Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine
Open accessPublished version of a preprint
Abstract
BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).
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- Findingown data
A post hoc analysis estimated vaccine efficacy against the B.1.1.7 (alpha) variant at 86.3% (95% CI, 71.3 to 93.5).
“A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants.”
Quote in the paperSubstantial claim- The authors state this as an assumption: S-gene target failure on PCR indicates the presence of the B.1.1.7 variant.
- Findingown data
Among vaccine recipients, injection-site tenderness or pain was the most frequently reported solicited local adverse event after each dose.
“Among the vaccine recipients, the most commonly reported local adverse events were injection-site tenderness or pain after both the first dose (with 53.3% reporting tenderness and 29.3% reporting pain) and the second dose (76.4% and 51.2%, respectively), with most events being grade 1 (mild) or 2 (moderate) in severity and of a short mean duration (2.3 days of tenderness and 1.7 days of pain after”
Quote in the paperNot a substantial claim - Findingown data
All five severe Covid-19 cases occurred in the placebo arm.
“Five cases of severe infection were reported, all of which were in the placebo group.”
Quote in the paperNot a substantial claim - Findingown data
Solicited local adverse events were more frequent in younger vaccine recipients (18 to 64 years) than in older recipients (65 years or older).
“Solicited local adverse events were reported more frequently among younger vaccine recipients (18 to 64 years of age) than among older recipients (≥65 years).”
Quote in the paperNot a substantial claim - Findingown data
Two participants had grade 4 fever above 40°C, one after the first dose and one after the second.
“Two participants reported a grade 4 fever (>40 °C), one after the first dose and the other after the second dose.”
Quote in the paperNot a substantial claim
- Findingown data
After the second dose, solicited systemic adverse events were more common in the vaccine group than in the placebo group (64.0% vs. 30.0%).
“Solicited systemic adverse events were reportedly more frequently in the vaccine group than in the placebo group after both the first dose (45.7% vs. 36.3%)and the second dose (64.0% vs. 30.0%)(Fig. 2).”
Quote in the paperNot a substantial claim - Findingnone given
Reactogenicity was generally mild and transient.
“Reactogenicity was generally mild and transient.”
Quote in the paperNot a substantial claim - Findingown data
Younger vaccine recipients reported systemic adverse events more often than older vaccine recipients did.
“Systemic adverse events were reported more often by younger vaccine recipients than by older vaccine recipients and more often after the second dose than after the first dose.”
Quote in the paperNot a substantial claim - Findingown data
After the first dose, solicited systemic adverse events were more common in the vaccine group than in the placebo group (45.7% vs. 36.3%).
“Solicited systemic adverse events were reportedly more frequently in the vaccine group than in the placebo group after both the first dose (45.7% vs. 36.3%)and the second dose (64.0% vs. 30.0%)(Fig. 2).”
Quote in the paperNot a substantial claim - Findingown data
The second dose produced more frequent reports of systemic adverse events than the first dose did.
“Systemic adverse events were reported more often by younger vaccine recipients than by older vaccine recipients and more often after the second dose than after the first dose.”
Quote in the paperNot a substantial claim - Findingown data
After the first dose, solicited local adverse events were more common in the vaccine group than in the placebo group (57.6% vs. 17.9%).
“Solicited local adverse events were reported more frequently in the vaccine group than in the placebo group after both the first dose (57.6% vs. 17.9%) and the second dose (79.6% vs. 16.4%) (Fig. 2).”
Quote in the paperNot a substantial claim - Findingown data
After the second dose, solicited local adverse events were more common in the vaccine group than in the placebo group (79.6% vs. 16.4%).
“Solicited local adverse events were reported more frequently in the vaccine group than in the placebo group after both the first dose (57.6% vs. 17.9%) and the second dose (79.6% vs. 16.4%) (Fig. 2).”
Quote in the paperNot a substantial claim - Findingown data
Three vaccine recipients had grade 4 systemic adverse events.
“Grade 4 systemic adverse events were reported in 3 vaccine recipients.”
Quote in the paperNot a substantial claim - Findingown data
The same post hoc analysis estimated vaccine efficacy against non-B.1.1.7 variants at 96.4% (95% CI, 73.8 to 99.5).
