Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study
Open accessPublished version of a preprint
Abstract
Objectives: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design: Case-control study. Setting: 21 hospitals across the United States. Participants: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression. Results: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Real-world vaccine effectiveness studies during Delta and Omicron circulation showed less vaccine-induced protection against Omicron than against Delta.
“Real-word VE studies published during the periods of circulation of these two variants showed differences in vaccine-induced protection against Delta and Omicron variants-related infections, with less protection against Omicron than Delta [18-22].”
From Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France (2023) · cites this paper as [20]
The Results section reports lower two-dose mRNA vaccine effectiveness against COVID-19 hospital admission in the omicron period (65%) than in the delta period (85%). The citing sentence specifies protection against variant-related infections, but this study measured prevention of hospital admission, not infection generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLauring and colleagues estimated VE at 85% (95% CI: 83-87%) with 2 doses of any mRNA vaccine against Delta.
“In the USA, Lauring and colleagues estimated VE at 85% (95% CI: 83 87%) with 2 doses of any mRNA vaccine and 94% (95% CI: 92 95%) following the booster dose against Delta [20].”
Lauring and colleagues estimated VE at 94% (95% CI: 92-95%) following the booster dose against Delta.
“In the USA, Lauring and colleagues estimated VE at 85% (95% CI: 83 87%) with 2 doses of any mRNA vaccine and 94% (95% CI: 92 95%) following the booster dose against Delta [20].”
Our results were comparable to those from studies in other countries.
“Nevertheless our results were comparable to those from studies in other countries [19,20,34].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology
Rambaut, A., Holmes, E. C., O’Toole, Á., Hill, V., McCrone, J. T., Ruis, C., du Plessis, L., & Pybus, O. G. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0770-5 · Cited by 2,543 · see citing works
Genetic Variants of SARS-CoV-2—What Do They Mean?
Lauring, A. S., & Hodcroft, E. B. (2021) · JAMA · doi:10.1001/jama.2020.27124 · Cited by 604 · see citing works
Self-citationTenforde, M. W., Self, W. H., Naioti, E. A., Ginde, A. A., Douin, D. J., Olson, S. M., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., et al. (2021) · MMWR. Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7034e2 · Cited by 204 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 20
- [4]Sheikh A McMenamin J Taylor B Robertson C Public Health Scotland and the EAVE II Collaborators. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021; 397: 2461- 2. 10.1016/S0140-6736(21)01358-1. 34139198 PMC8201647 · DOI · Paper page
- [5]Twohig KA Nyberg T Zaidi A COVID-19 Genomics UK (COG-UK) consortium. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study. Lancet Infect Dis 2022; 22: 35- 42. 10.1016/S1473-3099(21)00475-8. 34461056 PMC8397301 · DOI · Paper page
- [6]Taylor CA Patel K Pham H COVID-NET Surveillance Team. Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1513- 9. 10.15585/mmwr.mm7043e1. 34710076 PMC8553023 · DOI
- [7]Viana R Moyo S Amoako DG. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature 2022; 7. 10.1038/s41586-022-04411-y. 35042229 PMC8942855 · DOI
- [8]Lewnard JA Hong VX Patel MM. Clinical outcomes among patients infected with Omicron (B.1.1.529) SARS-CoV-2 variant in southern California. medRxiv 2022; 01.11.22269045. 10.1101/2022.01.11.22269045. · DOI
- [9]Collie S Champion J Moultrie H Bekker LG Gray G. Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa. N Engl J Med 2022; 386: 494- 6. 10.1056/NEJMc2119270 34965358 PMC8757569 · DOI · Paper page
- [10]Johnson AG Amin AB Ali AR MSHI. COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021. MMWR Morb Mortal Wkly Rep 2022; 71: 132- 8. 10.15585/mmwr.mm7104e2. 35085223 PMC9351531 · DOI
- [11]Thompson MG Natarajan K Irving SA. Effectiveness of a Third Dose 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: 139- 45. 10.15585/mmwr.mm7104e3. 35085224 PMC9351525 · DOI · Paper page
- [13]Tenforde MW Self WH Adams K Influenza and Other Viruses in the Acutely Ill (IVY) Network. Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA 2021; 326: 2043- 54. 10.1001/jama.2021.19499. 34734975 PMC8569602 · DOI · Paper page
