Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination - 24 U.S. Jurisdictions, October 3, 2021-December 24, 2022.

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks-2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6-8 (RR = 4.6), 9-11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks-2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.

COVID-19 vaccine uptake among Arkansas public K-12 school teachers and staff.

In December 2020, the first coronavirus disease 2019 (COVID-19) vaccines received emergency use authorization from the Food and Drug Administration (FDA). To strategically allocate the limited availability of COVID-19 vaccines, the Advisory Committee on Immunization Practices (ACIP) developed a phased approach for eligibility that prioritized certain population groups that were more vulnerable to infection and severe outcomes. Public K-12 teachers and staff were included in Phase 1b. The Arkansas Department of Health (ADH) sought to evaluate the uptake of COVID-19 vaccines within this priority group. In partnership with the Arkansas Department of Education (ADE), ADH received a list of 66,076 certified staff, classified staff, and teachers within the public K-12 school system. This list was matched to the state immunization registry via deterministic methods across three identifiers: first name, last name and date of birth. Uptake was assessed and the population was characterized using descriptive analyses. After 13 weeks of availability, 34,783 (51.2 %) of public K-12 teachers and staff had received at least one dose and 29,870 (44.0 %) had completed the series. School districts with the least robust uptake of COVID-19 vaccines tended to be in more rural areas, with some districts having less than 10 % of teachers and staff with at least one dose. The proportion of public K-12 teachers and staff with at least one dose of any COVID-19 vaccine grew quickly between January 18th and February 14th (4 % to 43 %) but has plateaued in the most recent seven weeks (45 % to 51 %). Although not directly measured, it is possible that vaccine hesitancy could be a factor in the attenuated uptake of COVID-19 vaccines within certain factions of the Arkansas public K-12 teacher and staff population. Overcoming vaccine hesitancy during the COVID-19 vaccine rollout will be critical in bringing an end to the pandemic.

Resource Savings Associated With Use of an Automated Symptom Monitoring Tool for COVID-19 Public Health Response, Summer 2020-Summer 2021.

CONTEXT: Active symptom monitoring is a key component of the public health response to COVID-19, but these activities are resource-intensive. Digital tools can help reduce the burden of staff time required for active symptom monitoring by automating routine outreach activities. PROGRAM: Sara Alert is an open-source, Web-based automated symptom monitoring tool launched in April 2020 to support state, tribal, local, and territorial jurisdictions in their symptom monitoring efforts. IMPLEMENTATION: As of October 2021, a total of 23 public health jurisdictions in the United States had used Sara Alert to perform daily symptom monitoring for more than 6.1 million individuals. This analysis estimates staff time and cost saved in 3 jurisdictions that used Sara Alert as part of their COVID-19 response, across 2 use cases: monitoring of close contacts exposed to COVID-19 (Arkansas; Fairfax County, Virginia), and traveler monitoring (Puerto Rico). EVALUATION: A model-based approach was used to estimate the additional staff resources that would have been required to perform the active symptom monitoring automated by Sara Alert, if monitoring instead relied on traditional methods such as telephone outreach. Arkansas monitored 283 705 individuals over a 10-month study period, generating estimated savings of 61.9 to 100.6 full-time equivalent (FTE) staff, or $2 798 922 to $4 548 249. Fairfax County monitored 63 989 individuals over a 13-month study period, for an estimated savings of 24.8 to 41.4 FTEs, or $2 826 939 to $4 711 566. In Puerto Rico, where Sara Alert was used to monitor 2 631 306 travelers over the 11-month study period, estimated resource savings were 849 to 1698 FTEs, or $26 243 161 to $52 486 322. DISCUSSION: Automated symptom monitoring helped reduce the staff time required for active symptom monitoring activities. Jurisdictions reported that this efficiency supported a rapid and comprehensive COVID-19 response even when experiencing challenges with quickly scaling up their public health workforce.

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.

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Association of the COVID-19 pandemic and dying at home due to ischemic heart disease.

