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1.
Heliyon ; : e12744, 2022.
Article in English | ScienceDirect | ID: covidwho-2165334

ABSTRACT

SARS-CoV-2 depends on host cell components for infection and replication. Identification of virus-host dependencies offers an effective way to elucidate mechanisms involved in viral infection and replication. If druggable, host factor dependencies may present an attractive strategy for anti-viral therapy. In this study, we performed genome wide CRISPR knockout screens in Vero E6 cells and four human cell lines including Calu-3, UM-UC-4, HEK-293 and HuH-7 to identify genetic regulators of SARS-CoV-2 infection. Our findings identified only ACE2, the cognate SARS-CoV-2 entry receptor, as a common host dependency factor across all cell lines, while other host genes identified were largely cell line specific, including known factors TMPRSS2 and CTSL. Several of the discovered host-dependency factors converged on pathways involved in cell signalling, immune-related pathways, and chromatin modification. Notably, the chromatin modifier gene KMT2C in Calu-3 cells had the strongest impact in preventing SARS-CoV-2 infection when perturbed.

2.
PLoS One ; 17(11): e0264240, 2022.
Article in English | MEDLINE | ID: covidwho-2109283

ABSTRACT

OBJECTIVES: To examine how the COVID-19 pandemic affected the demographic and clinical characteristics, in-hospital care, and outcomes of long-term care residents admitted to general medicine wards for non-COVID-19 reasons. METHODS: We conducted a retrospective cohort study of long-term care residents admitted to general medicine wards, for reasons other than COVID-19, in four hospitals in Toronto, Ontario between January 1, 2018 and December 31, 2020. We used an autoregressive linear model to estimate the change in monthly admission volumes during the pandemic period (March-December 2020) compared to the previous two years, adjusting for any secular trend. We summarized and compared differences in the demographics, comorbidities, interventions, diagnoses, imaging, psychoactive medications, and outcomes of residents before and during the pandemic. RESULTS: Our study included 2,654 long-term care residents who were hospitalized for non-COVID-19 reasons between January 2018 and December 2020. The crude rate of hospitalizations was 79.3 per month between March-December of 2018-2019 and 56.5 per month between March-December of 2020. The was an adjusted absolute difference of 27.0 (95% CI: 10.0, 43.9) fewer hospital admissions during the pandemic period, corresponding to a relative drop of 34%. Residents admitted during the pandemic period had similar demographics and clinical characteristics but were more likely to be admitted for delirium (pandemic: 7% pre-pandemic: 5%, p = 0.01) and were less likely to be admitted for pneumonia (pandemic: 3% pre-pandemic: 6%, p = 0.004). Residents admitted during the pandemic were more likely to be prescribed antipsychotics (pandemic: 37%, pre-pandemic: 29%, p <0.001) and more likely to die in-hospital (pandemic:14% pre-pandemic: 10%, p = 0.04). CONCLUSIONS AND IMPLICATIONS: Better integration between long-term care and hospitals systems, including programs to deliver urgent medical care services within long-term care homes, is needed to ensure that long-term care residents maintain equitable access to acute care during current and future public health emergencies.


Subject(s)
COVID-19 , Long-Term Care , Humans , COVID-19/epidemiology , Pandemics , Retrospective Studies , Ontario/epidemiology , Hospitalization
3.
PLoS One ; 17(10): e0276507, 2022.
Article in English | MEDLINE | ID: covidwho-2079771

