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Our previously discovered monomeric aptamer for SARS-CoV-2 (MSA52) possesses a universal affinity for COVID-19 spike protein variants but is ultimately limited by its ability to bind only one subunit of the spike protein. The symmetrical shape of the homotrimeric SARS-CoV-2 spike protein presents the opportunity to create a matching homotrimeric molecular recognition element that is perfectly complementary to its structural scaffold, causing enhanced binding affinity. Here, we describe a branched homotrimeric aptamer with three-fold rotational symmetry, named TMSA52, that not only possesses excellent binding affinity but is also capable of binding several SARS-CoV-2 spike protein variants with picomolar affinity, as well as pseudotyped lentiviruses expressing SARS-CoV-2 spike protein variants with femtomolar affinity. Using Pd-Ir nanocubes as nanozymes in an enzyme-linked aptamer binding assay (ELABA), TMSA52 was capable of sensitively detecting diverse pseudotyped lentiviruses in pooled human saliva with a limit of detection as low as 6.3 × 10

Background Increased immune evasion by emerging SARS-CoV-2 variants and occurrence of breakthrough infections raise questions about whether COVID-19 vaccination status impacts SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the Omicron wave onset in Ontario, Canada. Methods Using linked provincial databases, we compared median Ct values across vaccination status among PCR-confirmed Omicron variant SARS-CoV-2 cases (sub-lineages B.1.1.529, BA.1 and BA.1.1) between December 6 and 30, 2021. Cases were presumed to be Omicron based on S-gene target failure (SGTF). We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex and symptom status. Results Of the 27,029 presumed Omicron cases in Ontario, the majority were among post-vaccination series completed cases (87.7%), followed by unvaccinated (8.1%), and post-booster dose cases (4.2%). Median Ct value for post-booster dose (18.3, Interquartile range (IQR): 15.4-22.3) was significantly higher than that for unvaccinated (17.9, IQR: 15.2-21.6, p = 0.018) and post-series completion cases (17.8, IQR: 15.3-21.5, p = 0.005). Post-booster dose cases remained associated with a significantly higher median Ct value than unvaccinated cases (p= Conclusions While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared to post-booster dose cases, further research is required to determine if a significant difference in secondary transmission exists between these groups.

Background Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. Methods Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010–2011 to 2018–2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. Results Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%–20%] and 17% [13%–21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10–1.21] and 1.15 [1.10–1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users. Conclusions Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

The Canadian Sentinel Practitioner Surveillance Network estimated vaccine effectiveness (VE) during the unusually early 2022/23 influenza A(H3N2) epidemic. Like vaccine, circulating viruses were clade 3C.2a1b.2a.2, but with genetic diversity affecting haemagglutinin positions 135 and 156, and reassortment such that H156 viruses acquired neuraminidase from clade 3C.2a1b.1a. Vaccine provided substantial protection with A(H3N2) VE of 54% (95% CI: 38 to 66) overall. VE was similar against H156 and vaccine-like S156 viruses, but with potential variation based on diversity at position 135.

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: −38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization’s decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresReceipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose.Main Outcomes and MeasuresThe 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%.ResultsOf 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 RelevanceIn 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.

The ability to rapidly diagnose, track, and disseminate information for SARS-CoV-2 is critical to minimize its spread. Here, we engineered a portable smartphone-based quantum barcode serological assay device for real-time surveillance of patients infected with SARS-CoV-2. Our device achieved a clinical sensitivity of 90% and specificity of 100% for SARS-CoV-2, as compared to 34% and 100%, respectively, for lateral flow assays in a head-to-head comparison. The lateral flow assay misdiagnosed ∼2 out of 3 SARS-CoV-2 positive patients. Our quantum dot barcode device has ∼3 times greater clinical sensitivity because it is ∼140 times more analytically sensitive than lateral flow assays. Our device can diagnose SARS-CoV-2 at different sampling dates and infectious severity. We developed a databasing app to provide instantaneous results to inform patients, physicians, and public health agencies. This assay and device enable real-time surveillance of SARS-CoV-2 seroprevalence and potential immunity.

