1. mRNA vaccines highly effective at preventing death from COVID-19, less effective at preventing infection
Abstract: https://www.acpjournals.org/doi/10.7326/M21-3256
URL goes live when the embargo lifts
A target trial emulation study found that in an elderly population of U.S. veterans with high comorbidity burden, mRNA vaccine efficacy at preventing infection with COVID-19 was substantially lower than previously reported but effectiveness against death was very high. These finding suggest that complementary infection mitigation efforts remain important for pandemic control, even with vaccination. The study is published in Annals of Internal Medicine.
The real-world effectiveness of the Moderna or Pfizer-BioNTech COVID-19 mRNA vaccines in ethnically and racially diverse populations across the entire United States is not well characterized, especially in more vulnerable populations, such as elderly persons with high comorbidity burden. The U.S. Department of Veterans Affairs (VA) health care system is the largest national, comprehensive health care system in the United States. As such, it offers the opportunity to evaluate vaccines in this population.
Researchers from Veterans Affairs Puget Sound Health Care System and University of Washington School of Medicine designed an observational study to emulate a target trial of COVID-19 vaccination versus placebo. Of the more than 5 million people receiving care in the Veterans Affairs health care system, those who received at least 1 dose of the Moderna or Pfizer–BioNTech COVID-19 vaccine from 11 December 2020 to 25 March 2021 (n = 2,099,871) were matched to unvaccinated controls in a 1:1 ratio according to demographic, clinical, and geographic characteristics. The researchers found that vaccine effectiveness at 7 or more days after the second vaccine dose was 69% for SARS-CoV-2 infection and 86% for SARS-CoV-2–related death during follow-up extending to 30 June 2021. Vaccine effectiveness did not decline when follow-up was extended from 31 March to 30 June 2021. Vaccine effectiveness against SARS-CoV-2 infection decreased with increasing age and comorbidity burden. According to the researchers, these findings suggest that protection against infection from COVID-19, even among vaccinated individuals, will require continued attention to additional mitigation strategies.
Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, George N. Ioannou, BMBCh, MS, please contact Brian Donohue at bdonohue@uw.edu.
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2. Bamlanivimab may be effective for hospitalized patients with early SARS-CoV-2 and no detectable levels of endogenous neutralizing antibody
The neutralizing monoclonal antibody therapy may be harmful in patients who have already mounted an endogenous antibody response
Abstract: https://www.acpjournals.org/doi/10.7326/M21-3507
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A randomized controlled trial found that the neutralizing monoclonal antibody therapy Bamlanivimab may be effective for hospitalized patients with SARS-CoV-2 and no detectable levels of endogenous neutralizing antibody (nAb) at the time of administration. Conversely the therapy may be harmful in patients who have already mounted a nAb response. As such, it is critical to rapidly determine endogenous antibody status in hospitalized patients before administrating neutralizing monoclonal antibody products. The findings are published in Annals of Internal Medicine.
The ACTIV-3/TICO (Accelerating COVID-19 Therapeutic Interventions and Vaccines, Inpatient Monoclonal Antibodies and Other Therapies/Therapeutics for Inpatients With COVID-19) master protocol was set up in June and July 2020 to study the clinical effect and safety of novel antiviral agents against SARS-CoV-2 in patients admitted to hospital with COVID-19 within 12 days of symptom onset compared with placebo. To date, 6 novel investigational agents have been studied. The study of Bamlanivimab in ACTIV-3/TICO was stopped due to futility, meaning there was no evidence of clinical effect.
In the Bamlanivimab substudy of ACTIV-3/TICO 314 patients with SARS-CoV-2 were randomly assigned to receive either Bamlanivimab or placebo. The patients were followed for 90 days to determine response. At start of the trial, blood was collected from study participants and tested for the presence of endogenous nAb (i.e. the immune response that enables the host from eventually clearing the infection), and markers of ongoing viral replication (including a novel test for viral antigen levels in plasma) to evaluate the prespecified hypothesis that Bamlanivimab has greater benefit in patients without nAb at study entry than in those with antibodies, especially if viral levels are high. The researchers found that Bamlanivimab was clinically effective among those patients that had yet to mount an endogenous nAb response. Such patients typically have uncontrolled viral replication. As such, this finding supported the predetermined hypothesis. Bamlanivimab did not appear to be clinically effective in hospitalised patients that had already mounted an endogenous nAb response. In fact, the administration of exogenous monoclonal antibodies in these patients may actually cause net clinical harm and should be avoided, the researchers say. The mechanism for explaining the harm in these patients remains unclear, but is under active investigation within the ACTIV-3/TICO platform.
Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Jens D. Lundgren, MD, DMSc, please contact
Lisbeth Jørgensen at lisbeth.joergensen.04@regionh.dk.
