstrate that the specific sensitivity of the assay for SARS-CoV-2 3CLpro can be improved by use of an optimised peptide substrate and through hybrid dimerisation with inactive 3CLpro mutant monomers. These findings highlight the potential for further development of the AuNP protease assay to detect SARS-CoV-2 3CLpro activity as a novel, accessible and cost-effective diagnostic test for SARS-CoV-2 infection at the point-of-care. Importantly, this versatile assay could also be easily adapted to detect specific protease activity associated with other viruses or diseases conditions.


Subject(s)
COVID-19 , Metal Nanoparticles , Antiviral Agents , COVID-19/diagnosis , Colorimetry , Coronavirus 3C Proteases , Gold , HEK293 Cells , Humans , Peptide Hydrolases , Protease Inhibitors , SARS-CoV-2
3.
Cell Rep ; 38(7): 110393, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1719435

ABSTRACT

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies.


Subject(s)
COVID-19/immunology , Receptors, Antigen, B-Cell/immunology , Vaccination , B-Lymphocytes/immunology , COVID-19/prevention & control , Clonal Evolution , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Isotypes/genetics , Immunoglobulin Isotypes/immunology , Immunoglobulin Variable Region/genetics , Immunoglobulin Variable Region/immunology , Kinetics , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Somatic Hypermutation, Immunoglobulin/immunology , Spike Glycoprotein, Coronavirus/immunology
4.
PLoS Pathog ; 18(2): e1010265, 2022 02.
Article in English | MEDLINE | ID: covidwho-1686115

ABSTRACT

Efforts to define serological correlates of protection against COVID-19 have been hampered by the lack of a simple, scalable, standardised assay for SARS-CoV-2 infection and antibody neutralisation. Plaque assays remain the gold standard, but are impractical for high-throughput screening. In this study, we show that expression of viral proteases may be used to quantitate infected cells. Our assays exploit the cleavage of specific oligopeptide linkers, leading to the activation of cell-based optical biosensors. First, we characterise these biosensors using recombinant SARS-CoV-2 proteases. Next, we confirm their ability to detect viral protease expression during replication of authentic virus. Finally, we generate reporter cells stably expressing an optimised luciferase-based biosensor, enabling viral infection to be measured within 24 h in a 96- or 384-well plate format, including variants of concern. We have therefore developed a luminescent SARS-CoV-2 reporter cell line, and demonstrated its utility for the relative quantitation of infectious virus and titration of neutralising antibodies.


Subject(s)
Biosensing Techniques/methods , COVID-19 Testing/methods , COVID-19/virology , Luminescent Measurements/methods , Peptide Hydrolases/analysis , SARS-CoV-2/enzymology , Viral Proteins/analysis , COVID-19/diagnosis , Cell Line , Humans , Peptide Hydrolases/genetics , Peptide Hydrolases/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication
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.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1661209

ABSTRACT

Kotagiri et al. find that SARS-CoV-2 infection versus vaccination induces distinct changes in the B cell receptor repertoire, including prominent clonal expansion in IgA and IgM after infection, but IgG after vaccination. A broad anti-spike response to infection contrasts with a narrower RBD-focused one after vaccination, potentially informing vaccination strategies.

7.
Elife ; 102021 11 16.
Article in English | MEDLINE | ID: covidwho-1518777

ABSTRACT

Background: Respiratory protective equipment recommended in the UK for healthcare workers (HCWs) caring for patients with COVID-19 comprises a fluid-resistant surgical mask (FRSM), except in the context of aerosol generating procedures (AGPs). We previously demonstrated frequent pauci- and asymptomatic severe acute respiratory syndrome coronavirus 2 infection HCWs during the first wave of the COVID-19 pandemic in the UK, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Methods: Here, we use observational data and mathematical modelling to analyse infection rates amongst HCWs working on 'red' (coronavirus disease 2019, COVID-19) and 'green' (non-COVID-19) wards during the second wave of the pandemic, before and after the substitution of filtering face piece 3 (FFP3) respirators for FRSMs. Results: Whilst using FRSMs, HCWs working on red wards faced an approximately 31-fold (and at least fivefold) increased risk of direct, ward-based infection. Conversely, after changing to FFP3 respirators, this risk was significantly reduced (52-100% protection). Conclusions: FFP3 respirators may therefore provide more effective protection than FRSMs for HCWs caring for patients with COVID-19, whether or not AGPs are undertaken. Funding: Wellcome Trust, Medical Research Council, Addenbrooke's Charitable Trust, NIHR Cambridge Biomedical Research Centre, NHS Blood and Transfusion, UKRI.