Background: Outbreaks cause significant morbidity and mortality in healthcare settings. Current testing methods can identify specific viral respiratory pathogens, yet the approach to outbreak management remains general. Objectives: Our aim was to examine pathogen-specific trends in respiratory outbreaks, including how attack rates, case fatality rates and outbreak duration differ by pathogen between hospitals and long-term care (LTC) and retirement homes (RH) in Ontario. Methods: Confirmed respiratory outbreaks in Ontario hospitals and LTC/RH reported between September 1, 2007, and August 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Median attack rates and outbreak duration and overall case fatality rates of pathogen-specific outbreaks were compared in both settings. Results: Over the 10-year surveillance period, 9,870 confirmed respiratory outbreaks were reported in Ontario hospitals and LTC/RH. Influenza was responsible for most outbreaks (32% in LTC/RH, 51% in hospitals), but these outbreaks were shorter and had lower attack rates than most non-influenza outbreaks in either setting. Human metapneumovirus, while uncommon (

Contexte : Les éclosions provoquent une morbidité et une mortalité importantes dans les établissements de soins de santé. Les méthodes de dépistage actuelles permettent de cerner des agents pathogènes respiratoires viraux spécifiques, mais l’approche de la gestion des éclosions reste générale. Objectifs : Notre objectif était d’examiner les tendances spécifiques aux agents pathogènes dans les éclosions respiratoires, y compris la façon dont le taux d’attaque, le taux de létalité et la durée de l’éclosion diffèrent par agent pathogène entre les hôpitaux, et les établissements de soins de longue durée et les maisons de retraite en Ontario. Méthodes : Les éclosions d’infections respiratoires confirmées dans les hôpitaux et les établissements de soins de longue durée ou les maisons de retraite de l’Ontario signalées entre le 1er septembre 2007 et le 31 août 2017 ont été extraites du Système intégré d’information sur la santé publique (SIISP). Les taux d’attaque médians, la durée des éclosions et les taux généraux de létalité des éclosions spécifiques à un pathogène ont été comparés dans les deux types d’établissements. Résultats : Au cours de la période de surveillance de 10 ans, 9 870 éclosions respiratoires confirmées ont été signalées dans les hôpitaux et les établissements de soins de longue durée ou les maisons de retraite de l’Ontario. La grippe était à l’origine de la plupart des éclosions (32 % dans les établissements de soins de longue durée et les maisons de retraite, 51 % dans les hôpitaux), mais ces éclosions étaient plus courtes et présentaient des taux d’attaque inférieurs à ceux de la plupart des éclosions non grippales dans les deux types d’établissements. Le métapneumovirus humain, bien que peu fréquent (moins de 4 % des éclosions), présentait des taux de létalité élevés dans les deux types d’établissements. Conclusion : Les taux d’attaque et les taux de létalité variaient selon l’agent pathogène, tout comme la durée de l’éclosion. L’élaboration de conseils propres à la gestion des éclosions, qui tiennent compte de l’agent pathogène et de l’établissement de soins de santé, pourrait être utile pour limiter la charge des éclosions respiratoires.

The landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing is rapidly evolving. While serology testing has limited diagnostic capacity for acute infection, its role in providing population-based information on positivity rates and informing evidence-based decision making for public health recommendations is increasing. With the global availability of vaccines, there is increasing pressure on clinical laboratories to provide antibody screening and result interpretation for vaccinated and non-vaccinated individuals. Here we present the most up-to-date data on SARS-CoV-2 antibody timelines, including the longevity of antibodies, and the production and detection of neutralizing antibodies. Additionally, we provide practical guidance for clinical microbiology laboratories to both verify commercial serology assays and choose appropriate testing algorithms for their local populations.