ABSTRACT

OBJECTIVES: We aimed to estimate associations between COVID-19 incidence and mortality with neighbourhood-level immigration, race, housing, and socio-economic characteristics. METHODS: We conducted a population-based study of 28,808 COVID-19 cases in the provincial reportable infectious disease surveillance systems (Public Health Case and Contact Management System) which includes all known COVID-19 infections and deaths from Ontario, Canada reported between January 23, 2020 and July 28, 2020. Residents of congregate settings, Indigenous communities living on reserves or small neighbourhoods with populations <1,000 were excluded. Comparing neighbourhoods in the 90th to the 10th percentiles of socio-demographic characteristics, we estimated the associations between 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics and COVID-19 incidence and mortality using Poisson generalized linear mixed models. RESULTS: Neighbourhoods with the highest proportion of immigrants (relative risk (RR): 4.0, 95%CI:3.5-4.5) and visible minority residents (RR: 3.3, 95%CI:2.9-3.7) showed the strongest association with COVID-19 incidence in adjusted models. Among individual race groups, COVID-19 incidence was highest among neighbourhoods with the high proportions of Black (RR: 2.4, 95%CI:2.2-2.6), South Asian (RR: 1.9, 95%CI:1.8-2.1), Latin American (RR: 1.8, 95%CI:1.6-2.0) and Middle Eastern (RR: 1.2, 95%CI:1.1-1.3) residents. Neighbourhoods with the highest average household size (RR: 1.9, 95%CI:1.7-2.1), proportion of multigenerational families (RR: 1.8, 95%CI:1.7-2.0) and unsuitably crowded housing (RR: 2.1, 95%CI:2.0-2.3) were associated with COVID-19 incidence. Neighbourhoods with the highest proportion of residents with less than high school education (RR: 1.6, 95%CI:1.4-1.8), low income (RR: 1.4, 95%CI:1.2-1.5) and unaffordable housing (RR: 1.6, 95%CI:1.4-1.8) were associated with COVID-19 incidence. Similar inequities were observed across neighbourhood-level sociodemographic characteristics and COVID-19 mortality. CONCLUSIONS: Neighbourhood-level inequities in COVID-19 incidence and mortality were observed in Ontario, with excess burden experienced in neighbourhoods with a higher proportion of immigrants, racialized populations, large households and low socio-economic status.


Subject(s)
COVID-19 , Humans , Incidence , Ontario/epidemiology , COVID-19/epidemiology , Residence Characteristics , Family Characteristics , Socioeconomic Factors
4.
PLoS One ; 17(2): e0262515, 2022.
Article in English | MEDLINE | ID: covidwho-1688746

ABSTRACT

BACKGROUND: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. METHODS: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. RESULTS: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. INTERPRETATION: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Adolescent , Adult , Antibodies, Viral/analysis , COVID-19/virology , Child , Contact Tracing , England/epidemiology , Female , Humans , Incidence , Male , Nasopharynx/virology , Prospective Studies , RNA, Viral/analysis , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Schools/statistics & numerical data , Students/statistics & numerical data
6.
Open Forum Infect Dis ; 9(9): ofac449, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2037503

ABSTRACT

Background: Waning protection from 2 doses of coronavirus disease 2019 (COVID-19) vaccines led to third dose availability in multiple countries even before the emergence of the Omicron variant. Methods: We used the test-negative study design to estimate vaccine effectiveness (VE) against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, any symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between January 11, and November 21, 2021, for subgroups based on patient and vaccine characteristics. Results: We included 261 360 test-positive cases (of any SARS-CoV-2 lineage) and 2 783 699 individuals as test-negative controls. VE of 2 mRNA vaccine doses decreased from 90% (95% CI, 90%-90%) 7-59 days after the second dose to 75% (95% CI, 72%-78%) after ≥240 days against infection, decreased from 94% (95% CI, 84%-95%) to 87% (95% CI, 85%-89%) against symptomatic infection, and remained stable (98% [95% CI, 97%-98%] to 98% [95% CI, 96%-99%]) against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (eg, VE of 2 mRNA vaccines against symptomatic infection at 120-179 days was 86% [95% CI, 85%-88%] for dosing intervals <35 days, 92% [95% CI, 91%-93%] for 35-55 days, and 91% [95% CI, 90%-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals. Conclusions: Before the emergence of Omicron, VE of any 2-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes.