“A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants.”
Quote in the paperSubstantial claim- The authors state this as an assumption: S-gene target failure on PCR indicates the presence of the B.1.1.7 variant.
- Findingown data
The myocarditis participant recovered fully after two days in hospital.
“The participant had a full recovery after 2 days of hospitalization.”
Quote in the paperNot a substantial claim - Findingown data
Unsolicited adverse events were more common in vaccine recipients than in placebo recipients (25.3% vs 20.5%).
“The frequency of unsolicited adverse events was higher among vaccine recipients than among placebo recipients (25.3% vs. 20.5%)”
Quote in the paperNot a substantial claim - Findingown data
Grade 4 fever (above 40°C) occurred in two participants, one after the first dose and one after the second.
“grade 4 fever (>40°C) was reported in 2 participants, with one event after the first dose and one after the second dose.”
Quote in the paperNot a substantial claim - Findingown data
Substantial efficacy was observed against all SARS-CoV-2 strains detected among trial participants.
“it is reassuring that substantial efficacy was shown against all the strains that were de-tected in the trial participants.”
Quote in the paperSubstantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
- Findingown data
Adverse events leading to discontinuation of trial participation occurred at similar rates in the vaccine and placebo groups (0.2% vs 0.2%).
“or participation in the trial (0.2% vs. 0.2%)”
Quote in the paperNot a substantial claim - Findingown data
In the same per-protocol population, such Covid-19 occurred in 96 placebo recipients, an incidence of 63.43 per 1000 person-years (95% CI, 45.19-89.03).
“and in 96 placebo recipients (63.43 per 1000 person-years; 95% CI, 45.19 to 89.03)”
Quote in the paperSubstantial claim - Findingown data
Only 5.7% of participants in this trial were non-White.
“only 5.7% of participants in the current trial were non-White.”
Quote in the paperNot a substantial claim - Findingown data
Severe Covid-19 occurred in five participants, all of whom were in the placebo group.
“Severe Covid-19 occurred in 5 participants, all in the placebo group.”
Quote in the paperSubstantial claim - Findingown data
Reactions were more common after the second dose.
“and more common after the second dose.”
Quote in the paperNot a substantial claim - Findingown data
Ten cases of mild, moderate, or severe Covid-19 occurred in participants aged 65 years or older: one in the vaccine group and nine in the placebo group.
“Ten cases of mild, moderate, or severe Covid-19 (1 in the vaccine group and 9 in the placebo group) were reported in participants who were 65 years of age or older”
Quote in the paperNot a substantial claim - Findingown data
No deaths were attributed to vaccination.
“no deaths were attributed to the receipt of the vaccine.”
Quote in the paperSubstantial claim - Findingown data
An independent safety monitoring committee judged the myocarditis event most likely to be viral myocarditis.
“an independent safety monitoring committee considered the event most likely to be viral myocarditis.”
Quote in the paperNot a substantial claim - Findingown data
The placebo-group death was in a 61-year-old man hospitalized 24 days after the first dose; he died four weeks later from complications of Covid-19 pneumonia and sepsis.
“The death in the placebo group occurred in a 61-year-old man who was hospitalized 24 days after the first dose; the participant died 4 weeks later after complications from Covid-19 pneumonia and sepsis.”
Quote in the paperNot a substantial claim - Findingown data
Medically attended adverse events occurred at similar rates in the vaccine and placebo groups (3.8% vs 3.9%).
“medically attended adverse events (3.8% vs. 3.9%)”
Quote in the paperSubstantial claim - Findingown data
Vaccine efficacy against the B.1.1.7 variant was 86.3% (95% CI, 71.3-93.5).
“Vaccine efficacy was 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 variant”
Quote in the paperSubstantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
- Findingown data
Among participants aged 65 years or older, overall vaccine efficacy was 88.9% (95% CI, 12.8-98.6).
“Among the participants who were 65 years of age or older, overall vaccine efficacy was 88.9% (95% CI, 12.8 to 98.6)”
Quote in the paperSubstantial claim - Findingown data
Vaccine efficacy against symptomatic Covid-19 was 89.7% (95% CI, 80.2-94.6).