Subject(s)
COVID-19/prevention & control , Health Personnel , Masks , Respiratory Protective Devices , Adult , Aerosols , Aged , COVID-19/epidemiology , Humans , Incidence , Infection Control/methods , Middle Aged , Models, Theoretical , SARS-CoV-2 , United Kingdom , Young Adult
9.
Cell Rep ; 35(13): 109292, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1281394

ABSTRACT

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.


Subject(s)
COVID-19/immunology , COVID-19/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cell Line , Chlorocebus aethiops , HEK293 Cells , Humans , Immune Evasion , Mutation , Pandemics , Phylogeny , Protein Binding , Recurrence , SARS-CoV-2/immunology , Vero Cells
10.
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
11.
Elife ; 102021 04 08.
Article in English | MEDLINE | ID: covidwho-1173059

ABSTRACT

The BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) is being utilised internationally for mass COVID-19 vaccination. Evidence of single-dose protection against symptomatic disease has encouraged some countries to opt for delayed booster doses of BNT162b2, but the effect of this strategy on rates of asymptomatic SARS-CoV-2 infection remains unknown. We previously demonstrated frequent pauci- and asymptomatic SARS-CoV-2 infection amongst healthcare workers (HCWs) during the UK's first wave of the COVID-19 pandemic, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and find a fourfold reduction in asymptomatic infection amongst HCWs ≥12 days post-vaccination. These data provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection following a single dose of BNT162b2 vaccine, suggesting that mass first-dose vaccination will reduce SARS-CoV-2 transmission, as well as the burden of COVID-19 disease.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Asymptomatic Infections/therapy , COVID-19/diagnosis , COVID-19 Vaccines/administration & dosage , Health Personnel , Humans , Immunization Schedule , Immunization, Secondary , SARS-CoV-2/isolation & purification , Vaccination
12.
Future Healthc J ; 8(1): e11-e14, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1168125

ABSTRACT

Social distancing during the coronavirus disease 2019 (COVID-19) pandemic has necessitated drastic changes in the practice of hospital medicine, including the cancellation of many educational activities. At the same time, the emergence of a new disease with a rapidly evolving knowledge base has mandated timely educational updates. To resolve this conflict in our hospital, we substituted 'traditional' grand rounds with 'virtual' grand rounds delivered over Zoom, consisting of a local situation report and operational update, followed by a specialty-specific clinical presentation on management of COVID-19. Attendance was greatly increased (mean 384 attendees) compared to traditional grand rounds (mean 44 attendees) and included a diverse audience of medical professionals. Feedback was overwhelmingly positive, with >80% of responders stating that the sessions would or might inform their clinical practice. COVID-19 has therefore provided an opportunity to modernise grand rounds, and develop a new model matching the needs of medical education beyond the pandemic.

13.
Nat Commun ; 11(1): 6385, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977267

ABSTRACT

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Immunity, Humoral/drug effects , SARS-CoV-2/drug effects , Adenosine Monophosphate/therapeutic use , Adult , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Fever/prevention & control , Humans , Immunity, Humoral/immunology , Lymphocyte Count , Male , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Treatment Outcome
14.
BMJ Open ; 10(10): e044566, 2020 10 05.
Article in English | MEDLINE | ID: covidwho-835491

ABSTRACT

OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.


Subject(s)
Biomedical Research , Coronavirus Infections , Pandemics , Patient Selection , Pneumonia, Viral , Randomized Controlled Trials as Topic , Betacoronavirus/isolation & purification , Biomedical Research/organization & administration , Biomedical Research/statistics & numerical data , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Eligibility Determination , Female , Health Services Accessibility/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Prospective Studies , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/statistics & numerical data , Registries/statistics & numerical data , SARS-CoV-2 , United Kingdom
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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