CoChat
Sign Up
Cited by 68SARS-CoV-2 and COVID-19 ResearchVaccine Coverage and HesitancyCOVID-19 epidemiological studies

Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore

Open access
Ng, Oon Tek, Marimuthu, Kalisvar, Lim, Nigel, Lim, Ze Qin, Thevasagayam, Natascha May, Koh, Vanessa, Chiew, Calvin J., Ma, Stefan +10 more·2022·JAMA Network Open
DOI 10.1001/jamanetworkopen.2022.28900PMC PMC9419014
Open this paper in CoChat — free accountOpen PDF

Abstract

Importance: Assessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies. Objective: To determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave. Design, Setting, and Participants: This cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded. Exposures: Two or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV. Main Outcomes and Measures: Notified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression. Results: Among 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from –2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%). Conclusions and Relevance: Booster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.

AI snapshot

Written from the paper’s full text.

TL;DR

In a nationwide Singapore cohort of 2,441,581 adults aged 30 years or older during the Omicron wave, mRNA booster doses increased protection against severe COVID-19, with 87.4% effectiveness 15–60 days after boosting and no waning through 6 months. Protection against confirmed Omicron infection was modest (31.7%–41.3% shortly after mRNA boosting) and waned rapidly, while 3-dose inactivated vaccines gave 69.6% protection against severe disease.

Key findings

  • Among 2,441,581 adults, mRNA booster effectiveness against confirmed Omicron infection 15–60 days after the third dose was 41.3% (95% CI, 39.4%–43.1%) for homologous mRNA-1273, 34.9% (33.0%–36.8%) for PPM, 35.6% (32.8%–38.3%) for MMP, and 31.7% (30.0%–33.4%) for homologous BNT162b2; effectiveness waned rapidly, falling more than 4 months after boosting to 14.6% (11.0%–18.0%) for mRNA-1273, 3.7% (0.03%–7.2%) for PPM, 9.7% (2.7%–16.3%) for MMP, and −2.8% (−5.4%–0.3%) for BNT162b2.
  • mRNA booster effectiveness against severe COVID-19 was 87.4% (95% CI, 83.3%–90.5%) 15–60 days after boosting and 87.2% (84.2%–89.7%) 5–6 months after boosting, with no significant decline over time; homologous mRNA-1273 boosting gave 97.5% (89.7%–99.4%) and homologous BNT162b2 gave 85.2% (80.2%–88.9%) at 15–60 days.
  • Three-dose inactivated SARS-CoV-2 vaccination had estimated booster effectiveness against severe COVID-19 of 69.6% (95% CI, 48.7%–81.9%) 15–330 days after the third dose; the adjusted IRR for severe COVID-19 was 0.30 (95% CI, 0.18–0.51) versus 5 months after 2-dose mRNA vaccination, while 2-dose inactivated vaccination had an adjusted IRR of 1.81 (95% CI, 1.20–2.74) 15–60 days after the second dose.
  • Incidence rates were 162 confirmed infections per 100,000 person-days among 2-dose mRNA recipients, 195 among 3-dose mRNA recipients, 193 among 2-dose inactivated vaccine recipients, and 213 among 3-dose inactivated vaccine recipients.

Methods

  • Retrospective population-based cohort using Singapore Ministry of Health’s official COVID-19 database; included Singapore citizens or permanent residents aged 30 years and older after October 10, 2021, who received 2 or 3 doses of mRNA vaccines (Pfizer-BioNTech or Moderna) or inactivated vaccines (Sinovac or Sinopharm).
  • Excluded unvaccinated and partially vaccinated individuals, migrant workers in dormitories, individuals with known SARS-CoV-2 infection before December 27, 2021, and reinfections; analysis covered December 27, 2021, through March 10, 2022, when Omicron was predominant, retaining 2,441,581 persons.
  • Outcomes were notified SARS-CoV-2 infection and severe COVID-19 (oxygen supplementation, ICU admission, or death); binomial regression with log-link estimated incidence-rate ratios/relative risks, adjusted for age, sex, housing status, calendar day, vaccine type and combination, and time since last dose, with 121–150 days after 2-dose mRNA vaccination as the reference.

