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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322658

ABSTRACT

Background: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. Little is known about the impact their increased infectivity has on transmission within hospitals.Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences.Findings: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages.Interpretation: Notwithstanding evidence from community studies that the Alpha variant is more transmissible, we find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.Funding Information: COG-UK HOCI funded by COG-UK consortium. The COG-UK consortium is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute.Declaration of Interests: None to declare. Ethics Approval Statement: Ethical approval for the HOCI study was provided by REC 20/EE/0118.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322107

ABSTRACT

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for acute SARS-CoV-2 infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim in this retrospective study was to determine the impact of serial SARS-CoV-2 qPCR Ct-values, among critically ill COVID-19 patients both prior and during intensive care unit (ICU) stay, on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI). There was a continuous increment in Ct-values over the ICU stay from 1 st -week through to 3 rd -week. Although not significant, lower ICU 1 st -week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1 st -week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20.To our knowledge this is the first report showing the impact of Ct-values and outcomes, especially AKI, among patients at different time point’s prior to and during ICU stay.

3.
[Unspecified Source]; 2020.
Preprint in English | [Unspecified Source] | ID: ppcovidwho-292783

ABSTRACT

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (T(FH)) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells. Importantly, the CD4-CTLs were highly enriched for the expression of transcripts encoding chemokines that are involved in the recruitment of myeloid cells and dendritic cells to the sites of viral infection. Polyfunctional T helper (T(H))1 cells and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2 reactive CD4+ T cells in distinct disease severities. Funding: This work was funded by NIH grants U19AI142742 (P.V., A.S., C.H.O), U19AI118626 (P.V., A.S., G.S.), R01HL114093 (P.V., F.A., G.S.,), R35-GM128938 (F.A), S10RR027366 (BD FACSAria-II), S10OD025052 (Illumina Novaseq6000), the William K. Bowes Jr Foundation (P.V.), and Whittaker foundation (P.V., C.H.O.). Supported by the Wessex Clinical Research Network and National Institute of Health Research UK. Conflict of Interest: The authors declare no competing financial interests. Ethical Approval: Ethical approval for this study from the Berkshire Research Ethics Committee 20/SC/0155 and the Ethics Committee of La Jolla Institute for Immunology (LJI) was in place. Written consent was obtained from all subjects.

4.
Non-conventional in English | MEDLINE, Grey literature | ID: grc-750510

ABSTRACT

The molecular properties of CD8 + T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 + T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 + T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the non-exhausted subsets from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8 + T cell memory responses in patients with severe COVID-19 illness. CD8 + T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8 + T cells responding to SARS-CoV-2.

5.
J Infect ; 83(6): 693-700, 2021 12.
Article in English | MEDLINE | ID: covidwho-1446866

ABSTRACT

OBJECTIVES: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. METHODS: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. RESULTS: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. CONCLUSIONS: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Hospitals , Humans , SARS-CoV-2 , United Kingdom/epidemiology
6.
Infez Med ; 29(3): 386-392, 2021.
Article in English | MEDLINE | ID: covidwho-1444692

ABSTRACT

Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim, in this retrospective study, was to determine the impact of serial SARS-CoV-2 qPCR Ct-values on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) with COVID-19. Ct values were evaluated during the time points from pre-ICU admission to week 1, week 2 and week 3 during ICU stay; impact on mortality, need for MV and AKI was determined. There was a continuous increment in Ct-values over the ICU stay from 1st week through to 3rd week. Although not significant, lower ICU 1st week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20. This report shows that the impact of Ct-values and outcomes, especially AKI, among patients at different time points prior to and during ICU stay, larger studies are required to confirm out findings.

7.
BMJ Open Respir Res ; 8(1)2021 09.
Article in English | MEDLINE | ID: covidwho-1430193

ABSTRACT

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/virology , COVID-19 Testing , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Severity of Illness Index , United Kingdom , Young Adult
8.
J Infect Prev ; 23(1): 7-10, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1390467

ABSTRACT

The importance of SARS-CoV-2 transmission via contact routes and its stability on surfaces is becoming increasingly recognised. There is ongoing concern that patients can become infected through person-to-person spread and environment-to-person spread. This study assessed whether SARS-CoV-2 viral RNA can be detected in the environment either on staff members' personal protective equipment (PPE), on high-touch surfaces or around the bedspace of COVID-19-positive patients in a range of different ward settings to evaluate if there was any contamination of these. Results showed all PPE and high-touch surface swabs were negative. All swabs taken in the negative-pressure room where aerosol-generating procedures (AGPs) were being undertaken detected viral RNA (5/5 positive), whereas there was minimal contamination in the intensive therapy unit (1/5 positive) and none detected in the cohort bay. These findings would be consistent with the understanding that areas where AGPs are regularly performed are at higher risk of environmental contamination.