CONTEXTE: Le deploiement de mesures de gestion des eclosions de SRAS-CoV-2 dans les etablissements de soins de longue duree en Ontario a permis d’en reduire la frequence et la gravite. Nous decrivons ici les donnees epidemiologiques et de laboratoire d’une de ces premieres eclosions en Ontario afin de determiner les facteurs associes a son importance et les impacts des interventions progressives de lutte contre les infections appliquees pendant la duree de l’eclosion. METHODES: Nous avons obtenu du bureau de sante la liste des cas et les donnees de l’eclosion afin de decrire les cas chez les residents et le personnel, leur gravite et leur distribution dans le temps et a l’interieur de l’etablissement touche. Quand elles etaient disponibles, nous avons obtenu des donnees concernant les echantillons soumis au laboratoire de Sante publique Ontario et effectue un sequencage complet et une analyse phylogenetique des echantillons viraux de l’eclosion. RESULTATS: Sur les 65 residents de l’etablissement de soins de longue duree, 61 (94 %) ont contracte le SRAS-CoV-2, le taux de letalite etant de 45 % (28/61). Parmi les 67 employes initiaux, 34 (51 %) ont contracte le virus, et aucun n’est decede. Lorsque l’eclosion a ete declaree, 12 employes, 2 visiteurs et 9 residents presentaient des symptomes. Parmi les residents, les cas se trouvaient dans 3 des 4 secteurs de l’etablissement. L’analyse phylogenetique a montre une forte similitude des sequences; une seule autre souche de SRAS-CoV-2 genetiquement distincte a ete identifiee chez un employe a la troisieme semaine de l’eclosion. Apres le deploiement de toutes les mesures de gestion de l’eclosion, aucun cas n’a ete identifie parmi les 26 nouveaux employes appeles en renfort. INTERPRETATION: La propagation rapide et non detectee du virus dans un etablissement de soins de longue duree a donne lieu a des taux eleves d’infection chez les residents et le personnel. L’application progressive de mesures de gestion apres le pic de l’eclosion a permis d’eviter la contamination du personnel appele en renfort et fait desormais partie des politiques a long terme de prevention des eclosions en Ontario.

BACKGROUND: The implementation of outbreak management measures has decreased the frequency and severity of SARS-CoV-2 outbreaks in Ontario long-term care homes. We describe the epidemiological and laboratory data from one of the first such outbreaks in Ontario to assess factors associated with its severity, and the impact of progressive interventions for infection control over the course of the outbreak. METHODS: We obtained line list and outbreak data from the public health unit to describe resident and staff cases, severity and distribution of cases over time and within the outbreak facility. Where available, we obtained data on laboratory specimens from the Public Health Ontario Laboratory and performed whole genome sequencing and phylogenetic analysis of viral specimens from the outbreak. RESULTS: Among 65 residents of the long-term care home, 61 (94%) contracted SARS-CoV-2, with a case fatality rate of 45% (28/61). Among 67 initial staff, 34 (51%) contracted the virus and none died. When the outbreak was declared, 12 staff, 2 visitors and 9 residents had symptoms. Resident cases were located in 3 of 4 areas of the home. Phylogenetic analysis showed tight clustering of cases, with only 1 additional strain of genetically distinct SARS-CoV-2 identified from a staff case in the third week of the outbreak. No cases were identified among 26 new staff brought into the home after full outbreak measures were implemented. INTERPRETATION: Rapid and undetected viral spread in a long-term care home led to high rates of infection among residents and staff. Progressive implementation of outbreak measures after the peak of cases prevented subsequent staff cases and are now part of long-term care outbreak policy in Ontario.

As of January 22, 2020, "disease caused by a novel coronavirus" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.

Depuis le 22 janvier 2020, la « maladie causée par un nouveau coronavirus » est devenue une maladie à déclaration obligatoire d’importance pour la santé publique en Ontario. Les bureaux de santé publique ont reçu des directives sur la saisie des patients testés pour le coronavirus responsable du syndrome respiratoire aigu sévère (SRAS-CoV-2), le virus causant la maladie à coronavirus 2019 (COVID-19), dans le système provincial d’information sur la santé publique. Entre le 22 janvier et le 22 février 2020, 359 personnes ont reçu un résultat négatif de test et trois cas de COVID-19 ont été confirmés. Parmi les personnes dont le résultat était négatif, 51 % étaient des femmes et 71 % avaient moins de 50 ans. Les symptômes les plus fréquemment signalés étaient la toux (55 %), la fièvre (37 %) et le mal de gorge (35 %). La majorité des personnes ont été testées dans les trois jours suivant l’apparition des symptômes, mais plus d’un quart d’entre elles l’ont été plus de sept jours après. Durant le premier mois de déclaration, les antécédents de voyage déclarés ont passé de la Chine à une proportion croissante de voyages ailleurs qu’en Chine.

BackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada.MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals.ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after ≥240 days, but increased to 97% (95%CI, 96-98%) ≥7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after ≥180 days, but increased to 61% (95%CI, 56-65%) ≥7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively).ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.