7.
JAMA Netw Open ; 5(9): e2232760, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2034686

ABSTRACT

Importance: The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses of COVID-19 vaccine, increased substantially following the emergence of the Omicron variant in Ontario, Canada. Understanding the estimated effectiveness of 2 or 3 doses of COVID-19 vaccine against outcomes associated with Omicron and Delta infections may aid decision-making at the individual and population levels. Objective: To estimate vaccine effectiveness (VE) against symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections. Design, Setting, and Participants: This test-negative case-control study used linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination, and health administration in Ontario, Canada. Participants were individuals aged 18 years or older who had COVID-19 symptoms or severe outcomes (hospitalization or death) and were tested for SARS-CoV-2 between December 6 and 26, 2021. Exposures: Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose. Main Outcomes and Measures: The main outcomes were symptomatic Omicron or Delta infection and severe outcomes (hospitalization or death) associated with infection. Multivariable logistic regression was used to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose compared with no vaccination. Estimated VE was calculated using the formula VE = (1 - [adjusted odds ratio]) × 100%. Results: Of 134 435 total participants, 16 087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 67 884 [59.5%] female). Estimated VE against symptomatic Delta infection decreased from 89% (95% CI, 86%-92%) 7 to 59 days after a second dose to 80% (95% CI, 74%-84%) after 240 or more days but increased to 97% (95% CI, 96%-98%) 7 or more days after a third dose. Estimated VE against symptomatic Omicron infection was 36% (95% CI, 24%-45%) 7 to 59 days after a second dose and 1% (95% CI, -8% to 10%) after 180 days or longer, but 7 or more days after a third dose, it increased to 61% (95% CI, 56%-65%). Estimated VE against severe outcomes was high 7 or more days after a third dose for both Delta (99%; 95% CI, 98%-99%) and Omicron (95%; 95% CI, 87%-98%). Conclusions and Relevance: In this study, in contrast to high estimated VE against symptomatic Delta infection and severe outcomes after 2 doses of COVID-19 vaccine, estimated VE was modest and short term against symptomatic Omicron infection but better maintained against severe outcomes. A third dose was associated with improved estimated VE against symptomatic infection and with high estimated VE against severe outcomes for both variants. Preventing infection due to Omicron and potential future variants may require tools beyond the currently available vaccines.


Subject(s)
COVID-19 , Hepatitis D , Influenza Vaccines , Influenza, Human , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Female , Humans , Influenza, Human/prevention & control , Male , Ontario/epidemiology , SARS-CoV-2
8.
Can J Public Health ; 113(6): 898-903, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2030411

ABSTRACT

SETTING: Rapid antigen screening can be effective in identifying infectious individuals in occupational settings to reduce transmission and outbreaks. We report results from a pilot project at the Greater Toronto Airports Authority (GTAA) and describe the operationalization. Toronto Pearson is a large international airport encompassing over 400 employers and, pre-pandemic, with approximately 50,000 employees. INTERVENTION: An employee screening program was piloted between March 8 and May 28, 2021, to implement rapid antigen testing for asymptomatic employees. Recruitment targeted enrolment of 400 employees and yielded participation of 717 from 58 companies. Employees were recommended to book three times per week for nasal swabs on site, and were tested on the Abbot PanbioTM rapid antigen test. No action was taken from a negative result, and if positive, the employee was told to isolate at home and obtain a confirmatory polymerase chain reaction test. OUTCOMES: A total of 5117 tests were performed on 717 individuals over 12 weeks; 5091 tests were negative (99.5%), and 22 individuals tested positive (3.1% positivity rate). One hundred twenty-four (17%) completed the post-participation survey. All respondents reported that testing did not change their behaviour at work with respect to public health recommendations, and only 1 (1%) reported behaviour change outside of work (socializing with family) as a result of the program. IMPLICATIONS: This pilot program identified 22 (3.1%) potentially infectious employees. Onsite testing was feasible and highly accepted by this group of employees who completed the survey. Education resulted in reasonable uptake and no substantial change in behaviour, although the survey response rate may limit generalizability. Home-based testing may facilitate larger recruitment.


