COVID-19 Vaccination and Non-COVID-19 Mortality Risk - Seven Integrated Health Care Organizations, United States, December 14, 2020-July 31, 2021.

By September 21, 2021, an estimated 182 million persons in the United States were fully vaccinated against COVID-19.* Clinical trials indicate that Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Johnson & Johnson; Ad.26.COV2.S) vaccines are effective and generally well tolerated (1-3). However, daily vaccination rates have declined approximately 78% since April 13, 2021†; vaccine safety concerns have contributed to vaccine hesitancy (4). A cohort study of 19,625 nursing home residents found that those who received an mRNA vaccine (Pfizer-BioNTech or Moderna) had lower all-cause mortality than did unvaccinated residents (5), but no studies comparing mortality rates within the general population of vaccinated and unvaccinated persons have been conducted. To assess mortality not associated with COVID-19 (non-COVID-19 mortality) after COVID-19 vaccination in a general population setting, a cohort study was conducted during December 2020-July 2021 among approximately 11 million persons enrolled in seven Vaccine Safety Datalink (VSD) sites.§ After standardizing mortality rates by age and sex, this study found that COVID-19 vaccine recipients had lower non-COVID-19 mortality than did unvaccinated persons. After adjusting for demographic characteristics and VSD site, this study found that adjusted relative risk (aRR) of non-COVID-19 mortality for the Pfizer-BioNTech vaccine was 0.41 (95% confidence interval [CI] = 0.38-0.44) after dose 1 and 0.34 (95% CI = 0.33-0.36) after dose 2. The aRRs of non-COVID-19 mortality for the Moderna vaccine were 0.34 (95% CI = 0.32-0.37) after dose 1 and 0.31 (95% CI = 0.30-0.33) after dose 2. The aRR after receipt of the Janssen vaccine was 0.54 (95% CI = 0.49-0.59). There is no increased risk for mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the United States.

Estimated rates of influenza-associated outpatient visits during 2001-2010 in 6 US integrated healthcare delivery organizations.

BACKGROUND: Population-based estimates of influenza-associated outpatient visits including both pandemic and interpandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare. OBJECTIVE: To estimate influenza-associated outpatient visits in 6 US integrated healthcare delivery organizations enrolling ~7.7 million persons. METHODS: Using negative binomial regression methods, we modeled rates of influenza-associated visits with ICD-9-CM-coded pneumonia or acute respiratory outpatient visits during 2001-10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in 2 contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits. RESULTS: Outpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30-70) and 203 (95% CI, 180-240) per 10 000 person-years, respectively, for interpandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161-255) and 542 (95% CI, 441-823) per 10 000 person-years. During the pandemic, children aged 2-17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50-121] to 381 [95% CI, 366-481]). Rates estimated with pneumonia visits were consistent with rates of RT-PCR-confirmed influenza visits during 4 of 5 seasons in 1 comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude. CONCLUSIONS: Estimated rates of influenza-associated outpatient visits were higher in children than adults during pre-pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza-coded visits were similar to rates from studies using RT-PCR-confirmed influenza.

Vitamin E, vitamin A, and zinc status are not related to serologic response to influenza vaccine in older adults: an observational prospective cohort study.

It has been hypothesized that micronutrient levels play a role in the immune response to vaccination; however, population-level research on the association between micronutrient levels and immune response to influenza vaccination is needed. In this study, we hypothesized that decreasing levels of nutrients would be associated with decreased hemagglutination inhibition (HAI) responses to influenza vaccination. Therefore, the purpose of this study was to determine whether serum vitamin A, vitamin E, or zinc levels are associated with influenza vaccine response determined by HAI titer in adults 65 years or older. Participants in this study included 205 community-dwelling adults 65 years or older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009. Participants received trivalent influenza vaccine and donated blood samples before and 21 to 28 days after vaccination. Prevaccination levels of serum retinol, α-tocopherol, and zinc as well as prevaccination and postvaccination HAI titer levels were measured. No participants were vitamin A or vitamin E deficient; 20% had low serum zinc levels (<70 µg/dL). Continuous variables and categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not related to prevaccination or postvaccination seroprotection or seroconversion for any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after adjusting for age, sex, body mass index, and prevaccination HAI geometric mean titer. In conclusion, our study population showed no association between variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine response as measured by HAI in adults older than 65 years. Thus, associations between micronutrients and other measures of vaccine response, such as cell-mediated immune parameters, should also be explored.

Vitamin D is not associated with serologic response to influenza vaccine in adults over 50 years old.

Vitamin D deficiency has been implicated in risk of respiratory illness. We determined whether serum vitamin D levels are related to influenza vaccine response measured by hemagglutination antibody inhibition (HAI) titer in adults aged ≥50 years old. The study was a prospective cohort study conducted over two influenza seasons (fall 2008-spring 2009 and fall 2009-spring 2010) in Marshfield, WI and Nashville, TN including 1103 community-dwelling adult volunteers ≥50 years of age. Pre-vaccination levels of serum vitamin D and HAI titer levels pre- and 21-28 days post-influenza vaccination were measured. Seroprotection was defined as HAI ≥40; seroconversion was defined as ≥4-fold rise in HAI titers from pre- to post-vaccination. More than 25% of participants were vitamin D deficient (<25ng/mL). Vitamin D measured as a continuous variable was not related to pre- or post-vaccination seroprotection or seroconversion for any vaccine strain in any year. Vitamin D deficiency was associated with a greater frequency of post-vaccination seroprotection for seasonal H1N1 in the first year of the study, but was not related to seroprotection or seroconversion for any other strain in either year. No consistent association was found between vitamin D levels or vitamin D deficiency and serologic response to influenza vaccination in older adults. Cell-mediated immune parameters should also be explored in order to further investigate possible relationships between micronutrient status and influenza vaccine response.