“for a vaccine efficacy of 89.7% (95% CI, 80.2 to 94.6)”
Quote in the paperSubstantial claim - Findingown data
Potential immune-mediated medical conditions occurred at similar rates in the vaccine and placebo groups (<0.1% vs <0.1%).
“potential immune-mediated medical conditions (<0.1% vs. <0.1%)”
Quote in the paperNot a substantial claim - Findingown data
Serious adverse events occurred at similar rates in the vaccine and placebo groups (0.5% in each).
“serious adverse events (0.5% vs. 0.5%)”
- Also stated in: § Discussion · plain
“The incidence of serious adverse events was similar in the vaccine and placebo groups (0.5% in each)”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Injection-site tenderness and pain, fatigue, headache, and muscle pain were the most frequently reported local and systemic adverse events.
“Injection-site tenderness and pain, fatigue, headache, and muscle pain were the most commonly reported local and systemic adverse events.”
Quote in the paperNot a substantial claim - Findingown data
Starting 14 days after the first dose, vaccine efficacy among all participants was 83.4% (95% CI, 73.6-89.5).
“efficacy among all the participants starting 14 days after the first dose was 83.4% (95% CI, 73.6 to 89.5).”
Quote in the paperSubstantial claim - Findingown data
Adverse events leading to discontinuation of dosing occurred at similar rates in the vaccine and placebo groups (0.3% vs 0.3%).
“adverse events leading to discontinuation of dosing (0.3% vs. 0.3%)”
Quote in the paperNot a substantial claim - Findingown data
One related serious adverse event, myocarditis, occurred in a vaccine recipient three days after the second dose.
“One related serious adverse event (myocarditis) was reported in a vaccine recipient, which occurred 3 days after the second dose”
Quote in the paperNot a substantial claim - Findingown data
Reactogenicity was generally mild or moderate.
“Reactogenicity was generally mild or moderate”
Quote in the paperSubstantial claim - Findingown data
In the per-protocol population, virologically confirmed symptomatic mild, moderate, or severe Covid-19 with onset at least seven days after the second dose occurred in 10 vaccine recipients, an incidence of 6.53 per 1000 person-years (95% CI, 3.32-12.85).
“cases of virologically confirmed, symptomatic mild, moderate, or severe Covid-19 with an onset at least 7 days after the second dose occurred in 10 vaccine recipients (6.53 per 1000 person-years; 95% confidence interval [CI], 3.32 to 12.85)”
Quote in the paperSubstantial claim - Findingown data
Severe adverse events occurred at similar rates in the vaccine and placebo groups (1.0% vs 0.8%).
“with similar frequencies of severe adverse events (1.0% vs. 0.8%)”
Quote in the paperSubstantial claim - Findingown data
Adverse events of special interest related to Covid-19 occurred at similar rates in the vaccine and placebo groups (0.1% vs 0.3%).
“adverse events of special interest relevant to Covid-19 (0.1% vs. 0.3%)”
Quote in the paperSubstantial claim - Study design and conductown data
Because sequencing samples were unavailable, virus-strain characterization relied on PCR data alone.
“Samples were not available for sequencing, and virus-strain characterization was based on PCR data alone.12”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] source
Not checked in the free run.
- Study design and conductown data
Enrollment of approximately 15,000 participants, yielding 100 Covid-19 cases, was calculated to provide more than 95% power to detect vaccine efficacy of 70% or more.
“We determined that the enrollment of approximately 15,000 participants (resulting in a total number of 100 mild, moderate, or severe cases of Covid-19) would provide an overall power of more than 95% to determine a vaccine efficacy of 70% or more.”
Quote in the paperSubstantial claim - Study design and conductown data
In the per-protocol efficacy population, the two groups had similar distributions of demographic and clinical characteristics at baseline.
“The demographic and clinical characteristics of the participants at baseline were well balanced between the groups in the per-protocol efficacy population, in which 48.4% were women; 94.5% were White, 2.9% were Asian, and 0.4% were Black.”
