scholarly journals Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

2021 ◽  
Author(s):  
Koen B. Pouwels ◽  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
...  
Keyword(s):  
Single Dose ◽  
Natural Infection ◽  
Community Based ◽  
Symptomatic Infection ◽  
Younger Adults ◽  
Dosing Interval ◽  
Viral Burden ◽  
The Uk ◽  
Prior Infection ◽  
Similar Peak

AbstractThe effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. We investigated the effectiveness of the vaccines in a large community-based survey of randomly selected households across the UK. We found that the effectiveness of BNT162b2 and ChAd0x1 against any infections (new PCR positives) and infections with symptoms or high viral burden is reduced with the Delta variant. A single dose of the mRNA-1273 vaccine had similar or greater effectiveness compared to a single dose of BNT162b2 or ChAdOx1. Effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity following second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positives but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher among those vaccinated following a prior infection and younger adults. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.

scholarly journals Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

2021 ◽  
Author(s):  
Koen B. Pouwels ◽  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
...  
Keyword(s):  
Natural Infection ◽  
Absolute Difference ◽  
Community Based ◽  
Symptomatic Infection ◽  
The United Kingdom ◽  
Viral Burden ◽  
Alpha Variant ◽  
The Uk ◽  
Prior Infection ◽  
Similar Peak

AbstractThe effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2.

scholarly journals An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

2021 ◽  
Author(s):  
Sheila F Lumley ◽  
Gillian Rodger ◽  
Bede Constantinides ◽  
Nicholas Sanderson ◽  
Kevin K Chau ◽  
...  
Keyword(s):  
Cohort Study ◽  
Single Dose ◽  
Positive Result ◽  
Healthcare Workers ◽  
Natural Infection ◽  
Natural Immunity ◽  
Symptomatic Infection ◽  
Gene Target ◽  
Adjusted Incidence Rate ◽  
Induced Immunity

AbstractBackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.

scholarly journals Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada

2021 ◽  
Author(s):  
Hannah Chung ◽  
Siyi He ◽  
Sharifa Nasreen ◽  
Maria Sundaram ◽  
Sarah A Buchan ◽  
...  
Keyword(s):  
Older Adults ◽  
Logistic Regression ◽  
Single Dose ◽  
Outcome Measures ◽  
Vaccine Dose ◽  
Community Dwelling ◽  
Administrative Databases ◽  
Rt Pcr ◽  
Symptomatic Infection ◽  
Younger Adults

Objectives: To estimate the effectiveness of one and two doses of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design: Using a test-negative design study and linked laboratory, vaccination, and health administrative databases, we estimated adjusted vaccine effectiveness (aVE) against symptomatic infection and severe outcomes (hospitalization or death) using multivariable logistic regression. Setting: Ontario, Canada between 14 December 2020 and 19 April 2021. Participants: Community-dwelling adults aged ≥16 years who were tested for SARS-CoV-2 and had COVID-19 symptoms. Interventions: Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273 vaccine. Main outcome measures: Laboratory-confirmed SARS-CoV-2 identified by RT-PCR; hospitalization or death associated with SARS-CoV-2 infection. Results: Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received 1 or more vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. aVE against symptomatic infection 14 days or more after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14-20 days after the first dose to 71% (95%CI, 63 to 78%) at 35-41 days. aVE 7 days or more after receiving 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, aVE 14 days or more after receiving 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14-20 days to 91% (95%CI, 73 to 97%) at 35 days or more, whereas aVE 7 days or more after receiving 2 doses was 98% (95%CI, 88 to 100%). For adults aged 70 years and older, aVE estimates were lower after receiving 1 dose, but were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants. Conclusions: Two doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and severe outcomes. Effectiveness is lower after only a single dose, particularly for older adults shortly after the first dose.

scholarly journals Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK’s COVID-19 Infection Survey

2021 ◽  
Author(s):  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
Owen Gethings ◽  
...  
Keyword(s):  
Cohort Study ◽  
Single Dose ◽  
Population Based ◽  
Rt Pcr ◽  
Population Based Study ◽  
Viral Shedding ◽  
Asymptomatic Infections ◽  
The Uk ◽  
Prior Infection ◽  
Nose And Throat