10.
Arch Dis Child Educ Pract Ed ; 107(1): 39-44, 2022 02.
Article in English | MEDLINE | ID: covidwho-1143018
11.
Sci Immunol ; 6(55)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1042797

ABSTRACT

The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Female , Glycolysis/immunology , Humans , Immunologic Memory/immunology , Male , Middle Aged , NF-kappa B/immunology , Signal Transduction/immunology , Single-Cell Analysis/methods , Young Adult
12.
J Infect Prev ; 22(4): 156-161, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-977667

ABSTRACT

BACKGROUND: We report an outbreak of SARS coronavirus-2 (SARS-CoV-2) infection among healthcare workers (HCW) in an NHS elective healthcare facility. METHODOLOGY: A narrative chronological account of events after declaring an outbreak of SARS-CoV-2 among HCWs. As part of the investigations, HCWs were offered testing during the outbreak. These were: (1) screening by real-time reverse transcriptase polymerase chain reaction (RT- PCR) to detect a current infection; and (2) serum samples to determine seroprevalence. RESULTS: Over 180 HCWs were tested by real-time RT-PCR for SARS-CoV-2 infection. The rate of infection was 15.2% (23.7% for clinical or directly patient-facing HCWs vs. 4.8% in non-clinical non-patient-facing HCWs). Of the infected HCWs, 57% were asymptomatic. Seroprevalence (SARS-CoV-2 IgG) among HCWs was 13%. It was challenging to establish an exact source for the outbreak. The importance of education, training, social distancing and infection prevention practices were emphasised. Additionally, avoidance of unnecessary transfer of patients and minimising cross-site working for staff and early escalation were highlighted. Establishing mass and regular screening for HCWs are also crucial to enabling the best care for patients while maintaining the wellbeing of staff. CONCLUSION: To our knowledge, this is the first UK outbreak report among HCWs and we hope to have highlighted some key issues and learnings that can be considered by other NHS staff and HCWs globally when dealing with such a task in future.

13.
SSRN ; : 3641939, 2020 Jul 07.
Article in English | MEDLINE | ID: covidwho-892408

ABSTRACT

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells. Importantly, the CD4-CTLs were highly enriched for the expression of transcripts encoding chemokines that are involved in the recruitment of myeloid cells and dendritic cells to the sites of viral infection. Polyfunctional T helper (TH)1 cells and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2 reactive CD4+ T cells in distinct disease severities. Funding: This work was funded by NIH grants U19AI142742 (P.V., A.S., C.H.O), U19AI118626 (P.V., A.S., G.S.), R01HL114093 (P.V., F.A., G.S.,), R35-GM128938 (F.A), S10RR027366 (BD FACSAria-II), S10OD025052 (Illumina Novaseq6000), the William K. Bowes Jr Foundation (P.V.), and Whittaker foundation (P.V., C.H.O.). Supported by the Wessex Clinical Research Network and National Institute of Health Research UK. Conflict of Interest: The authors declare no competing financial interests. Ethical Approval: Ethical approval for this study from the Berkshire Research Ethics Committee 20/SC/0155 and the Ethics Committee of La Jolla Institute for Immunology (LJI) was in place. Written consent was obtained from all subjects.

14.
Cell ; 183(5): 1340-1353.e16, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-888424

ABSTRACT

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (TH) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional TH1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.


Subject(s)
COVID-19/immunology , SARS-CoV-2/genetics , T Follicular Helper Cells/immunology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Regulatory/immunology , Transcriptome , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , CD4 Lymphocyte Count , COVID-19/epidemiology , COVID-19/virology , Cohort Studies , England/epidemiology , Female , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Single-Cell Analysis/methods , Spike Glycoprotein, Coronavirus/immunology
15.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1551

ABSTRACT

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell

16.
bioRxiv ; 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-664327

ABSTRACT

The molecular properties of CD8 + T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 + T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 + T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the non-exhausted subsets from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8 + T cell memory responses in patients with severe COVID-19 illness. CD8 + T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8 + T cells responding to SARS-CoV-2.

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