Limitations

  • Stated: findings apply only to adults aged 30 years and older; the study did not control for individual-level exposure risk factors, had no negative COVID-19 test results or testing-frequency data, no symptom data, and no comorbidity data; unreported infections and reinfections could be misclassified, severe cases diagnosed near the end of follow-up could be misclassified as nonsevere, and BA.1/BA.2 sublineages could not be fully differentiated.
  • Stated: vaccine mandates enforced workplace and movement restrictions and could have reduced infection risk, though these mandates did not differentiate between 2-dose and 3-dose mRNA recipients; because of vaccine-differentiated measures, vaccine effectiveness could not be estimated using unvaccinated individuals as the reference group.
  • Evident from the text: some subgroup estimates were imprecise because of few severe events, including zero severe COVID-19 cases in the MMP 15–60-day group and wide confidence intervals for inactivated and heterologous booster estimates.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jamanetworkopen.2022.28900

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 13 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Compared with 5 months after 2-dose mRNA COVID-19 vaccination, adjusted IRR of severe COVID-19 15-60 days following second dose of inactivated COVID-19 vaccination was 1.81 (95% CI, 1.20-2.74; P = .005).

    “Compared with 5 months after 2-dose mRNA COVID-19 vaccination, the adjusted IRR of severe COVID-19 15 to 60 days following the second dose of inactivated COVID-19 vaccination was 1.81 (95% CI, 1.20-2.74; P = .005)”
    Quote in the paperSubstantial claim
  • Findingown data

    The incidence rate of confirmed infections among 2-dose mRNA vaccine recipients was 162 confirmed infections per 100,000 person-days at risk.

    “The incidence rate of confirmed infections among 2-dose mRNA vaccine recipients was 162 confirmed infections per 100 000 person-days at risk.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Notified SARS-CoV-2 infections recorded in the Singapore Ministry of Health database accurately reflect the incidence of SARS-CoV-2 infection in the study population.
  • Findingown data

    More than 4 months after the third dose, the booster effectiveness against confirmed infection of homologous mRNA-1273 boosting was estimated at 14.6% (95% CI, 11.0% to 18.0%).

    “More than 4 months after the third dose, the booster effectiveness against confirmed infection of homologous mRNA-1273 boosting was estimated at 14.6% (95% CI, 11.0% to 18.0%).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Notified SARS-CoV-2 infections recorded in the Singapore Ministry of Health database accurately reflect the incidence of SARS-CoV-2 infection in the study population.
    • Rests on an assumption: After adjustment for age, sex, housing status, and calendar day, there is no unmeasured confounding of the association between vaccination status and SARS-CoV-2 infection or severe COVID-19.
  • Findingown data

    Comparing 3-dose inactivated SARS-CoV-2 vaccines with mRNA vaccines, the 3-dose inactivated vaccine was less protective against confirmed infection than 2 or 3 doses of mRNA vaccines.

    “Comparing 3-dose inactivated SARS-CoV-2 vaccines with mRNA vaccines, we found that the 3-dose inactivated vaccine was less protective against confirmed infection than 2 or 3 doses of mRNA vaccines.”
    Quote in the paperSubstantial claim
  • Findingown data

    Protection against confirmed infection for both second and third mRNA dose waned rapidly at similar rates.

    “Protection against confirmed infection for both second and third mRNA dose waned rapidly at similar rates.”
    Quote in the paperSubstantial claim
  • May combine two claims. 8
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    Against severe COVID-19, the 3-dose inactivated vaccine provided more protection than 2-dose mRNA vaccination but less than 3-dose mRNA vaccination.

    “Against severe COVID-19, the 3-dose inactivated vaccine provided more protection than 2-dose mRNA vaccination but less than 3-dose mRNA vaccination.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    3-dose inactivated SARS-CoV-2 vaccination provided greater protection compared with 2-dose mRNA vaccination against severe COVID-19 but less protection compared with 3-dose mRNA vaccination against severe COVID-19.

    “Nonetheless, 3-dose inactivated SARS-CoV-2 vaccination provided greater protection compared with 2-dose mRNA vaccination against severe COVID-19 but less protection compared with 3-dose mRNA vaccination against severe COVID-19.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In our cohort, we did not detect any significant waning of booster protection against severe COVID-19 up to 6 months after the third mRNA vaccine dose or any differences in protection against severe COVID-19 comparing the different mRNA boosting combinations.

    “In our cohort, we did not detect any significant waning of booster protection against severe COVID-19 up to 6 months after the third mRNA vaccine dose or any differences in protection against severe COVID-19 comparing the different mRNA boosting combinations.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the cohort of 2,441,581 individuals aged 30 years or more, estimated mRNA booster effectiveness against Omicron-confirmed infection ranged from 31.7% to 41.3% in the 15 to 60 days after the third dose.