AbstractObjectivesTo assess the effectiveness of COVID-19 vaccination in preventing SARS-CoV-2 infection in the community.DesignProspective cohort study.SettingThe UK population-representative longitudinal COVID-19 Infection Survey.Participants373,402 participants aged ≥16 years contributing 1,610,562 RT-PCR results from nose and throat swabs between 1 December 2020 and 3 April 2021.Main outcome measuresNew RT-PCR-positive episodes for SARS-CoV-2 overall, by self-reported symptoms, by cycle threshold (Ct) value (<30 versus ≥30), and by gene positivity (compatible with the B.1.1.7 variant versus not).ResultsOdds of new SARS-CoV-2 infection were reduced 65% (95% CI 60 to 70%; P<0.001) in those ≥21 days since first vaccination with no second dose versus unvaccinated individuals without evidence of prior infection (RT-PCR or antibody). In those vaccinated, the largest reduction in odds was seen post second dose (70%, 95% CI 62 to 77%; P<0.001).There was no evidence that these benefits varied between Oxford-AstraZeneca and Pfizer-BioNTech vaccines (P>0.9).There was no evidence of a difference in odds of new SARS-CoV-2 infection for individuals having received two vaccine doses and with evidence of prior infection but not vaccinated (P=0.89). Vaccination had a greater impact on reducing SARS-CoV-2 infections with evidence of high viral shedding Ct<30 (88% reduction after two doses; 95% CI 80 to 93%; P<0.001) and with self-reported symptoms (90% reduction after two doses; 95% CI 82 to 94%; P<0.001); effects were similar for different gene positivity patterns.ConclusionVaccination with a single dose of Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two doses of Pfizer-BioNTech, significantly reduced new SARS-CoV-2 infections in this large community surveillance study. Greater reductions in symptomatic infections and/or infections with a higher viral burden are reflected in reduced rates of hospitalisations/deaths, but highlight the potential for limited ongoing transmission from asymptomatic infections in vaccinated individuals.RegistrationThe study is registered with the ISRCTN Registry, ISRCTN21086382.

scholarly journals The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination

2021 ◽  
Author(s):  
Jia Wei ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
Ian Diamond ◽  
Ruth Studley ◽  
...  
Keyword(s):  
Single Dose ◽  
Peak Level ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Population Immunity ◽  
Previous Infection ◽  
Single Vaccination ◽  
Interim Measure ◽  
The Uk ◽  
Prior Infection

AbstractGiven high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single dose of ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults who received at least one vaccination, 13,404 (13.3%) had serological and/or PCR evidence of prior infection. Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations. In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose. Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.

scholarly journals Breadth of neutralising antibody responses to SARS-CoV-2 variants of concern is augmented by vaccination following prior infection: studies in UK healthcare workers and immunodeficient patients

2021 ◽  
Author(s):  
Angalee Nadesalingam ◽  
Diego Cantoni ◽  
David A Wells ◽  
Ernest T Aguinam ◽  
Matteo Ferrari ◽  
...  
Keyword(s):  
Single Dose ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Post Vaccination ◽  
Care Workers ◽  
Wide Range ◽  
Serological Data ◽  
The Uk ◽  
Prior Infection ◽  
Induced Immunity

A large portion of the UK general population has currently only received a single dose of a COVID-19 vaccination (either BNT162b2 (Pfizer) or AZD1222 (Vaxevria, AstraZeneca)), making it critical that we continue to track and understand the levels of protection against SARS-CoV-2 Variants of Concern (VOCs). We undertook a single-centre cross-sectional study in order to understand the variations in vaccine-induced immunity to the SARS-CoV-2 vaccine strain (B.1) and three major VOCs (B.1.1.7, B.1351 and P.1). We studied a cohort of outpatients with immunodeficiencies (IDPs) and health care workers (HCWs) based at the same critical care tertiary NHS Trust, following a single dose of either BNT162b2 or AZD1222 vaccines. Our serological data revealed either undetectable antibodies or low neutralising antibodies (nAbs) in IDPs, with only 5% and 3% showing detectable neutralisation of B.1.1.7 and B.1.351, respectively. Healthy HCWs without a prior SARS-CoV-2 infection demonstrated a wide range of nAb titres post-vaccination. However, their responses are significantly lower than HCWs with previous SARS-CoV-2 infection. Neutralisation of VOCs with the E484K mutation (B.1.351 and P.1) were consistently lower in HCWs in the absence of evidence of prior SARS-CoV-2 infection (p<0.001). Notably, in HCWs with prior SARS-CoV-2 infection, there is a significant increase of neutralising titres post-vaccination to all four strains, compared to their pre-vaccination neutralisation titres. This underscores the importance of vaccination even in populations that have been previously exposed, and also provides support for the hypothesis that a second-dose of vaccination will similarly boost immunity to greater protective levels in individuals without prior SARS-CoV-2 exposure. Overall, this serological nAb analysis after a single-dose of BNT162b2 or AZD1222 vaccination demonstrates a wide variety of responses, particularly against the VOCs, and suggests limited neutralisation-based protection in individuals with immunodeficiencies.