Quote in the paperNot a substantial claim - Study design and conductown data
Covid-19 severity was assigned in a blinded manner using a prespecified automated algorithm.
“The severity of Covid-19 cases was determined in a blinded fashion on the basis of a prespecified, automated algorithm.”
Quote in the paperSubstantial claim - Study design and conductown data
The efficacy estimates came from a relatively short observation period, with a median of three months after the second dose.
“the efficacy estimates reported here are derived from a relatively short duration of observation (median, 3 months after dose 2).”
Quote in the paperSubstantial claim - Study design and conductown data
With approximately 7500 NVX-CoV2373 recipients, rare adverse events cannot be ruled out.
“Although approximately 7500 participants received NVX-CoV2373, it is not possible to exclude the occurrence of rare adverse events.”
Quote in the paperSubstantial claim - Study design and conductown data
The trial lacked sequencing data for viral isolates.
“A further limitation of the current trial is the lack of sequencing data on viral isolates”
Quote in the paperNot a substantial claim - Interpretationcitation
Vaccine efficacy was higher than the 70.4% reported for the ChAdOx1 nCoV-19 vaccine in a smaller phase 2-3 trial.
“Vaccine efficacy was greater than that associated with the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (70.4%) in a smaller phase 2-3 trial.16”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] source
Not checked in the free run.
- Study design and conductown data
The timing of case accumulation in the trial permitted a post hoc assessment of vaccine efficacy against strains including B.1.1.7.
“The timing of accumulated cases in this trial allowed for a post hoc assessment of vaccine efficacy against strains that included the B.1.1.7 variant”
Quote in the paperSubstantial claim - Interpretationcitation
Vaccine efficacy was higher than that reported for adenoviral vector vaccines.
“The vaccine efficacy was also greater than that reported for the adenoviral vector vaccines.5,6”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [5] source
Not checked in the free run.
- cites [6]
Not checked in the free run.
- Study design and conductnone given
The trial was not powered to assess efficacy against all circulating SARS-CoV-2 strains.
“Although the trial was not powered to assess efficacy for all the circulating SARS-CoV-2 strains”
Quote in the paperSubstantial claim - Interpretationown data
The trial results provide further evidence that a protein-based adjuvanted vaccine such as NVX-CoV2373 can prevent Covid-19 caused by B.1.1.7 or non-B.1.1.7 variants.
“The results of this trial provide further evidence that immunization with a protein-based, adjuvanted vaccine such as NVX-CoV2373 can prevent Covid-19 caused by either B.1.1.7 or non-B.1.1.7 variants.”
Quote in the paperSubstantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
- Study design and conductown data
The trial enrolled too few non-White participants to support meaningful conclusions about efficacy differences by race or ethnic group.
“Too few non-White participants were enrolled in the trial to draw meaningful conclusions about variations in efficacy on the basis of race or ethnic group.”
Quote in the paperSubstantial claim
- May combine two claims. 29
- Classified as probably not a substantial claim. 16
May combine two claims.
Findingown dataA total of 15,139 participants received at least one dose, and 14,039 met criteria for the per-protocol efficacy population.
“A total of 15,139 participants received at least one dose of NVX-CoV2373 (7569 participants) or placebo (7570 participants); 14,039 participants (7020 in the vaccine group and 7019 in the placebo group) met the criteria for the per-protocol efficacy population.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong the ten Covid-19 cases in the vaccine arm, there were no hospitalizations and no deaths.
“No hospitalizations or deaths were reported among the 10 cases in the vaccine group.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe per-protocol population had a median age of 56 years, and 27.9% of its members were at least 65 years old.
“The median age was 56 years, and 27.9% of the participants were 65 years of age or older (Table 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataRandomization included 15,187 participants, and the per-protocol efficacy population comprised 14,039 of them.
“A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMost solicited local adverse events in vaccine recipients were grade 1 or 2 and had a short mean duration.