- [14]Tenforde MW Patel MM Ginde AA Tenforde MW Patel MM Ginde AA Influenza and Other Viruses in the Acutely Ill (IVY) Network. Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States. Clin Infect Dis 2021; ciab687. 10.1093/cid/ciab687. 34358310 PMC8436392 · DOI
- [15]Self WH Tenforde MW Rhoads JP IVY Network. Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions - United States, March-August 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1337- 43. 10.15585/mmwr.mm7038e1. 34555004 PMC8459899 · DOI · Paper page
- [16]Patel MK Bergeri I Bresee JS. Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization. Vaccine 2021; 39: 4013- 24. 10.1016/j.vaccine.2021.05.099. 34119350 PMC8166525 · DOI
- [17]Lewnard JA Patel MM Jewell NP. Theoretical Framework for Retrospective Studies of the Effectiveness of SARS-CoV-2 Vaccines. Epidemiology 2021; 32: 508- 17. 10.1097/EDE.0000000000001366. 34001753 PMC8168935 · DOI · Paper page
- [20]Tenforde MW Patel MM Gaglani M IVY Network. Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults - United States, August-December 2021. MMWR Morb Mortal Wkly Rep 2022; 71: 118- 24. 10.15585/mmwr.mm7104a2. 35085218 PMC9351530 · DOI
- [24]Marshall JC Murthy S Diaz J WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20: e192- 7. 10.1016/S1473-3099(20)30483-7. 32539990 PMC7292605 · DOI
- [26]Griffith GJ Morris TT Tudball MJ. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun 2020; 11: 5749. 10.1038/s41467-020-19478-2. 33184277 PMC7665028 · DOI · Paper page
- [27]Sullivan SG Tchetgen Tchetgen EJ Cowling BJ. Theoretical Basis of the Test-Negative Study Design for Assessment of Influenza Vaccine Effectiveness. Am J Epidemiol 2016; 184: 345- 53. 10.1093/aje/kww064. 27587721 PMC5013887 · DOI
- [28]Rufino J Baquero C Frey D. Using Survey Data to Estimate the Impact of the Omicron Variant on Vaccine Efficacy against COVID-19 Infection. Public and Global Health. medRxiv 2022. 10.1101/2022.01.21.22269636 PMC9844193 36650230 · DOI
- [29]Tseng HF Ackerson BK Luo Y. Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants. Nat Med 2022; published online 21 Feb. 35189624 PMC9117141
- [30]Young-Xu Y. Effectiveness of mRNA COVID-19 Vaccines against Omicron among Veterans. medRxiv 2022; 10.1101/2022.01.15.22269360. · DOI
Cited by
Sorted by citations
Gram, M. A., Emborg, H.-D., Schelde, A. B., Friis, N. U., Nielsen, K. F., Moustsen-Helms, I. R., Legarth, R., Lam, J. U. H., Chaine, M., Malik, A. Z., et al. (2022) · PLOS Medicine · doi:10.1371/journal.pmed.1003992 · Cited by 146 · see citing works
Au, W. Y., & Cheung, P. P.-H. (2022) · BMJ · doi:10.1136/bmj-2022-069989 · Cited by 143 · see citing works
Tseng, H. F., Ackerson, B. K., Bruxvoort, K. J., Sy, L. S., Tubert, J. E., Lee, G. S., Ku, J. H., Florea, A., Luo, Y., Qiu, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-35815-7 · Cited by 105 · see citing works
The Vaccine Efficacy Against the SARS-CoV-2 Omicron: A Systemic Review and Meta-Analysis
Zou, Y., Huang, D., Jiang, Q., Guo, Y., & Chen, C. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.940956 · Cited by 52 · see citing works
Self, W. H., Shotwell, M. S., Gibbs, K. W., de Wit, M., Files, D. C., Harkins, M., Hudock, K. M., Merck, L. H., Moskowitz, A., Apodaca, K. D., et al. (2023) · JAMA · doi:10.1001/jama.2023.3546 · Cited by 52 · see citing works
Tartof, S. Y., Slezak, J. M., Puzniak, L., Hong, V., Frankland, T. B., Xie, F., Ackerson, B. K., Valluri, S. R., Jodar, L., & McLaughlin, J. M. (2023) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(22)00354-x · Cited by 36 · see citing works
Song, S., Madewell, Z. J., Liu, M., Longini, I. M., & Yang, Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1195908 · Cited by 34 · see citing works
Pratama, N. R., Wafa, I. A., Budi, D. S., Sutanto, H., Asmarawati, T. P., Barlian Effendi, G., & Wungu, C. D. K. (2022) · Vaccines · doi:10.3390/vaccines10122180 · Cited by 30 · see citing works
Tamandjou Tchuem, C. R., Auvigne, V., Vaux, S., Montagnat, C., Paireau, J., Monnier Besnard, S., Gabet, A., Benhajkassen, N., Le Strat, Y., Parent Du Chatelet, I., et al. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.02.062 · Cited by 27 · see citing works
“In the USA, Lauring and colleagues estimated VE at 85% (95% CI: 83 87%) with 2 doses of any mRNA vaccine and 94% (95% CI: 92 95%) following the booster dose against Delta [20].”
