Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

Tenforde, Mark W; Self, Wesley H.; Adams, Katherine; 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; Henning, Daniel J.; Steingrub, Jay S.; Peltan, Ithan D.; Brown, Samuel M.; Martin, Emily T.; Monto, Arnold S.; Khan, Akram; Hough, Catherine L.; Busse, Laurence W.; Lohuis, Caitlin C. ten; 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; Chappell, James D.; Lauring, Adam S.; Grijalva, Carlos G; Rice, Todd W.; Jones, Ian D.; Stubblefield, William B; Baughman, Adrienne; Womack, Kelsey N.; Rhoads, Jillian P.; Lindsell, Christopher J.; Hart, Kimberly W.; Zhu, Yuwei; Olson, Samantha M; Kobayashi, Miwako; Verani, Jennifer R.; Patel, Manish; Influenza,

doi:10.1001/jama.2021.19499

Cited by 477 publications

(405 citation statements)

References 35 publications

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“…Previous data have shown that vaccination is associated with significant reduction in risk of hospitalisation and disease progression to death or mechanical ventilation in individuals with COVID-19. 12,33 Our data similarly showed a trend towards fewer hospital presentations. A later analysis during the UK's third wave will be useful here.…”

Section: Discussionsupporting

confidence: 68%

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

Kläser

Molteni

Graham

et al. 2021

Preprint

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BackgroundThe Delta (B.1.617.2) variant became the predominant UK circulating SARS-CoV-2 strain in May 2021. How Delta infection compares with previous variants is unknown.MethodsThis prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period.Findings3,581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta vs. Alpha infection (including fever, sore throat and headache) and vice versa (dyspnoea). Symptom burden in the first week was higher with Delta vs. Alpha infection; however, the odds of any given symptom lasting ≥7 days was either lower or unchanged. Illness duration ≥28 days was lower with Delta vs. Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1·47) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly (69-84%) reduced risk of Delta infection.InterpretationCOVID-19 from Delta or Alpha infections is clinically similar. The Delta variant is more transmissible than Alpha; however, current vaccines show good efficacy against disease.FundingUK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, Alzheimer’s Society, and ZOE Limited.Research in contextEvidence before this studyTo identify existing evidence for differences (including illness, transmissibility, and vaccine effectiveness) from SARS-CoV-2 infection due to Alpha (B.1.1.7) and Delta (B.1.617.2) variants, we searched PubMed for peer-reviewed articles and medRxiv for preprint publications between March 1 and November 18, 2021 using keywords (“SARS-CoV-2” OR “COVID-19”) AND (“delta variant” OR “B.1.617.2”) AND (symptom* OR transmiss* OR “disease duration” OR “illness duration” OR “symptom* duration”). Searches were not restricted by language. Among 169 identified PubMed articles, we found evidence that Delta variant has increased replication capacity (from 4-fold, up to 21-fold, compared with wild-type) and greater transmissibility (estimated between +20% and +97%), compared with previous strains. Currently available vaccines may have 2- to 5-fold lower neutralizing response to Delta vs. previous variants, depending on vaccine formulation, although their protective effect against severe disease and death appears to remain strong. REACT-1 study found that in UK infections were increasing exponentially in the 5-17-year old children in September 2021, coinciding with the start of the autumn school term in England. This was interpreted as an effect of the relatively low rate of vaccinated individuals in this age group. Other studies found that in unvaccinated individuals, Delta variant may be associated with higher odds of pneumonia, oxygen requirement, emergency care requests, ICU admission, and death. In a study of 27 (mainly young) cases, 22 persons were symptomatic, with fever (41%), cough (33%), headache (26%), and sore throat (26%) the commonest symptoms. We found no studies, beyond case series, investigating symptom and/or illness duration due to Delta variant infection otherwise.Added value of this studyUsing data from one of the largest UK citizen science epidemiological initiatives, we describe and compare illness (symptom duration, burden, profile, risk of long illness, and hospital attendance) in symptomatic community-based adults presenting when either the Alpha or Delta variant was the predominant circulating strain of SARS-CoV-2 in the UK. We assess evidence of transmission, reinfection, and vaccine effectiveness. Our data show that the seven most common symptoms with Delta infection were the same as with Alpha infection. Risks of illness duration ≥7 days and ≥28 days, and of requiring hospital care, were not increased. In line with previous research, we found increased transmissibility of Delta vs. previous variants; and no evidence of increased re-infection rates. Our data support high vaccine efficacy of BNT162b2 and ChAdOx1 nCoV-19 formulations against Delta variant infection. Overall, our study adds quantitative information regarding meaningful clinical differences in COVID-19 due to Delta vs. other variants.Implications of all the available evidenceOur observational data confirm that COVID-19 disease in UK in adults is generally comparable to infection with the Alpha variant, including in elderly individuals. Our data contribute to epidemiological surveillance from the wider UK population and may capture information from COVID-19 presentation within the community that might be missed in healthcare-based surveillance. Our data may be useful in informing healthcare service planning, vaccination policies, and measures for social protection.

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Section: Discussionsupporting

confidence: 68%

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

Kläser

Molteni

Graham

et al. 2021

Preprint

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“…In spite of this, taking into account the high number of cases naturally exposed to the virus and the high vaccination rate in the UK [57], as would be anticipated from our results, the daily deaths were a tenth of what they were in the prior wave [56,58]. Considering our findings and those from other groups [13][14][15]18,21], a more challenging scenario would be a predominance of other variants such as Alpha, Beta, Gamma or Kappa, showing limited neutralization after full vaccination with the mRNA COVID-19 vaccines. These results warrant further follow-up by public health institutions and officials to develop a preparedness plan in anticipation of the predominance of less effectively controlled variants.…”

Section: Discussionsupporting

confidence: 43%

“…The recent surge in cases despite extensive vaccination campaigns supports the concern about low vaccine effectiveness against variants. Studies are at odds regarding this topic, with some claiming that breakthrough infections are more likely to occur due to viral escape from antibodies [11,12]; others have demonstrated that mRNA vaccines remain effective through limiting COVID-19 severity, hospitalization and deaths [13][14][15][16][17][18][19][20][21]. Recently, more studies are exploring the efficacy of the natural immune response to SARS-CoV-2 vs. the mRNA vaccine-elicited response [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

Sariol

Serrano-Collazo

Ortiz

et al. 2021

Viruses

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The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.

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“…It has been well demonstrated that communities with higher levels of vaccination have lower rates of hospital admission and that once hospitalized, patients who are vaccinated are less likely to die during their hospitalization. [14] , [15] It would be interesting to determine whether increasing community rates of vaccination may serve as an intervention that could improve outcomes from COVID-19 IHCA, and yet another compelling reason to bolster vaccination efforts.…”

Section: Introductionmentioning

confidence: 99%

In-hospital cardiac arrest during the COVID-19 pandemic: Where do we go now?

2022

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Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

Cited by 477 publications

References 35 publications

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

In-hospital cardiac arrest during the COVID-19 pandemic: Where do we go now?

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