“with most events being grade 1 (mild) or 2 (moderate) in severity and of a short mean duration (2.3 days of tenderness and 1.7 days of pain after the first dose and 2.8 and 2.2 days, respectively, after the second dose).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn a UK phase 3 randomized, observer-blinded, placebo-controlled trial, the NVX-CoV2373 vaccine prevented virologically confirmed symptomatic Covid-19 of mild, moderate, or severe grade, with onset at least a week after the second dose, in baseline-seronegative participants, with an efficacy of 89.7% (95% CI, 80.2 to 94.6).
“Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6).”
- Also stated in: § Abstract · plain
“A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
May combine two claims.
Findingown dataMost solicited systemic adverse events in vaccine recipients were grade 1 or 2 and had a short mean duration.
“with most events being grade 1 or 2 in severity and of a short mean duration (1.6, 1.6, and 1.8 days, respectively, after the first dose and 2.0, 1.8, and 1.9 days, respectively, after the second dose).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA total of 2310 participants were included in the solicited adverse event subgroup.
“A total of 2310 participants were included in the subgroup in which adverse events were solicited.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSerious adverse events occurred at a low incidence that was similar between the vaccine and placebo groups.
“The incidence of serious adverse events was low and similar in the two groups.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn the per-protocol population, 44.6% had one or more coexisting illnesses that the CDC classifies as raising risk for severe Covid-19.
“A total of 44.6% of the participants had at least one coexisting condition that had been defined by the Centers for Disease Control and Prevention as a risk factor for severe Covid-19.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo Covid-19 hospitalizations or deaths occurred among vaccine recipients in the per-protocol efficacy analysis.
“No hospitalizations or deaths from Covid-19 occurred among the vaccine recipients in the per-protocol efficacy analysis.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAfter the first dose, grade 3 fever (39-40°C) occurred in 0.4% of recipients; after the second dose, it occurred in 0.6%.
“Grade 3 fever (39°C to 40°C) was reported in 0.4% after the first dose and in 0.6% after the second dose”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataOf the five severe cases, one patient was hospitalized, three visited the emergency department, and one was cared for at home.
“Among these cases, 1 patient was hospitalized and 3 visited the emergency department; a fifth participant was cared for at home.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataTwo Covid-19-related deaths occurred, one in the vaccine group and one in the placebo group.
“Two deaths related to Covid-19 were reported, one in the vaccine group and one in the placebo group.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataA post hoc analysis of the primary endpoint identified the B.1.1.7 variant in 66 participants and a non-B.1.1.7 variant in 29; in 11 participants, PCR testing at a local hospital laboratory had not identified the variant.
“A post hoc analysis of the primary end point identified the B.1.1.7 variant in 66 participants and a non-B.1.1.7 variant in 29 participants; in 11 participants, PCR testing had been performed at a local hospital laboratory in which the variant had not been identified.”
Quote in the paperNot a substantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
May combine two claims.
Findingown dataThe vaccine-group death was in a 53-year-old man whose Covid-19 symptoms began seven days after the first dose; he was admitted to intensive care for respiratory failure from Covid-19 pneumonia and died 15 days after vaccination.
“The death in the vaccine group occurred in a 53-year-old man in whom Covid-19 symptoms developed 7 days after the first dose; he was subsequently admitted to the ICU for treatment of respiratory failure from Covid-19 pneumonia and died 15 days after vaccine adminis-tration.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong the 10 vaccine breakthrough cases, eight were caused by the B.1.1.7 variant, one by a non-B.1.1.7 variant, and one strain could not be identified.
“Of the 10 vaccine breakthrough cases, 8 were caused by the B.1.1.7 variant, 1 was caused by a non-B.1.1.7 variant, and 1 viral strain could not be identified.”
Quote in the paperNot a substantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
May combine two claims.
Findingown dataReactions were less common and milder in older participants.
“and reactions were less common and milder in older participants”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo cases of anaphylaxis or vaccine-associated enhanced Covid-19 were reported.
“No episodes of anaphylaxis or vaccine-associated enhanced Covid-19 were reported.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationThe B.1.1.7, P.1, and B.1.351 variants have been linked to greater transmissibility, more severe illness, and differing levels of escape from vaccine immunity.