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3. More than 7 million people became new gun owners between January 2019 and May 2021
New gun owners exposed 11 million people, including 5 million children, to the risks associated with household firearms
Abstract: https://www.acpjournals.org/doi/10.7326/M21-3423
URL goes live when the embargo lifts
An analysis of the 2021 National Firearm Survey found that firearm purchases accelerated in the U.S. during 2020-2021 compared to 2019, with more than 5 million adults becoming first-time gun owners between January 2020 and April 2021 compared to 2.4 million adults in 2019. Over the 2019-April 2021 time-period, these new gun owners newly exposed more than 11 million persons to household firearms, including more than 5 million children. Exposure to household firearms increases risk for suicide, homicide, and accidental firearm injury for all household members. The findings are published in Annals of Internal Medicine.
The U.S. does not track gun sales to civilians, but it does track the number of background checks performed by the Federal Bureau of Investigation (FBI) National Instant Criminal Background Check System (NICS), a metric that serves as a proxy for firearm sales. The surge in background checks recorded by the FBI starting in early 2020 marked an acceleration in gun purchases. NICS checks, however, do not provide information about the characteristics of those who purchased guns, how many guns they purchased, or whether, at the time of the purchase, they already owned guns or lived in a household with a gun.
Researchers from Northeastern University and the Harvard TH Chan School of Public Health studied data from the 2021 National Firearms Survey, a probability-based online survey of U.S. adults conducted 15 April 2021 to 26 April 2021, with a brief follow-up survey in May 2021, to estimate the number and characteristics of U.S. adults who purchased firearms during the study period, differentiating those who became new gun owners from those who did not, and juxtaposing these 2 groups with gun owners who had not recently purchased firearms and with gun owners as a whole. They found that the great majority of the 27 million adults who bought guns over the 28-month study period already owned firearms. Of the approximately 7.5 million who became new gun owners (2.9% of all US adults) between January 1, 2019 and April 26, 2021, most (5.4 million) had lived in homes without guns. Approximately half of all new gun owners were female and nearly half were people of color, a demographic distribution that was apparent in 2019 (i.e., prior to the pandemic). By contrast, other recent purchasers who were not new gun owners were predominantly male (70%) and White (74%), as were gun owners overall (63% male, 73% White).
According to the study authors, their findings suggest that the surge in NICS checks starting in early 2020, an increase superimposed on an upward trend apparent since 2005, was accompanied by a substantial increase in the number of U.S. adults who purchased firearms and the number of new gun owners created by those purchases, compared with 2019 statistics. The health consequences of the recent surge in personal and household gun ownership will be borne not only by the U.S. adults who have recently become new gun owners but also by the millions of others who live with them, including an estimated 5 million children who have been newly exposed to household firearms since 2019.
Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Matthew Miller, MD, MPH, ScD or Deborah Azrael, PhD, please contact Shannon Nargi at s.nargi@northeastern.edu or Todd Datz at tdatz@hsph.harvard.edu.
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4. Consider context when assessing COVID-19 vaccine efficacy over time
Data suggesting waning efficacy may suffer from risk heterogeneity
Abstract: https://www.acpjournals.org/doi/10.7326/M21-3609
URL goes live when the embargo lifts
A commentary from authors at the National Institute of Allergy and Infectious Diseases suggests that waning vaccine efficacy in the literature may be due to risk heterogeneity in study participants and not due to true diminishing efficacy in COVID-19 vaccines. The authors suggest that because the apparent waning efficacy of a vaccine in a study may be real or overstated based on changes in the population, individuals should assess the data critically and consider the context before drawing conclusions. The commentary is published in Annals of Internal Medicine.
Critical scientific questions about COVID-19 vaccines are whether the vaccine effect will wane over time, whether they will work on new variants, and whether booster shots are needed. The authors warn that when looking at the effect of vaccines over time, even when the population vaccine efficacy appears to be waning, that does not necessarily imply that the vaccine is working less effectively over time in each individual. They explain that it is possible that the populations are changing over time. Specifically, the proportion of disease-free individuals in the vaccinated and the unvaccinated populations is changing differentially, so that there will be lower proportions of high-risk individuals left in the unvaccinated population in later periods who did not have the disease in earlier periods. This differential change in populations happens when there is heterogeneity of risk in the populations and the vaccine is efficacious. This issue is known in the statistics literature as frailty effects or in the vaccine literature as depletion-of-susceptibles bias and should be considered when analyzing vaccine data.
Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Michael Fay, PhD, please contact the NIAID press office at niaidnews@niaid.nih.gov.
Journal
Annals of Internal Medicine
DOI
10.7326/M21-3256
Method of Research
Randomized controlled/clinical trial
Subject of Research
People
Article Title
COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System
Article Publication Date
21-Dec-2021