scholarly journals Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1347
Author(s):  
Claudia Maria Trombetta ◽  
Serena Marchi ◽  
Simonetta Viviani ◽  
Alessandro Manenti ◽  
Linda Benincasa ◽  
...  
Keyword(s):  
Natural Infection ◽  
Neutralizing Antibody ◽  
Original Strain ◽  
Immune Protection ◽  
Serum Samples ◽  
Symptomatic Infection ◽  
Neutralizing Activity ◽  
The United Kingdom ◽  
Antibody Titers ◽  
Pandemic Wave

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

scholarly journals Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom

2021 ◽  
Author(s):  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
Owen Gethings ◽  
...  
Keyword(s):  
United Kingdom ◽  
Viral Load ◽  
Threshold Value ◽  
Community Based ◽  
National Statistics ◽  
Private Households ◽  
The United Kingdom ◽  
Viral Burden ◽  
General Community ◽  
Nose And Throat

AbstractThe effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey—a large community-based survey of individuals living in randomly selected private households across the United Kingdom—to assess the effectiveness of the BNT162b2 (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54–68%) versus 66% (95% CI = 60–71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65–88%) versus 80% (95% CI = 73–85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines.

scholarly journals Reinfection Rates Among Patients Who Previously Tested Positive for Coronavirus Disease 2019: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Megan M Sheehan ◽  
Anita J Reddy ◽  
Michael B Rothberg
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Symptomatic Infection ◽  
Symptomatic Disease ◽  
Viral Shedding ◽  
History Of ◽  
Polymerase Chain ◽  
Prior Infection ◽  
Over Time

Abstract Background Protection afforded from prior disease among patients with coronavirus disease 2019 (COVID-19) infection is unknown. If infection provides substantial long-lasting immunity, it may be appropriate to reconsider vaccination distribution. Methods This retrospective cohort study of 1 health system included 150 325 patients tested for COVID-19 infection via polymerase chain reaction from 12 March 2020 to 30 August 2020. Testing performed up to 24 February 2021 in these patients was included. The main outcome was reinfection, defined as infection ≥90 days after initial testing. Secondary outcomes were symptomatic infection and protection of prior infection against reinfection. Results Of 150 325 patients, 8845 (5.9%) tested positive and 141 480 (94.1%) tested negative before 30 August. A total of 1278 (14.4%) positive patients were retested after 90 days, and 62 had possible reinfection. Of those, 31 (50%) were symptomatic. Of those with initial negative testing, 5449 (3.9%) were subsequently positive and 3191 of those (58.5%) were symptomatic. Protection offered from prior infection was 81.8% (95% confidence interval [CI], 76.6–85.8) and against symptomatic infection was 84.5% (95% CI, 77.9–89.1). This protection increased over time. Conclusions Prior infection in patients with COVID-19 was highly protective against reinfection and symptomatic disease. This protection increased over time, suggesting that viral shedding or ongoing immune response may persist beyond 90 days and may not represent true reinfection. As vaccine supply is limited, patients with known history of COVID-19 could delay early vaccination to allow for the most vulnerable to access the vaccine and slow transmission.

scholarly journals Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324789
Author(s):  
Nicholas A Kennedy ◽  
Simeng Lin ◽  
James R Goodhand ◽  
Neil Chanchlani ◽  
Benjamin Hamilton ◽  
...  
Keyword(s):  
Single Dose ◽  
Primary Outcome ◽  
Geometric Mean ◽  
Antibody Responses ◽  
Antibody Assay ◽  
Past Infection ◽  
White Ethnicity ◽  
Registration Number ◽  
Inflammatory Bowel ◽  
Prior Infection

ObjectiveDelayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.DesignAntibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.ResultsGeometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.ConclusionInfliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.Trial registration numberISRCTN45176516.

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