“In late 2020, reports from the United Kingdom, Brazil, and South Africa confirmed the emergence of SARS-CoV-2 variants -B.1.1.7 (or alpha), P.1 (or gamma), and B.1.351(or beta), respectively -that have been associated with increased transmission, more severe disease, and varying degrees of immune avoidance to Covid-19 vaccines.[7][8][9]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7][8][9]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe B.1.1.7 variant was identified in southeast England in early October 2020 and spread to London and the rest of the UK during December 2020.
“In the United Kingdom, the B.1.1.7 variant was identified from genomic sequencing of samples obtained from patients with Covid-19 in the southeast of England in early October 2020.During December 2020, this new variant spread from the southeast region to London and the rest of the country.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductown dataParticipants were randomly assigned 1:1 using a centralized interactive response system and a pregenerated randomization schedule.
“Participants were randomly assigned in a 1:1 ratio to receive two 5-μg doses of NVX-CoV2373 or placebo (normal saline) administered 21 days apart by means of a centralized interactiveresponse system, according to a pregenerated randomization schedule.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAn independent safety monitoring committee performed safety oversight for vaccination-pause rules.
“Safety oversight for specific rules regarding a pause in vaccination was performed by an independent safety monitoring committee.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe North West-Greater Manchester Central Research Ethics Committee approved the trial protocol.
“The trial protocol was approved by the North West-Greater Manchester Central Research Ethics Committee.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll participants provided written informed consent.
“All the participants provided written informed consent.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationEarly clinical studies showed that NVX-CoV2373 was safe and produced a robust immune response in healthy adults.
“Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), which consists of 5 μg of a recombinant nanoparticle spike protein plus 50 μg of Matrix-M adjuvant, have shown that a two-dose regimen administered 21 days apart was safe and associated with a robust immune response in healthy adult participants.10,11”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe trial was conducted according to International Council for Harmonisation Good Clinical Practice guidelines.
“The trial was performed in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataRandomization was stratified by trial site and by age group (<65 years or ≥65 years).
“Randomization was stratified according to trial site and age (<65 years or ≥65 years).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe trial was observer-blinded.
“Because this was an observer-blinded trial, site personnel who were aware of trial-group assignments managed the logistics and preparation of the trial vaccines but were not involved in trialrelated assessments and did not have contact with the participants for data collection after vaccine administration.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThe two-dose regimen showed very high efficacy against severe disease, including hospitalization, intensive care admission, and death, similar to other licensed Covid-19 vaccines.
“the two-dose regimen of the NVX-CoV2373 vaccine showed very high efficacy against this end point, similar to that reported for other licensed Covid-19 vaccines.[3][4][5][6]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3][4][5][6]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAt the time of the report, B.1.1.7 was circulating widely outside the United Kingdom and was the most widespread strain reported in the United States.
“which is now circulating widely outside the United Kingdom and was the most widespread strain reported in the United States at the time of this report 15”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBy early 2021, several vaccine candidates had been shown to be safe and effective in preventing Covid-19.
“By early 2021, several vaccine candidates had emerged as safe and effective in preventing coronavirus disease 2019 (Covid-19), findings that supported the emergency use of these vaccines around the world.[3][4][5][6]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3][4][5][6]
Not checked in the free run.
May combine two claims.
Interpretationown dataA two-dose NVX-CoV2373 regimen given 21 days apart was safe and 89.7% effective against symptomatic Covid-19 caused by B.1.1.7 and non-B.1.1.7 variants.
“A two-dose regimen of the NVX-CoV2373 vaccine administered 21 days apart was found to be safe and 89.7% effective against symptomatic Covid-19 caused by both B.1.1.7 and non-B.1.1.7 variants.”
Quote in the paperSubstantial claim- Rests on an assumption: S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
May combine two claims.
PremisecitationNVX-CoV2373 has shown efficacy against the B.1.351 variant, though lower (51.0%) than against B.1.1.7 and non-B.1.1.7 strains.
“the NVX-CoV2373 vaccine has also shown efficacy against the B.1.351variant, albeit at a lower level (51.0%) than has been shown for the B.1.1.7 and non-B.1.1.7 strains.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe B.1.1.7 variant is more transmissible and has a higher case fatality rate than earlier strains.
