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1.
Euro Surveill ; 27(20)2022 05.
Article in English | MEDLINE | ID: covidwho-1862539

ABSTRACT

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , England/epidemiology , Hospitalization , Hospitals , Humans , SARS-CoV-2/genetics
2.
J Infect Dis ; 2022 Feb 20.
Article in English | MEDLINE | ID: covidwho-1758754

ABSTRACT

To investigate if the AY.4.2 sub-lineage of the SARS-CoV-2 Delta variant is associated with hospitalisation and mortality risks that differ from non-AY.4.2 Delta risks, we performed a retrospective cohort study of sequencing-confirmed COVID-19 cases in England based on linkage of routine healthcare datasets. Using stratified Cox regression, we estimated adjusted hazard ratios (aHR) of hospital admission (aHR=0.85, 95% CI 0.77-0.94), hospital admission or emergency care attendance (aHR=0.87, 95% CI 0.81-0.94) and COVID-19 mortality (aHR=0.85, 95% CI 0.71-1.03). The results indicate that the risks of hospitalisation and mortality is similar or lower for AY.4.2 compared to cases with other Delta sub-lineages.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329658

ABSTRACT

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

4.
N Engl J Med ; 386(16): 1532-1546, 2022 04 21.
Article in English | MEDLINE | ID: covidwho-1730372

ABSTRACT

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).


Subject(s)
COVID-19 Vaccines , COVID-19 , /therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Dihydrotachysterol , Humans , Immunization, Secondary/adverse effects , SARS-CoV-2/drug effects , SARS-CoV-2/genetics
5.
Nat Commun ; 13(1): 1012, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1709629

ABSTRACT

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.


Subject(s)
COVID-19/prevention & control , Communicable Diseases, Imported/prevention & control , Quarantine/legislation & jurisprudence , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/transmission , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/transmission , Contact Tracing , England/epidemiology , Genome, Viral/genetics , Genomics , Health Impact Assessment , Humans , SARS-CoV-2/classification , Travel/legislation & jurisprudence , Travel-Related Illness
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313569

ABSTRACT

In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -- a CD80/86 co-stimulation inhibitor -- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoV-infected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308994

ABSTRACT

Background: The emergence of VOC202012/01 in England, known as B.1.1.7 or informally as the ‘UK variant’, has coincided with rapid increases in the number of PCR-confirmed positive cases in areas where the variant has been concentrated. Methods: To assess whether infection with SARS-CoV-2 variant VOC202012/01 is associated with more severe clinical outcomes compared to wild-type infection, genomically sequenced and confirmed variant and wild-type cases were linked to routine healthcare and surveillance datasets. Two statistical analyses were conducted to compare the risk of hospital admission and death within 28 days of test between variant and wild-type cases: a case-control study and an adjusted Cox proportional hazards model. Differences in severity of disease were assessed by comparing hospital admission and mortality, including length of hospitalisation and time to death.Results: Of 63,609 genomically sequenced COVID-19 cases tested in England between October and December 2020 6,038 were variant cases. In the matched cohort analysis 2,821 variant cases were matched to 2,821 to wild-type cases. In the time to event analysis we observed a 34% increased risk in hospitalisation associated with the variant compared to wild-type cases, however, no significant difference in the risk of mortality was observed. Conclusion: We found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increase infection severity associated with this variant. Follow-up studies are needed to assess potential longer-term differences in the clinical outcomes of people infected with the VOC-202012/01 variant.

8.
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.

9.
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
10.
N Engl J Med ; 386(4): 340-350, 2022 01 27.
Article in English | MEDLINE | ID: covidwho-1621313

ABSTRACT

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.


Subject(s)
COVID-19/prevention & control , Adolescent , Adult , Age Factors , Aged , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Female , Hospitalization/statistics & numerical data , Humans , Immunization, Secondary , Immunogenicity, Vaccine , Male , Middle Aged , Patient Acuity , Risk Factors , SARS-CoV-2 , Time Factors , United Kingdom/epidemiology
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296519

ABSTRACT

Abstract Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

12.
Lancet Microbe ; 3(2): e151-e158, 2022 02.
Article in English | MEDLINE | ID: covidwho-1440435

ABSTRACT

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.


Subject(s)
COVID-19 , COVID-19/epidemiology , Disease Outbreaks , Genomics , Humans , Long-Term Care , SARS-CoV-2/genetics
13.
N Engl J Med ; 385(7): 585-594, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1319062

ABSTRACT

BACKGROUND: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. METHODS: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. RESULTS: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. CONCLUSIONS: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/virology , Case-Control Studies , Female , Humans , Male , Middle Aged , Treatment Outcome , United Kingdom/epidemiology , Vaccine Potency , Young Adult
14.
Sci Rep ; 11(1): 11462, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1253984

ABSTRACT

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.