RéSUMé: LIEU: Le dépistage antigénique rapide peut être efficace pour repérer les personnes infectieuses en milieu de travail afin de réduire la transmission et les éclosions. Nous rendons compte des résultats d'un projet pilote mené par l'Autorité aéroportuaire du Grand Toronto (GTAA) et nous en décrivons l'opérationnalisation. L'aéroport Toronto Pearson est un vaste aéroport international qui compte plus de 400 employeurs et, avant la pandémie, environ 50 000 employés. INTERVENTION: Un programme de dépistage au travail a fait l'objet d'un projet pilote entre le 8 mars et le 28 mai 2021 pour mettre en œuvre le dépistage antigénique rapide chez les employés asymptomatiques. Le recrutement visait l'inscription de 400 employés et a donné lieu à une participation de 717 personnes dans 58 entreprises. Il était recommandé aux employés de s'inscrire à un prélèvement nasal sur place trois fois par semaine; le test antigénique rapide d'Abbot PanbioTM était utilisé pour les prélèvements. Un résultat négatif ne donnait lieu à aucune mesure, mais si le résultat était positif, l'employé recevait l'instruction de s'isoler à la maison et d'obtenir un test de réaction de polymérisation en chaîne pour confirmer. RéSULTATS: En tout, 5 117 tests ont été effectués sur 717 personnes sur une période de 12 semaines; 5 091 tests (99,5 %) ont été négatifs, et 22 ont été positifs (taux de positivité de 3,1 %). Cent vingt-quatre personnes (17 %) ont répondu au sondage après la participation. Tous les répondants ont déclaré que le dépistage n'avait pas changé leur comportement au travail en ce qui a trait aux recommandations sanitaires, et une seule personne (1 %) a déclaré avoir changé ses comportements en dehors du travail (sa socialisation en famille) en raison du programme. CONSéQUENCES: Ce programme pilote a repéré 22 employés potentiellement infectieux (3,1 %). Le dépistage sur place était faisable et a été bien accepté par le groupe d'employés ayant répondu au sondage. La sensibilisation a donné lieu à une participation raisonnable sans modification sensible des comportements, mais le faible taux de réponse au sondage pourrait limiter la généralisabilité des résultats. Le dépistage à domicile pourrait favoriser un meilleur recrutement.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pilot Projects , COVID-19/diagnosis , Pandemics , COVID-19 Testing
10.
Arch Dis Child ; 2022 Jul 20.
Article in English | MEDLINE | ID: covidwho-1950051

ABSTRACT

OBJECTIVE: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. DESIGN: We conducted a community-based cross-sectional seroprevalence study in participants aged 0-18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. RESULTS: Post-first wave (June-August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10-14 years old) to 9.5% (participants 5-9 years old). By April-June 2021, this had increased to 19.9%, varying from 13.9% (participants 0-4 years old) to 32.7% (participants 15-18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. CONCLUSIONS: Approximately one-third of participants aged 15-18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. TRIAL REGISTRATION NUMBER: NCT04061382.

11.
Nat Microbiol ; 7(8): 1180-1188, 2022 08.
Article in English | MEDLINE | ID: covidwho-1931412

ABSTRACT

SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70-89 years, vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Membrane Glycoproteins/chemistry , Neutralization Tests , SARS-CoV-2/genetics , Viral Envelope Proteins/chemistry
12.
Front Immunol ; 13: 882515, 2022.
Article in English | MEDLINE | ID: covidwho-1903016

ABSTRACT

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.


Subject(s)
COVID-19 Vaccines , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , Adolescent , Adult , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Humans , RNA, Messenger , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
13.
Epidemiol Infect ; 150: e109, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1860261

ABSTRACT

The duration of immunity after first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. This is a retrospective population-based matched observational study where we identified the first polymerase chain reaction (PCR) positive of primary SARS-CoV-2 infection case tests between 1 March 2020 and 30 September 2020. Each case was matched by age, sex, upper tier local authority of residence and testing route to one individual testing negative in the same week (controls) by PCR. After a 90-day pre-follow-up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. We used a conditional logistic regression to analyse the results. There were 517 870 individuals in the matched cohort with 2815 reinfection cases and 12 098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (odds ratio (OR) 0.22, 0.21-0.23). Protection rose to 82% (OR 0.18, 0.17-0.19) after a sensitivity analysis excluded 933 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20-0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42-0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.


Subject(s)
COVID-19 , Reinfection , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , Cohort Studies , Humans , Polymerase Chain Reaction , Reinfection/epidemiology , Reinfection/prevention & control , Retrospective Studies , SARS-CoV-2/genetics
14.
Open Forum Infect Dis ; 9(5): ofac156, 2022 May.
Article in English | MEDLINE | ID: covidwho-1831308

ABSTRACT

Background: For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventive and/or therapeutic activity. Epidemiologic studies could complement laboratory-focused efforts to identify possible therapeutic agents. Methods: We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older individuals (≥65 years) in long-term care homes (LTCHs) and the community, between 15 January 2020 and 31 December 2020, across the province of Ontario, Canada. Results: A total of 26 121 cases and 2 369 020 controls from LTCHs and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared to be significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted odds ratio [OR], 0.91; standard P < .01, adjusted P < .01) and ß-blockers (weighted OR, 0.87; standard P < .01, adjusted P = .01), along with individual agents ranging from levetiracetam (weighted OR, 0.70; standard P < .01, adjusted P < .01) to fluoxetine (weighted OR, 0.86; standard P = .013, adjusted P = .198) to digoxin (weighted OR, 0.89; standard P < .01, adjusted P = .02). Conclusions: Using this epidemiologic approach, which can be applied to current and future pandemics, we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in coronavirus disease 2019 (COVID-19) and may warrant further validation. Some of these agents (eg, fluoxetine) have already been identified for their therapeutic potential.