“This variant is known to be more transmissible and to be associated with a higher case fatality rate than previous strains.7”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAll 15,139 participants who received at least one dose before the final efficacy data cutoff were included in the unsolicited adverse event assessment.
“All 15,139 participants who had received at least one dose of vaccine or placebo through the data cutoff date of the final efficacy analysis were assessed for unsolicited adverse events.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataAlthough the trial was not designed to assess efficacy after one dose, NVX-CoV2373 provided first-dose protection in a range similar to other Covid-19 vaccines.
“although this trial was not designed to assess vaccine efficacy after a single dose, NVX-CoV2373 provided levels of protection after the first dose in a range similar to those of other Covid-19 vaccines.[3][4][5][6]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3][4][5][6]
Not checked in the free run.
May combine two claims.
InterpretationcitationThe 96.4% efficacy against non-B.1.1.7 strains, most of which were prototype, is similar to the 95.0% efficacy reported for the BNT162b2 mRNA vaccine and the 94.1% efficacy for the mRNA-1273 vaccine.
“the efficacy estimate of 96.4% against the non-B.1.1.7 strains (the majority of which were the prototype strain 17 ) is similar to the efficacy of 95.0% reported against this strain for the BNT161b2 messenger RNA (mRNA) vaccine (BioNTech/Pfizer) and the efficacy of 94.1% for the mRNA-1273 vaccine (Moderna).3,4”
Quote in the paperNot a substantial claim0 of 2 sources checked
The authors state this as an assumption.
S-gene target failure on PCR indicates the presence of the B.1.1.7 variant.
“Results were described as being S-gene negative (or having S-gene target failure) if the PCR target of the spike-protein gene was not detected but other PCR targets (i.e., N and ORF1ab genes) were detected; such results were presumed to indicate the presence of B.1.1.7 variants.”
The paper relies on this without support.
S-gene target failure detected by the TaqPath assay reliably indicates the presence of the B.1.1.7 variant.
“although the use of S-gene target failure, as detected by the TaqPath assay, has proved to be a reliable proxy for the presence of B.1.1.7 variants.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a post-hoc analysis of a NVX-CoV2373 clinical trial, vaccine efficacy was 86.3% against Alpha variants compared with 96.4% against non-Alpha variants.
“In a post-hoc analysis of a NVX-CoV2373 clinical trial, vaccine efficacy was 86.3% against Alpha variants compared with 96.4% against non-Alpha variants 212 (TABLe 2).”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [212]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Flow diagram mislabels exclusions as safety-population exclusions
MinorThe flow diagram says 549 vaccine recipients were excluded from the safety population, but the paper defines that population as everyone who received at least one dose. Those 549 recipients are included in its safety-population count and excluded when deriving the per-protocol population.
“549 Were excluded from the safety population 399 Were seropositive before 7 days after dose 2 102 Received only 1 dose 48 Had major protocol deviation, missed dose, or had censoring event 7020 Were included in the per-protocol population”
“The full analysis set (safety population) included all the participants who had undergone randomization and received at least one dose of the NVX-CoV2373 vaccine or placebo, regardless of protocol violations or missing data.”
Upper confidence limit differs for non-B.1.1.7 efficacy
MinorThe abstract and Figure 4 give an upper 95% confidence limit of 99.5%, whereas the results text gives 99.4% for the same 96.4% efficacy estimate.
“96.4% (95% CI, 73.8 to 99.4)”
“96.4% (95% CI, 73.8 to 99.5)”
Two confidence intervals are given for efficacy in older participants
MinorThe text and Figure 4 report the same 88.9% efficacy estimate for participants aged 65 or older, but give different 95% confidence intervals.