    “In this cohort study including 2 441 581 individuals aged 30 years or more, the estimated effectiveness of the mRNA booster against Omicron-confirmed infections ranged from 31.7% to 41.3% with rapid waning over time.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Notified SARS-CoV-2 infections recorded in the Singapore Ministry of Health database accurately reflect the incidence of SARS-CoV-2 infection in the study population.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An mRNA booster is required in Singapore following completion of a 3-dose inactivated vaccine series to qualify for full vaccination status fulfilling vaccine mandates.

    “As such, an mRNA booster is required in Singapore following completion of a 3-dose inactivated vaccine series to qualify for full vaccination status fulfilling vaccine mandates.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Information on vaccination-differentiated safe management measures (SMMs). July 19, 2022. Accessed March 22, 2022. https://file.go.gov.sg/vdsmminfo.pdf

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Recent data from Israel demonstrated that among persons 60 years or older, a fourth dose of BNT162b2 increased protection against severe COVID-19.

    “Recent data from Israel demonstrated that among persons 60 years or older, a fourth dose of BNT162b2 increased protection against severe COVID-19.27”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Bar-On YM, Goldberg Y, Mandel M,. Protection by a fourth dose of BNT162b2 against Omicron in Israel. NEJM. 2022; 386(18): 1712- 1720. doi: 10.1056/NEJMoa2201570 35381126 PMC9006780

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A test-negative study from England determined that booster mRNA vaccination was associated with increased protection against symptomatic infection and severe COVID-19 with waning of protection observed 1 to 2 months following booster vaccination.

    “Similar to our results, a test-negative study from England determined that booster mRNA vaccination was associated with increased protection against symptomatic infection and severe COVID-19 with waning of protection observed 1 to 2 months following booster vaccination.5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Andrews N, Stowe J, Kirsebom F,. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med. 2022; 386(16): 1532- 1546. doi: 10.1056/NEJMoa2119451 35249272 PMC8908811 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The final 7 days of data in the period under study were omitted from the analysis when computing risk ratios for severe disease to account for the limited observation time for these individuals.

    “The final 7 days of data in the period under study were omitted from the analysis when computing risk ratios for severe disease to account for the limited observation time for these individuals.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Individuals who received a booster vaccination left the at-risk pool for 15 days to account for the build-up of protection and then reentered the at-risk pool thereafter.

    “Individuals moved between categories during the period of analysis; if they received a booster vaccination, they left the at-risk pool for 15 days (to account for the build-up of protection) then reentered the at-risk pool thereafter.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

    “This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    Vaccine mandates enforced workplace and movement restrictions on individuals not meeting definitions for full vaccination and could have reduced infection risk.

    “Vaccine mandates enforced workplace and movement restrictions on individuals not meeting definitions for full vaccination and could have reduced infection risk.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Vaccine mandates enforced workplace and movement restrictions on individuals not meeting definitions for full vaccination.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In Singapore, a fourth mRNA vaccine dose is currently recommended for selected subpopulations, specifically persons aged 80 years and older, persons living in aged care facilities and persons with medical risk factors for severe COVID-19.

    “In Singapore, a fourth mRNA vaccine dose is currently recommended for selected subpopulations, specifically persons aged 80 years and older, persons living in aged care facilities and persons with medical risk factors for severe COVID-19.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Singapore Ministry of Health. Expert Committee On Covid-19 Vaccination Recommends A Second Booster Dose of mRNA Covid-19 Vaccine for Persons Aged 80 Years and Above, Five Months After Completion of the First Booster. March 24, 2022. Accessed April 5, 2022. https://www.moh.gov.sg/news-highlights/details/expert-committee-on-covid-19-vaccination-recommends-a-second-booster-dose-of-mrna-covid-19-vaccine-for-persons-aged-80-years-and-above-five-months-after-completion-of-the-first-booster

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A prior study from Qatar determined a booster effectiveness of 76.5% (95% CI, 55.9%-87.5%) against Omicron-related hospitalization and death.

    “A prior study from Qatar determined a booster effectiveness of 76.5% (95% CI, 55.9%-87.5%) against Omicron-related hospitalization and death.4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Abu-Raddad LJ, Chemaitelly H, Ayoub HH,. Effect of mRNA vaccine boosters against SARS-CoV-2 Omicron infection in Qatar. N Engl J Med. 2022; 386(19): 1804- 1816. doi: 10.1056/NEJMoa2200797 35263534 PMC8929389 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Data from the US Centers for Disease Control and Prevention VISION network demonstrated waning protection of 3-dose vaccination against hospitalization in the US.

