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1.
Lancet Infect Dis ; 2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1598838

ABSTRACT

BACKGROUND: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. METHODS: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. FINDINGS: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. INTERPRETATION: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. FUNDING: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

2.
Preprint in English | Other preprints | ID: ppcovidwho-295014

ABSTRACT

Introduction SARS-CoV-2 serological studies have so far focused mainly on adults. Public Health England initiated prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England after the first national lockdown, which allowed comparison of child and adult responses to SARS-CoV-2 infection over time. Methods Staff and students had venepuncture for SARS-CoV-2 antibodies in school during June, July and December 2020. Blood samples were tested for nucleocapsid (Abbott) and receptor binding domain (RBD) antibodies (in-house assay), and student samples were additionally assessed for live virus neutralising activity. Results In June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95% CI: 9.4-13.9) and 11.3% (95% CI: 9.2-13.6;p=0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95% CI: 13.7-17.6) and 15.3% (95% CI: 13.4-17.3;p=0.83) of staff. Live virus neutralising activity was detected in 79.8% (n=71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (r s =0.7527;p<0.0001) than nucleocapsid antibodies (r s =0.3698;p<0.0001). A median of 24.4 weeks later, 58.2% (107/184) participants had nucleocapsid antibody seroreversion, compared to 20.9% (33/158) for RBD (p<0.001). Similar seroreversion rates were observed between staff and students for nucleocapsid (p=0.26) and RBD-antibodies (p=0.43). Nucleocapsid and RBD antibody quantitative results were significantly lower in staff compared to students (p=0.028 and <0.0001 respectively) at baseline, but not at 24 weeks (p=0.16 and p=0.37, respectively). Conclusion RBD antibodies correlated more strongly with live virus neutralising activity. Most seropositive students and staff retained RBD antibodies for >6 months after SARS-CoV-2 infection.

3.
Preprint in English | Other preprints | ID: ppcovidwho-294092

ABSTRACT

Background Most individuals with COVID-19 will recover without sequelae, but some will develop long- term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. Methods Public Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. Results All 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. Conclusions Most persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with previous COVID-19 infection, the sensory cluster had the highest specificity and strength of association. Key points Compared to controls, we identified three clusters of symptoms affecting the sensory, neurological and cardiorespiratory systems that were more prevalent among cases. Notably, gastrointestinal and dermatological symptoms and symptoms related to mental health were as prevalent among cases as controls.

4.
EClinicalMedicine ; 41: 101150, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1446584

ABSTRACT

Background: Prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England was initiated after the first national lockdown, allowing comparison of child and adult antibody responses over time. Methods: Prospective active serological surveillance in 46 primary schools in England tested for SARS-CoV-2 antibodies during June, July and December 2020. Samples were tested for nucleocapsid (N) and receptor binding domain (RBD) antibodies, to estimate antibody persistence at least 6 months after infection, and for the correlation of N, RBD and live virus neutralising activity. Findings: In June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95%CI: 9.4-13.9) and 11.3% (95%CI: 9.2-13.6; p = 0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95%CI: 13.7-17.6) and 15.3% (95%CI: 13.4-17.3; p = 0.83) of staff. Live virus neutralising activity was detected in 79.8% (n = 71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (rs=0.7527; p<0.0001) than nucleocapsid antibodies (rs=0.3698; p<0.0001). A median of 24.4 weeks later, 58.2% (107/184) participants had nucleocapsid antibody seroreversion, compared to 20.9% (33/158) for RBD (p<0.001). Similar seroreversion rates were observed between staff and students for nucleocapsid (p = 0.26) and RBD-antibodies (p = 0.43). Nucleocapsid and RBD antibody quantitative results were significantly lower in staff compared to students (p = 0.028 and <0.0001 respectively) at baseline, but not at 24 weeks (p = 0.16 and p = 0.37, respectively). Interpretation: The immune response in children following SARS-CoV-2 infection was robust and sustained (>6 months) but further work is required to understand the extent to which this protects against reinfection.