16.
MethodsX ; 9: 101614, 2022.
Article in English | MEDLINE | ID: covidwho-1796315

ABSTRACT

Infectious disease transmission models often stratify populations by age and geographic patches. Contact patterns between age groups and patches are key parameters in such models. Arenas et al. (2020) develop an approach to simulate contact patterns associated with recurrent mobility between patches, such as due to work, school, and other regular travel. Using their approach, mixing between patches is greater than mobility data alone would suggest, because individuals from patches A and B can form contacts if they meet in patch C. We build upon their approach to address three potential gaps that remain, outlined in the bullets below. We describe the steps required to implement our approach in detail, and present step-wise results of an example application to generate contact matrices for SARS-CoV-2 transmission modelling in Ontario, Canada. We also provide methods for deriving the mobility matrix based on GPS mobility data (appendix).•Our approach includes a distribution of contacts by age that is responsive to the underlying age distributions of the mixing populations.•Our approach maintains different age mixing patterns by contact type, such that changes to the numbers of different types of contacts are appropriately reflected in changes to overall age mixing patterns.•Our approach distinguishes between two mixing pools associated with each patch, with possible implications for the overall connectivity of the population: the home pool, in which contacts can only be formed with other individuals residing in the same patch, and the travel pool, in which contacts can be formed with some residents of, and any other visitors to the patch.

17.
J Infect ; 84(5): 675-683, 2022 05.
Article in English | MEDLINE | ID: covidwho-1788130

ABSTRACT

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.


Subject(s)
COVID-19 Vaccines , COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Humans , Immunity , SARS-CoV-2 , Vaccine Efficacy
18.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1787289

ABSTRACT

Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (>65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada. Results 26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value <0.01, adjusted p-value <0.01) and beta-blockers (weighted OR 0.87, standard p-value <0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value <0.01, adjusted p-value <0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value <0.01, adjusted p-value 0.02). Conclusions Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.

19.
J Infect ; 84(6): 814-824, 2022 06.
Article in English | MEDLINE | ID: covidwho-1778314

ABSTRACT

OBJECTIVES: To monitor changes in seroprevalence of SARS-CoV-2 antibodies in populations over time and between different demographic groups. METHODS: A subset of practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network provided serum samples, collected when volunteer patients had routine blood tests. We tested these samples for SARS-CoV-2 antibodies using Abbott (Chicago, USA), Roche (Basel, Switzerland) and/or Euroimmun (Luebeck, Germany) assays, and linked the results to the patients' primary care computerised medical records. We report seropositivity by region and age group, and additionally examined the effects of gender, ethnicity, deprivation, rurality, shielding recommendation and smoking status. RESULTS: We estimated seropositivity from patients aged 18-100 years old, which ranged from 4.1% (95% CI 3.1-5.3%) to 8.9% (95% CI 7.8-10.2%) across the different assays and time periods. We found higher Euroimmun seropositivity in younger age groups, people of Black and Asian ethnicity (compared to white), major conurbations, and non-smokers. We did not observe any significant effect by region, gender, deprivation, or shielding recommendation. CONCLUSIONS: Our results suggest that prior to the vaccination programme, most of the population remained unexposed to SARS-CoV-2.


Subject(s)
COVID-19 , General Practitioners , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/epidemiology , England/epidemiology , Humans , Middle Aged , Primary Health Care , SARS-CoV-2 , Seroepidemiologic Studies , Young Adult
20.
Lancet Child Adolesc Health ; 6(6): 384-392, 2022 06.
Article in English | MEDLINE | ID: covidwho-1764066

ABSTRACT

BACKGROUND: Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England. METHODS: In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets. FINDINGS: Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection. INTERPRETATION: The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes. FUNDING: UK Health Security Agency.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/epidemiology , COVID-19 Testing , Child , England/epidemiology , Humans , Prospective Studies , Reinfection
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