“Among the participants who were 65 years of age or older, overall vaccine efficacy was 88.9% (95% CI, 12.8 to 98.6)”
“88.9 (20.2 to 99.7)”
Cites
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · see citing works
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
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A Modified Poisson Regression Approach to Prospective Studies with Binary Data
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Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
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Self-citationPhase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
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Self-citationChallen, R., Brooks-Pollock, E., Read, J. M., Dyson, L., Tsaneva-Atanasova, K., & Danon, L. (2021) · BMJ · doi:10.1136/bmj.n579 · Cited by 776 · see citing works
Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant
Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., Lalloo, U., Masilela, M. S. L., Moodley, D., Hanley, S., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103055 · Cited by 625 · see citing works
Self-citationPreliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant
Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., Lalloo, U., Masilela, M. S. L., Moodley, D., Hanley, S., et al. (2021) · doi:10.1101/2021.02.25.21252477 · Cited by 625 · see citing works
Self-citationEmary, K. R. W., Golubchik, T., Aley, P. K., Ariani, C. V., Angus, B., Bibi, S., Blane, B., Bonsall, D., Cicconi, P., Charlton, S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00628-0 · Cited by 603 · see citing works
Self-citationSARS-CoV-2 Variants of Concern in the United States—Challenges and Opportunities
Walensky, R. P., Walke, H. T., & Fauci, A. S. (2021) · JAMA · doi:10.1001/jama.2021.2294 · Cited by 319 · see citing works
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Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults
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Self-citationCould new COVID variants undermine vaccines? Labs scramble to find out
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Flagged first, then by citations
Cited by
Sorted by citations
The biological and clinical significance of emerging SARS-CoV-2 variants
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- Authors
- Heath, P. T., Galiza, E. P., Baxter, D. N., Boffito, M., Browne, D., Burns, F., Chadwick, D. R., Clark, R., Cosgrove, C., Galloway, J., Goodman, A. L., Heer, A., Higham, A., Iyengar, S., Jamal, A., Jeanes, C., Kalra, P. A., Kyriakidou, C., McAuley, D. F., Meyrick, A., Minassian, A. M., Minton, J., Moore, P., Munsoor, I., Nicholls, H., Osanlou, O., Packham, J., Pretswell, C. H., San Francisco Ramos, A., Saralaya, D., Sheridan, R. P., Smith, R., Soiza, R. L., Swift, P. A., Thomson, E. C., Turner, J., Viljoen, M. E., Albert, G., Cho, I., Dubovsky, F., Glenn, G., Rivers, J., Robertson, A., Smith, K., & Toback, S.
- Affiliations
- St George's, University of London (GB)
- From the Vaccine Institute, St. George’s, University of London, and St. George’s University Hospitals NHS Foundation Trust (P.T.H., E.P.G., C.C., A.S.F.R.), Chelsea, Westminster Hospital NHS Foundation Trust and Imperial College London (M.B.), the Institute for Global Health, University College London, and Royal Free London NHS Foundation Trust (F.B.), the Centre for Rheumatic Disease, Kings College London (J.G.), the Department of Infectious Diseases, Guy’s and St. Thomas’ NHS Foundation Trust, MRC Clinical Trials Unit at University College London (A.L.G.), and Renal Services, Epsom and St. Helier University Hospitals NHS Trust (P.A.S.), London, Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport (D.N.B.), Royal Cornwall Hospitals NHS Trust, Truro (D.B.), Centre for Clinical Infection, South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (D.R.C.), Layton Medical Centre, Blackpool (R.C.), Lakeside Healthcare Research, Lakeside Surgeries, Corby (A. Heer), Un...
- Corresponding author
- Toback, Seth
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-09-23
- Volume
- 385
- Issue
- 13
- Pages
- 1172-1183
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8262625
- OpenAlex
- W3175514659
- Cited by
- 1,085
- References
- 14
- Citations by year
- 2026: 49 · 2025: 114 · 2024: 158 · 2023: 248 · 2022: 382 · 2021: 134
- FWCI
- 73.24
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Radar (Oxford Brookes University) (submittedVersion)
- Funders
- Novavax
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- NVX-CoV2373, Novavax, COVID-19 vaccines, SARS-CoV-2, Matrix-M adjuvant, spike protein, vaccine efficacy, vaccine safety, reactogenicity, B.1.1.7 variant, SARS-CoV-2 variants, immunogenicity, healthy adults
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adolescent, Adult, Aged, Aged, 80 and over, Humans, Injections, Intramuscular, Middle Aged, Vaccines, Synthetic, Single-Blind Method, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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