The Zika virus outbreak in the Americas prompted enhanced global surveillance due to the recognition of adverse neurological outcomes, including Guillain-Barre Syndrome, a novel but devastating congenital syndrome. Symptomatic Zika virus infection is clinically indistinguishable from other arboviral infections of the Americas such as chikungunya, dengue, and the more recently emerging Mayaro virus. We conducted laboratory surveillance for such arboviruses in ill returned travelers to the Americas between November 2015 and May 2016 by examining whole blood, malaria-negative specimens with noted travel history to the Americas by real-time and end-point PCR for the following targets: chikungunya (CHIKV), flaviviruses (Pan-Flavi), dengue virus types 1–4 (DEN1, DEN2, DEN3, DEN4), and Zika virus (ZIKV). End-point PCR was performed to detect Mayaro virus (MAYV). 1294 malaria-negative specimens were evaluated for compatible travel history. Of 224 enrolled specimens, 124 (55%) were from returned travelers to the Caribbean, while 66 (29.5%) were from Central America, and 34 (15.2%) from South America. Arboviral pathogens detected included: dengue (n = 3, 1.3%), Zika virus (n = 2, 0.9%), and unspecified flavivirus (n = 2, 0.9%). No cases of chikungunya or Mayaro were detected in the cohort. Common arboviruses circulating in the Americas were detected in over 3% of whole-blood malaria-free specimens from ill returned travelers, supporting the notion that during this time period, Zika virus was as commonly imported as dengue from this geographic region. Surveillance for other flaviviruses and alphaviruses including Mayaro virus is warranted to detect sentinel events, and inform priorities for diagnostic testing capacity.

SARS-CoV-2 variants of concern (VOC) are more transmissible and may have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax) and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC in Ontario, Canada, using a test-negative design study. We identified 682,071 symptomatic community-dwelling individuals who were tested for SARS-CoV-2, and 15,269 individuals with a COVID-19 hospitalization or death. Effectiveness against symptomatic infection ≥7 d after two doses was 89-92% against Alpha, 87% against Beta, 88% against Gamma, 82-89% against Beta/Gamma and 87-95% against Delta across vaccine products. The corresponding estimates ≥14 d after one dose were lower. Effectiveness estimates against hospitalization or death were similar to or higher than against symptomatic infection. Effectiveness against symptomatic infection was generally lower for older adults (≥60 years) than for younger adults (60 years) for most of the VOC-vaccine combinations. Our findings suggest that jurisdictions facing vaccine supply constraints may benefit from delaying the second dose in younger individuals to more rapidly achieve greater overall population protection; however, older adults would likely benefit most from minimizing the delay in receiving the second dose to achieve adequate protection against VOC.

Objective To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). Design Test negative design study. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. Interventions BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Main outcome measures Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. Results Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. Conclusions Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Background SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We sought to estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (COVID-19 hospitalization or death) caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs during December 2020 to May 2021. Methods We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Findings Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Protection against symptomatic infection caused by Beta/Gamma was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Vaccine effectiveness against hospitalization or death caused by all VOCs was generally higher than for symptomatic infection after partial vaccination for all three vaccines. Interpretation Our findings suggest that even a single dose of these 3 vaccines provide substantial protection against these 4 VOCs, and 2 doses likely provide higher protection. Jurisdictions facing vaccine supply constraints might consider delaying second doses to more rapidly achieve greater overall population protection.

The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of SARS-CoV2 is possessed by the three most common variants of concern - B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the COVID-19 pandemic.We developed and validated a single nucleotide polymorphism real-time reverse transcription polymerase chain reaction assay using allelic discrimination of the spike gene N501Ymutation to screen for potential variants of concern and differentiate them from wild-type SARS-CoV-2. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or wild-type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real time reverse transcriptase polymerase chain reaction assay. Our assay compared to sequencing, the gold standard for SNP detection and lineage identification, demonstrated clinical sensitivity of 100% for all 57 specimens displaying N501Y mutant, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wildtype and mutant. Clinical specificity was 100% in all 103 specimens typed as wild-type, with A23063 identified as wild-type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole genome sequencing which are time-consuming, labor-intensive and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole genome sequencing.