    “Data from the US Centers for Disease Control and Prevention VISION network (Virtual Network to Investigate Risk of COVID-19–Associated Outcomes and COVID-19 Vaccine Effectiveness Using Integrated Medical and Public Health Records) also demonstrated waning protection of 3 dose vaccination against hospitalization in the US.7”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Ferdinands JM, Rao S, Dixon BE,. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against COVID-19–associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance—VISION Network, 10 states, August 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022; 71(7): 255- 263. doi: 10.15585/mmwr.mm7107e2 35176007 PMC8853475 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Population studies from the UK and Qatar have demonstrated that receipt of a third (booster) dose of mRNA COVID-19 vaccine increases protection against Omicron infection and severe disease.

    “Population studies from the UK and Qatar have demonstrated that receipt of a third (booster) dose of mRNA COVID-19 vaccine increases protection against Omicron infection and severe disease.4,5”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Abu-Raddad LJ, Chemaitelly H, Ayoub HH,. Effect of mRNA vaccine boosters against SARS-CoV-2 Omicron infection in Qatar. N Engl J Med. 2022; 386(19): 1804- 1816. doi: 10.1056/NEJMoa2200797 35263534 PMC8929389 source

      Not checked in the free run.

    • cites [5] Andrews N, Stowe J, Kirsebom F,. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med. 2022; 386(16): 1532- 1546. doi: 10.1056/NEJMoa2119451 35249272 PMC8908811 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The authors elected not to use an extended Cox model because daily time steps were used and the rates were low enough that an extended Cox model would be approximately the same as a binomial model with log link.

    “We elected not to use an extended Cox model since daily time steps were used in the analysis and because the rates were low enough that an extended Cox model would be approximately the same as a binomial model with log link.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Observational data from Israel demonstrated waning of mRNA booster protection against infection.

    “Observational data from Israel demonstrated waning of mRNA booster protection against infection.6”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Patalon T, Saciuk Y, Peretz A,. Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine. Nat Commun. 2022; 13(1): 3203. doi: 10.1038/s41467-022-30884-6 35680872 PMC9184525 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The study did not have data on symptoms and hence was not able to analyze the association of vaccination with symptomatic disease.

    “We did not have data on symptoms and hence were not able to analyze the association of vaccination with symptomatic disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Epidemiologic studies from the UK and Qatar found that vaccine effectiveness against BA.1 and BA.2 infection were comparable.

    “Epidemiologic studies from the UK and Qatar found that vaccine effectiveness against BA.1 and BA.2 infection were comparable.31,32”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] Chemaitelly H, Ayoub HH, AlMukdad S,. Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar. Nat Commun. 2022; 13(1): 3082. doi: 10.1038/s41467-022-30895-3 35654888 PMC9163167

      Not checked in the free run.

    • cites [32] Kirsebom FCM, Andrews N, Stowe J,. COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England. Lancet Infect Dis. 2022; 22(7): 931- 933. doi: 10.1016/S1473-3099(22)00309-7 35623379 PMC9129256

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    These vaccine mandates did not differentiate between 2-dose and 3-dose mRNA vaccine recipients.

    “However, these vaccine mandates did not differentiate between 2-dose and 3-dose mRNA vaccine recipients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    There was no difference in nationally recommended testing protocols between 2-dose and boosted individuals.

    “There was no difference in nationally recommended testing protocols between 2-dose and boosted individuals.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There was no difference in nationally recommended testing protocols between 2-dose and boosted individuals.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    As comorbidities are associated with higher age, controlling for age would be expected to account for, at least partially, for the effects of comorbidities.

    “As comorbidities are associated with higher age, controlling for age would be expected to account for, at least partially, for the effects of comorbidities.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Comorbidities are associated with higher age.

  • May combine two claims.

    Study design and conductnone given

    Individuals with COVID-19 who developed severe disease after March 10, 2022, would be misclassified as nonsevere and this would be expected to affect those who were diagnosed close to the end of the study period.

    “Individuals with COVID-19 who developed severe disease after March 10, 2022, would be misclassified as nonsevere and this would be expected to affect those who were diagnosed close to the end of the study period.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Individuals with COVID-19 who developed severe disease after March 10, 2022, would be misclassified as nonsevere.
23 of 23

  • The paper relies on this without support.

    Notified SARS-CoV-2 infections recorded in the Singapore Ministry of Health database accurately reflect the incidence of SARS-CoV-2 infection in the study population.

    “We examined the outcomes of notified SARS-CoV-2 infection and severe COVID-19.”

  • The paper relies on this without support.

    After adjustment for age, sex, housing status, and calendar day, there is no unmeasured confounding of the association between vaccination status and SARS-CoV-2 infection or severe COVID-19.