5.
J Infect Dis ; 224(3): 389-394, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338710

ABSTRACT

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Respiratory System/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Postmortem Changes , Sensitivity and Specificity , Young Adult
7.
BMJ ; 373: n1412, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1270886

ABSTRACT

OBJECTIVE: To evaluate the relation between diagnosis of covid-19 with SARS-CoV-2 variant B.1.1.7 (also known as variant of concern 202012/01) and the risk of hospital admission compared with diagnosis with wild-type SARS-CoV-2 variants. DESIGN: Retrospective cohort analysis. SETTING: Community based SARS-CoV-2 testing in England, individually linked with hospital admission data. PARTICIPANTS: 839 278 patients with laboratory confirmed covid-19, of whom 36 233 had been admitted to hospital within 14 days, tested between 23 November 2020 and 31 January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF), a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. MAIN OUTCOME MEASURES: Hospital admission between one and 14 days after the first positive SARS-CoV-2 test. RESULTS: 27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with covid-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P<0.001), with hazard ratios of 0.93-1.21 in patients younger than 20 years with versus without SGTF variants, 1.29 in those aged 20-29, and 1.45-1.65 in those aged ≥30 years. The adjusted absolute risk of hospital admission within 14 days was 4.7% (95% confidence interval 4.6% to 4.7%) for patients with SGTF variants and 3.5% (3.4% to 3.5%) for those with non-SGTF variants. CONCLUSIONS: The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.


Subject(s)
COVID-19/virology , Hospitalization/statistics & numerical data , SARS-CoV-2/pathogenicity , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , COVID-19 Testing , Child , England/epidemiology , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Young Adult
8.
J Infect Dis ; 224(3): 389-394, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1231036

ABSTRACT

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Respiratory System/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Postmortem Changes , Sensitivity and Specificity , Young Adult
9.
Influenza Other Respir Viruses ; 15(5): 599-607, 2021 09.
Article in English | MEDLINE | ID: covidwho-1214794

ABSTRACT

BACKGROUND: During 2009-2010, pandemic influenza A (H1N1) pdm09 virus (pH1N1) infections in England occurred in two epidemic waves. Reasons for a reported increase in case-severity during the second wave are unclear. METHODS: We analysed hospital-based surveillance for patients with pH1N1 infections in England during 2009-2010 and linked national data sets to estimate ethnicity, socio-economic status and death within 28 days of admission. We used multivariable logistic regression to assess whether changes in demographic, clinical and management characteristics of patients could explain an increase in ICU admission or death, and accounted for missing values using multiple imputation. RESULTS: During the first wave, 54/960 (6%) hospitalised patients required intensive care and 21/960 (2%) died; during the second wave 143/1420 (10%) required intensive care and 55/1420 (4%) died. In a multivariable model, during the second wave patients were less likely to be from an ethnic minority (OR 0.33, 95% CI 0.26-0.42), have an elevated deprivation score (OR 0.75, 95% CI 0.68-0.83), have known comorbidity (OR 0.78, 95% CI 0.63-0.97) or receive antiviral therapy ≤2 days before onset (OR 0.72, 95% CI 0.56-0.92). Increased case-severity during the second wave was not explained by changes in demographic, clinical or management characteristics. CONCLUSIONS: Monitoring changes in patient characteristics could help target interventions during multiple waves of COVID-19 or a future influenza pandemic. To understand and respond to changes in case-severity, surveillance is needed that includes additional factors such as admission thresholds and seasonal coinfections.


Subject(s)
Epidemics , Influenza A Virus, H1N1 Subtype , Influenza, Human , Adolescent , Adult , England/epidemiology , Epidemics/history , Female , History, 21st Century , Hospitalization , Humans , Influenza, Human/epidemiology , Male , Middle Aged , Minority Groups , Young Adult
10.
J Infect ; 82(5): 162-169, 2021 05.
Article in English | MEDLINE | ID: covidwho-1142042

ABSTRACT

BACKGROUND: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England. METHODS: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression. FINDINGS: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S). INTERPRETATION: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , Antibody Formation , England , Health Personnel , Humans , Prospective Studies , Public Health
11.
Emerg Infect Dis ; 27(4): 1155-1158, 2021 04.
Article in English | MEDLINE | ID: covidwho-1140631

ABSTRACT

Prospective serosurveillance of severe acute respiratory syndrome coronavirus 2 in 1,069 healthcare workers in London, UK, demonstrated that nucleocapsid antibody titers were stable and sustained for <12 weeks in 312 seropositive participants. This finding was consistent across demographic and clinical variables and contrasts with reports of short-term antibody waning.


Subject(s)
Antibodies, Viral/blood , Antibody Formation/immunology , COVID-19 Serological Testing , COVID-19 , Coronavirus Nucleocapsid Proteins/immunology , Health Personnel/statistics & numerical data , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Female , Humans , London/epidemiology , Male , Phosphoproteins/immunology , SARS-CoV-2/isolation & purification , Seroconversion , Seroepidemiologic Studies
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