The coronavirus disease 2019 (COVID-19) pandemic has been associated with a declining volume of patients seen in the emergency department. Despite the need for seeking urgent care for conditions such as myocardial infarction, many people may not seek treatment. This study seeks to measure associations between the COVID-19 pandemic and location of death among individuals who died from ischemic heart disease (IHD). Data obtained from death certificates from the Arkansas Department of Health was used to conduct a difference-in-difference analysis to assess whether decedents of IHD were more likely to die at home during the pandemic (March 2020 through September 2020). The analysis compared location of death for decedents of IHD pre and during the pandemic to location of death for decedents from non-natural causes. Before the pandemic, 50.0% of decedents of IHD died at home compared to 57.9% dying at home during (through September 2020) the pandemic study period (p < .001). There was no difference in the proportion of decedents who died at home from non-natural causes before and during the pandemic study period (55.8% vs. 53.5%; p = .21). After controlling for confounders, there was a 48% increase in the odds of dying at home from IHD during the pandemic study period (p < .001) relative to the change in dying at home due to non-natural causes. During the study period, there was an increase in the proportion of decedents who died at home due to IHD. Despite the ongoing pandemic, practitioners should emphasize the need to seek urgent care during an emergency.

Multidisciplinary Community-Based Investigation of a COVID-19 Outbreak Among Marshallese and Hispanic/Latino Communities - Benton and Washington Counties, Arkansas, March-June 2020.

By June 2020, Marshallese and Hispanic or Latino (Hispanic) persons in Benton and Washington counties of Arkansas had received a disproportionately high number of diagnoses of coronavirus disease 2019 (COVID-19). Despite representing approximately 19% of these counties' populations (1), Marshallese and Hispanic persons accounted for 64% of COVID-19 cases and 57% of COVID-19-associated deaths. Analyses of surveillance data, focus group discussions, and key-informant interviews were conducted to identify challenges and propose strategies for interrupting transmission of SARS-CoV-2, the virus that causes COVID-19. Challenges included limited native-language health messaging, high household occupancy, high employment rate in the poultry processing industry, mistrust of the medical system, and changing COVID-19 guidance. Reducing the COVID-19 incidence among communities that suffer disproportionately from COVID-19 requires strengthening the coordination of public health, health care, and community stakeholders to provide culturally and linguistically tailored public health education, community-based prevention activities, case management, care navigation, and service linkage.

Characteristics of E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) Patients.

During August-December 2019, 23 persons who received a diagnosis of e-cigarette, or vaping, product use-associated lung injury (EVALI) were reported to the Arkansas Department of Health (ADH); none died. Among Arkansas EVALI patients, most were aged <25 years and white; two-thirds were male. Approximately half of Arkansas EVALI patients were admitted to intensive care units. Among 18 patients who were interviewed, 61% reported using both nicotine and tetrahydrocannabinol in an e-cigarette, or vaping, device during the 90 days preceding illness onset. Clinicians should remain vigilant for EVALI and continue to report cases to ADH.

History and impact of nutritional epidemiology.

The real and important role of epidemiology was discussed, noting heretofore unknown associations that led to improved understanding of the cause and prevention of individual nutritional deficiencies. However, epidemiology has been less successful in linking individual nutrients to the cause of chronic diseases, such as cancer and cardiovascular disease. Dietary changes, such as decreasing caloric intake to prevent cancer and the Mediterranean diet to prevent diabetes, were confirmed as successful approaches to modifying the incidence of chronic diseases. The role of the epidemiologist was confirmed as a collaborator, not an isolated expert of last resort. The challenge for the future is to decide which epidemiologic methods and study designs are most useful in studying chronic disease, then to determine which associations and the hypotheses derived from them are especially strong and worthy of pursuit, and finally to design randomized studies that are feasible, affordable, and likely to result in confirmation or refutation of these hypotheses.

Vitamin/trace mineral supplements for the elderly.

The fraction of population that is elderly has been increasing, as has the consumption of vitamin/trace mineral supplements, which is now a multibillion dollar industry. Yet the rationale for such supplement intake by the majority may be questioned. Some of the current recommendations for micronutrient intake by the elderly are extrapolations from recommendations made for younger adults, whereas other recommendations are based on measurements of biochemical indices not proven to reflect a deficient level in the elderly. Suggestions that the elderly need more than the recommended daily allowances largely rest on the assumption that they should have biochemical indices similar to younger adults despite decreased energy intake with decreased physical and metabolic activities of the elderly. Although some individuals require supplementation because of problems with intake, absorption, or metabolism, there is little or no proof that boosting micronutrient intake above what can be achieved in well-balanced diets, some of which already contain fortified foods, will lead to a healthier outcome for most elderly individuals. There is not only the potential for unnecessary and occasionally harmful excess administered to some, but there is a cost that now runs in the billions of dollars and adds to the costs of covering multiple chronic disease conditions. Hence, some caution should be exercised in public health promulgations concerning routine use of supplements for those in this age group (>65 y of age) and of both sexes until more research establishes clear connections between the need for micronutrients and nutrient-related health in the elderly.