    “The covariates examined for SARS-CoV-2 infection and severe COVID-19 were mRNA and inactivated COVID-19 vaccination status, as well as number of days since second or third dose controlling for age (categorized in 10-year intervals between ages 30 and 39, 40 and 49, 50 and 59, 60 and 69, 70 and 79, 80 years and older), sex, housing status (as a surrogate for socioeconomic status) and calendar day (”

  • The paper relies on this without support.

    Individuals who do not seek testing at registered sites are of lower medical risk.

    “Because individuals who do not seek testing at registered sites would be expected to be of lower medical risk”

  • The paper relies on this without support.

    Comorbidities are associated with higher age.

    “As comorbidities are associated with higher age”

  • The paper relies on this without support.

    Vaccine mandates enforced workplace and movement restrictions on individuals not meeting definitions for full vaccination.

    “Vaccine mandates enforced workplace and movement restrictions on individuals not meeting definitions for full vaccination”

  • The paper relies on this without support.

    There was no difference in nationally recommended testing protocols between 2-dose and boosted individuals.

    “There was no difference in nationally recommended testing protocols between 2-dose and boosted individuals.”

  • The paper relies on this without support.

    Individuals with COVID-19 who developed severe disease after March 10, 2022, would be misclassified as nonsevere.

    “Individuals with COVID-19 who developed severe disease after March 10, 2022, would be misclassified as nonsevere”

  • The paper relies on this without support.

    Vaccine-differentiated measures would bias the comparison between vaccinated and unvaccinated individuals.

    “As there were vaccine-differentiated measures that would bias the comparison between vaccinated and unvaccinated individuals”
8 of 8

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?

  • Boosting by BNT162b2 or CoronaVac restores strong protection against hospitalization and death, but the incremental effectiveness of BNT162b2 boosters against such outcomes waned over 4-6 months for adults and the elderly.

    “Further, although boosting by BNT162b2 or CoronaVac restores strong protection against hospitalization and death33–35, the incremental effectiveness of BNT162b2 boosters against such outcomes waned over the course of 4–6 months34 for both adults and the elderly36.”

    From Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population (2023) · cites this paper as [35]

    The citation is attached specifically to the claim that BNT162b2 booster effectiveness against hospitalization and death waned over 4–6 months. The Results (mRNA Vaccine Protection Against Severe COVID-19) report no significant decline in booster effectiveness against severe COVID-19 over time, and the Discussion says no waning was observed up to six months. The paper reports waning against confirmed infection instead. (LLM, conf=0.94)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

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.

  • Reinfection exclusion date falls after the study ended

    Minor

    The stated exclusion of anyone infected before December 27, 2022, would remove every infection observed during the study, which ended on March 10, 2022. The date also conflicts with the earlier stated exclusion of infections before December 27, 2021.

1 of 1

Cites

Flagged first, then by citations

1 of the 17 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Ng, O. T., Marimuthu, K., Lim, N., Lim, Z. Q., Thevasagayam, N. M., Koh, V., Chiew, C. J., Ma, S., Koh, M., Low, P. Y., Tan, S. B., Ho, J., Maurer-Stroh, S., Lee, V. J. M., Leo, Y.-S., Tan, K. B., Cook, A. R., & Tan, C. C.
Affiliations
  • Nanyang Technological University (SG)
  • National University of Singapore (SG)
  • Tan Tock Seng Hospital (SG)
  • Ministry of Health (SG)
  • Agency for Science, Technology and Research (SG)
  • National Centre for Infectious Diseases, Singapore
Corresponding author
  • Ng, Oon Tek
  • Tan, Chorh Chuan
ORCID
Venue
JAMA Network Open
Publisher
American Medical Association (AMA)
Published
2022-08-26
Volume
5
Issue
8
Pages
e2228900
ISSN
2574-3805 (ISSN-L)
DOI
10.1001/jamanetworkopen.2022.28900
PMC
PMC9419014
OpenAlex
W4293124974
Cited by
68
References
17
Citations by year
2026: 3 · 2025: 5 · 2024: 26 · 2023: 30 · 2022: 4
FWCI
7.93
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • JAMA Network Open (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
Funders
  • Medical Research Council (COVID-19)
  • National Medical Research Council (CGAug16C005, MOH-CIRG18Nov-0034, MOH-000469, CG21APR2005, MOH-000276)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Keywords
COVID-19 pandemic, SARS-CoV-2, mRNA vaccines, inactivated vaccine, BNT162b2, Moderna mRNA-1273, Omicron variant, severe COVID-19
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, BNT162 Vaccine, Aged, Female, Humans, Male, Middle Aged, RNA, Messenger, Singapore, Vaccines, Synthetic, Viral Vaccines, Cohort Studies, Incidence

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review