Arashiro, T., Miwa, M., Nakagawa, H., Takamatsu, J., Oba, K., Fujimi, S., Kikuchi, H., Iwasawa, T., Kanbe, F., Oyama, K., et al. (2024) · Vaccine · doi:10.1016/j.vaccine.2023.12.033 · Cited by 11 · see citing works
Self-citation
- Authors
- Lauring, A. S., Tenforde, M. W., Chappell, J. D., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Exline, M. C., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Halasa, N., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Adams, K., Schrag, S. J., Olson, S. M., Kobayashi, M., Verani, J. R., Patel, M. M., & Self, W. H.
- Affiliations
- University of Michigan (US)
- Centers for Disease Control and Prevention (US)
- Vanderbilt University Medical Center (US)
- Baylor Scott & White Medical Center - Temple (US)
- University of Colorado Anschutz (US)
- University of Iowa (US)
- Beth Israel Deaconess Medical Center (US)
- Wake Forest University Health Sciences (US)
- Johns Hopkins University (US)
- Hennepin County Medical Center (US)
- The Ohio State University (US)
- Albert Einstein College of Medicine (US)
- University of Washington (US)
- Baystate Medical Center (US)
- University of Utah (US)
- Oregon Health & Science University (US)
- Emory University (US)
- Emory Critical Care Center, Emory Healthcare, Atlanta, GA, USA
- Cleveland Clinic (US)
- Stanford Medicine (US)
- University of California, Los Angeles (US)
- University of Miami (US)
- Washington University in St. Louis (US)
- Vanderbilt University (US)
- Corresponding author
- Self, Wesley H
- ORCID
- Lauring, Adam S
- Tenforde, Mark W
- Chappell, James D
- Gaglani, Manjusha
- Ginde, Adit A
- McNeal, Tresa
- Ghamande, Shekhar
- Douin, David J
- Talbot, H Keipp
- Casey, Jonathan D
- Mohr, Nicholas M
- Zepeski, Anne
- Shapiro, Nathan I
- Gibbs, Kevin W
- Files, D Clark
- Hager, David N
- Shehu, Arber
- Prekker, Matthew E
- Erickson, Heidi L
- Exline, Matthew C
- Gong, Michelle N
- Mohamed, Amira
- Johnson, Nicholas J
- Srinivasan, Vasisht
- Steingrub, Jay S
- Peltan, Ithan D
- Brown, Samuel M
- Martin, Emily T
- Monto, Arnold S
- Khan, Akram
- Hough, Catherine L
- Busse, Laurence W
- Duggal, Abhijit
- Wilson, Jennifer G
- Gordon, Alexandra June
- Qadir, Nida
- Chang, Steven Y
- Mallow, Christopher
- Rivas, Carolina
- Babcock, Hilary M
- Kwon, Jennie H
- Halasa, Natasha
- Grijalva, Carlos G
- Rice, Todd W
- Stubblefield, William B
- Womack, Kelsey N
- Rhoads, Jillian P
- Lindsell, Christopher J
- Hart, Kimberly W
- Zhu, Yuwei
- Adams, Katherine
- Schrag, Stephanie J
- Olson, Samantha M
- Kobayashi, Miwako
- Verani, Jennifer R
- Patel, Manish M
- Self, Wesley H
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2022-03-09
- Volume
- 376
- Pages
- e069761
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC8905308
- OpenAlex
- W4220907252
- Cited by
- 656
- References
- 3
- Citations by year
- 2026: 29 · 2025: 59 · 2024: 128 · 2023: 236 · 2022: 203 · 2021: 1
- FWCI
- 76.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ (publishedVersion, cc-by-nc)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- U.S. Department of Defense
- Abbott Laboratories
- Pfizer
- Sanofi
- Gilead Sciences
- Vanderbilt University (UL1‐TR002243)
- Brigham Young University
- Medpace
- United Therapeutics Corporation
- Cincinnati Children's Hospital Medical Center
- Intermountain Research and Medical Foundation
- Regeneron Pharmaceuticals
- Vanderbilt University Medical Center (UL1 TR002243)
- Incyte
- Marcus Foundation
- York University
- University of Oxford
- National Institutes of Health (TR002243, UL1TR002243)
- Centers for Disease Control and Prevention (75D30121F00002)
- Agency for Healthcare Research and Quality
- National Heart, Lung, and Blood Institute (K23HL153584, T32HL087738)
- National Institute of General Medical Sciences (K23GM129661, T32GM135169)
- National Institute of Allergy and Infectious Diseases (K24AI148459, K23AI137321)
- Agency for Toxic Substances and Disease Registry
- National Center for Advancing Translational Sciences (TR002243)
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2 variants, Omicron variant, Delta variant, Alpha variant, mRNA vaccines, vaccine effectiveness, hospitalization, disease severity, in-hospital mortality, WHO Clinical Progression Scale, test-negative design, booster vaccination, unvaccinated patients, hospitalized adults, United States, whole genome sequencing
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.
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