Vitamin/mineral supplements: of questionable benefit for the general population.

In the United States today, there is a multibillion dollar industry in dietary supplements with at least a third sold as vitamin/mineral pills and drinks. Though everyone requires small amounts of these essential micronutrients, and supplements are of benefit to some within the population, the considerable majority of people can fulfill their needs with the intake of healthy diets of mixed foods. In addition, the fortification of some processed foods adds extra amounts of several micronutrients, especially those for which there is deemed to be a need in special segments of our population. In spite of this safe and adequate level of intake, there are many who have been led to believe that the frequent ingestion of supplements will be helpful in their efforts to maintain optimal health, live longer, and even prevent or cure non-deficiency diseases. It is the intent of this article to unravel the causes and misconceptions behind this practice and to emphasize that most of the money spent on unnecessary supplementation could be better used for other purposes.

On becoming a nutritional biochemist.

Much of the science underlying nutrition has come from biochemical studies. This certainly is true in our understanding of the metabolism and function of such micronutrient cofactors as vitamins and metal ions. My own interest stems from an early desire to understand the molecular events in an organism and ultimately to know the fate of those nutrients that are needed to maintain life. My training in chemistry, biochemistry, and nutrition was helpful in gaining knowledge about the interface among these disciplines. My interests followed an understandable trail, beginning with those factors that cause plant galls and continuing through carbohydrate metabolism to vitamins. After all, from studying such pentitols as ribitol with Professor Touster at Vanderbilt University through indoctrination with enzymes, vitamins, and coenzymes with Professor Snell at the University of California-Berkeley, it was rational to begin my independent academic life investigating the enzymes that convert a ribityl-containing vitamin, namely riboflavin, to its operational flavocoenzymes. While at Cornell University, I encountered Professor Wright, who shared an interest in biotin. My realization that there was a similar need to determine the metabolism of lipoate followed logically. Interactions with inorganic chemists such as Professor Sigel at Basel University, as well as inorganic chemists at Cornell, led to an interest in metal ions. As summarized in this article, my colleagues and I are pleased to have contributed to both basic knowledge about cofactors and to have utilized much of this information in extensions to applications. Along the way, I have served by teaching, researching, and administrating at the universities that provided my positions in academe, and I have worked to share the load of numerous public and professional duties that are summarized herein. Altogether it has been an enjoyable career to be a nutritional biochemist. I recommend it for those who follow.

Micronutrient cofactor research with extensions to applications.

Following identification of essential micronutrients, there has been a continuum of research aimed at revealing their absorption, transport, utilization as cofactors, and excretion and secretion. Among those cases that have received our attention are vitamin B6, riboflavin, biotin, lipoate, ascorbate, and certain metal ions. Circulatory transport and cellular uptake of the water-soluble vitamins exhibit relative specificity and facilitated mechanisms at physiological concentrations. Isolation of enzymes and metabolites from micro-organisms and mammals has provided information on pathways involved in cofactor formation and metabolism. Kinases catalysing phosphorylation of B6 and riboflavin have a preference for Zn2+ in stereospecific chelates with adenosine triphosphate. The synthetase for flavin adenine dinucleotide prefers Mg2+. The flavin mononucleotide-dependent oxidase that converts the 5'-phosphates of pyridoxine and of pyridoxamine to pyridoxal phosphate is a connection between B6 and riboflavin and is a primary control point for conversion of B6 to its coenzyme. Sequencing and cloning of a side-chain oxidase for riboflavin was achieved. Details on binding and function have been delineated for some cofactor systems, especially in several flavoproteins. There is both photochemical oxidation and oxidative catabolism of B6 and riboflavin. Both biotin and lipoate undergo oxidation of their acid side chains with redox cleavage of the rings. Applications from our findings include the development of affinity absorbents, enhanced drug delivery, delineation of residues in biopolymer modification, pathogen photoinactivation in blood components, and input into human dietary recommendations. Ongoing and future research in the cofactor arena can be expected to add to this panoply. At the molecular level, the way in which the same cofactor can participate in diverse catalytic reactions resides in interactions with surrounding enzyme structures that must be determined case by case. At the level of human intake, more knowledge is desirable for making micronutrient recommendations based on biochemical indicators, especially for the span between infancy and adulthood.