Subject(s)
Abatacept/pharmacology , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Immunosuppressive Agents/pharmacology , SARS-CoV-2/immunology , Signal Transduction/drug effects , Abatacept/therapeutic use , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Bronchoalveolar Lavage Fluid/cytology , COVID-19/blood , COVID-19/complications , COVID-19/immunology , China , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Observational Studies as Topic , RNA-Seq , Severity of Illness Index , Signal Transduction/immunology , Single-Cell Analysis , Spain , United States , Up-Regulation/drug effects , Up-Regulation/immunology
15.
Lancet Reg Health Eur ; 3: 100038, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1192394

ABSTRACT

BACKGROUND: Care homes have been disproportionately affected by the COVID-19 pandemic. We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic. METHODS: Five care homes with no cases and two care homes reporting a single case of COVID-19 (non-outbreak homes) were investigated with nasal swabbing for SARS-CoV-2 RT-PCR and serology for SARS-CoV-2 antibodies five weeks later. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Serology results were compared with those of six care homes with recognised outbreaks. FINDINGS: Across seven non-outbreak homes, 718 (387 staff, 331 residents) individuals had a nasal swab and 651 (386 staff, 265 residents) had follow-up serology. Sixteen individuals (13 residents, 3 staff) in five care homes with no reported cases were RT-PCR positive (care home positivity rates, 0 to 7.6%) compared to 13 individuals (3.0 and 10.8% positivity) in two homes reporting a single case.Seropositivity across these seven homes varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p <0.001) across the 13 homes. WGS identified multiple introductions into some homes and silent transmission of a single lineage between staff and residents in one home. INTERPRETATION: We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak. FUNDING: PHE.

16.
Nature ; 593(7858): 266-269, 2021 05.
Article in English | MEDLINE | ID: covidwho-1152860

ABSTRACT

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.


Subject(s)
COVID-19/transmission , COVID-19/virology , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Basic Reproduction Number , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , England/epidemiology , Evolution, Molecular , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/analysis , Spike Glycoprotein, Coronavirus/genetics , Time Factors , Young Adult
17.
Age Ageing ; 50(3): 649-656, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1096485

ABSTRACT

INTRODUCTION: Previous investigations have identified high rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among residents and staff in care homes reporting an outbreak of coronavirus disease 2019 (COVID-19). We investigated care homes reporting a single suspected or confirmed case to assess whether early mass testing might reduce risk of transmission during the peak of the pandemic in London. METHODS: Between 18 and 27 April 2020, residents and staff in care homes reporting a single case of COVID-19 to Public Health England had a nasal swab to test for SARS-CoV-2 infection by reverse transcription polymerase chain reaction and subsequent whole-genome sequencing. Residents and staff in two care homes were re-tested 8 days later. RESULTS: Four care homes were investigated. SARS-CoV-2 positivity was 20% (65/333) overall, ranging between 3 and 59%. Among residents, positivity ranged between 3 and 76% compared with 3 and 40% in staff. Half of the SARS-CoV-2-positive residents (23/46, 50%) and 63% of staff (12/19) reported symptoms within 14 days before or after testing. Repeat testing 8 days later in two care homes with the highest infection rates identified only two new cases. Genomic analysis demonstrated a small number of introduction of the virus into care homes, and distinct clusters within three of the care homes. CONCLUSIONS: We found extensive but variable rates of SARS-CoV-2 infection among residents and staff in care homes reporting a single case of COVID-19. Although routine whole-home testing has now been adopted into practice, care homes must remain vigilant and should be encouraged to report a single suspected case, which should trigger appropriate outbreak control measures.


Subject(s)
COVID-19/diagnosis , Mass Screening/statistics & numerical data , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/transmission , COVID-19 Nucleic Acid Testing , COVID-19 Testing , England , Female , Humans , Infection Control , London/epidemiology , Long-Term Care , Male , Pandemics , Policy , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Whole Genome Sequencing
20.
Lancet Reg Health Eur ; 2: 100015, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-988715

ABSTRACT

BACKGROUND: Military personnel in enclosed societies are at increased risk of respiratory infections. We investigated an outbreak of Coronavirus Disease 2019 in a London Army barracks early in the pandemic. METHODS: Army personnel, their families and civilians had nasal and throat swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcriptase -polymerase chain reaction (RT-PCR), virus isolation and whole genome sequencing, along with blood samples for SARS-CoV-2 antibodies. All tests were repeated 36 days later. FINDINGS: During the first visit, 304 (254 Army personnel, 10 family members, 36 civilians, 4 not stated) participated and 24/304 (8%) were SARS-CoV-2 RT-PCR positive. Infectious virus was isolated from 7/24 (29%). Of the 285 who provided a blood sample, 7% (19/285) were antibody positive and 63% (12/19) had neutralising antibodies. Twenty-two (22/34, 64%) individuals with laboratory-confirmed infection were asymptomatic. Nine SARS-CoV-2 RT-PCR positive participants were also antibody positive but those who had neutralising antibodies did not have infectious virus. At the second visit, no new infections were detected, and 13% (25/193) were seropositive, including 52% (13/25) with neutralising antibodies. Risk factors for SARS-CoV-2 antibody positivity included contact with a confirmed case (RR 25.2; 95% CI 14-45), being female (RR 2.5; 95% CI 1.0-6.0) and two-person shared bathroom (RR 2.6; 95% CI 1.1-6.4). INTERPRETATION: We identified high rates of asymptomatic SARS-CoV-2 infection. Public Health control measures can mitigate spread but virus re-introduction from asymptomatic individuals remains a risk. Most seropositive individuals had neutralising antibodies and infectious virus was not recovered from anyone with neutralising antibodies. FUNDING: PHE.

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